Bg Dchtp 2015

Ths. Phm Th an Phng B mn m bo cht lng v an ton thc phm Khoa Cng ngh Thc phm Trng i hc Nha Trang

THC PHM

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NI DUNGCh 1. I CNG C CHT HC THC

PHM Ch 2. DNG THC CA CC CHT C

TRONG C TH Ch 3. NH HNG CA C CHT LN CC

C QUAN QUAN TRNG CA C TH Ch 4. TC DNG C CA C CHT THC

PHM LN C TH

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Ti liu hc tp

L Ngc T v cng s, 2006. c t hc v An ton thc phm, Nh xut bn Khoa hc v K thut, tp. H Ch Minh.

L Huy B, 2006. c hc mi trng c bn, Nh xut bn i hc Quc gia, tp. H Ch Minh.

Phillip L.Williams v Robert C. James v Stephen M. Roberts, 2000. Principles of Toxicology. JOHNWILEY & SONS, INC.

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Ti liu tham kho

S. S. Deshpande, 2002. Handbook of Food Toxicology, Marcel Dekker, INC.

Nguyn Th Thn, 2004. c cht trong thc phm, NXB Khoa hc v K thut.

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Websites tham kho

http://foodsafety.usu.edu http://www.fao.org http://www.FDA.gov http://www.who.int/foodsafety/codex http://www.agroviet.gov.vn http://www.tcvn.gov.vn http://www.vfa.gov.vn http://www.elsevier.com http://en.wikipedia.org

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CH 1. I CNG C CHT HC THC

PHM

I.1 Khi nim chung v c cht hcI.2 Vai tr ca c cht hc thc phmI.3 Phn loi c cht thc phmI.4 Cc yu t nh hng n c tnh ca c cht

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I.1. Khi nim chung v c cht hcnh ngha J.F. Borzelleca nh ngha: "c cht hc l ngnh hc

nghin cu v lng v cht cc tc ng bt li ca cc tc nhn ha hc, vt l, sinh hc ln h thng sinh hc ca sinh vt sng".

c cht hc v c t hc l hai khi nim tng i ging nhau. c t hc l khoa hc nghin cu v bn cht v c ch gy c ca cc cht n c th sng hoc n nhng h thng sinh hc khc. nh ngha ny cng bao hm c vic xc nh mc c v tn sut ca cc hiu ng c trong mi lin quan vi mc nhim c mt c th.

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I.1. Khi nim chung v c cht hcCht c (toxin, poisoning) ! Cht c trong thc phm l do cht ha hc hay

hp cht ha hc c trong nguyn liu, sn phm thc phm mt nng nht nh gy ng c cho ngi hay ng vt khi ngi hay ng vt s dng chng.

Cht c c th tn ti nhiu trng thi khc nhau, c hnh thnh v ln vo thc phm bng nhiu con ng khc nhau.

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I.1. Khi nim chung v c cht hcc tnh (toxicity) ! c tnh l kh nng gy c ca cht c. c tnh ca mt sn phm thc phm thng c

lin quan n nhng yu t sau: Tn sut a vo: n ung mt ln duy nht hay

lp li nhiu. Mc tn hi. Thi gian cn thit lm xut hin mt hiu ng c.

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I.1. Khi nim chung v c cht hc c lc l lng cht c trong nhng iu kin nht nh gy nh hng c hi hoc nhng bin i sinh hc c hi cho c th.

Liu lng gy c (dose): LD50 (lethal dose) l liu lng th nghim lm cht

50% s ng vt trn tng s c cho n nh nhau, n v mg/kg ng vt sng trn cn.

LC50 (lethal concentration) l nng gy cht 50% ng vt th nghim, n v mg/l dung dch ha cht, thng dng nh gi c tnh ca cht c dng lng ha tan trong nc sng, sui hay nng hi hoc bi trong mi trng khng kh nhim.

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I.1. Khi nim chung v c cht hc Mc c tnh: c tnh cp tnh (acute toxicity) ca mt cht c coi

nh l cc tc dng khng tt n c th ngi, ng vt mt cch t ngt, trong khong thi gian ngn di 24 gi, sau khi n ung phi thc n cha c t.

c tnh cp (subacute toxicity) l s biu hin r cc hiu ng c ca mt cht, sau khi ngi, ng vt n ung mt lng nht nh nhng thng xuyn gp phi, vi thi gian c xc nh, khong di 90 ngy.

c tnh mn tnh (chronic toxicity) l s biu hin kh r cc tc dng c ca mt cht sau khi n ung mt lng lp i lp li hng ngy trong mt thi gian ko di trn 90 ngy.

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I.1. Khi nim chung v c cht hc Mc c c xc nh:

Nhm I: rt c, LD50 < 100 mg/kg Nhm II: c cao, LD50 = 100 - 300 mg/kg Nhm III: c va, LD50 = 300 - 1000 mg/kg Nhm IV: t c, LD50 > 1000 mg/kg

n v c cht (TU: Toxicity Units) l i lng th hin lng cht c ca mu th vi sinh vt th nghim. Mt n v tnh tng ng vi mu pha long git cht 50% s lng sinh vt th nghim.

TU cng cao, EC50 cng thp th mi trng cng c hi!12

I.1. Khi nim chung v c cht hc Kh nng tn ti v chuyn ha c cht thc phm

trong c th sinh vt.

Cht c nhim

c cht thc phm

c t t nhinPh gia cht h

tr ch bin

Gim c tnh Tng c tnh

Tng phn cc, tng tnh thn nc

D bi tit

Gim phn cc, tng tnh a m

Kh bi tit

C th sinh vt

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I.2. Vai tr ca c cht hc thc phm

VAI TR

CH v sn xut nng nghip thc phm

CH v mi trng

CH v sn xut cng nghip thc phm

CH vi con ngi

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I.2. Vai tr ca c cht hc thc phm1. c cht hc v sn xut nng nghip TP Ngi nui trng, ngi ch bin, ngi tiu th

u c lin quan n mi mc ca c cht hc thc phm.

bo v ma mng, ngi ta s dng nhng hp cht ha hc ang c v tm ra nhng dn xut mi kim

sot s tng sinh ca cc sinh vt sng k sinh.

Nhng nu thuc dit cn trng l cn thit cho cy th ng thi cng l cht c ng gm cho chnh ngi ang ng dng v cho c ngi khng may n phi cc d cht ny vi liu lng ln hn liu lng cho php.

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I.2. Vai tr ca c cht hc thc phm2. c cht hc v mi trng Sn xut nng nghip v ch bin thc phm v ang lm nhim t trng, ngun nc, khng kh vi d lng thuc tr su, dit c, phn bn,... Cc cht nhim s tn ti trong thc phm m chng ta cn kim sot chng mc d lng cho php.

Sn xut cng nghip s lm mi trng nhim cc kim loi nng, cc cht kh c, cc hydrocacbon a vng,...

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I.2. Vai tr ca c cht hc thc phm3. c cht hc v sn xut cng nghip thc

phm Trong cng nghip thc phm, thc phm i hi

phi c m bo an ton t khi cn l nguyn liu ban u, bn thnh phm n khi tr thnh sn phm thc phm. Do vy, thc phm cn c ch trng n phng php bo qun.

Bo qun thc phm l bo qun chng sau khi thu hoch, trong qu trnh ct gi, trong qu trnh ch bin cng nh trong qu trnh phn phi, c th coi l mt s cn thit tuyt i.

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I.2. Vai tr ca c cht hc thc phm Cc phng php bo qun ph bin hin nay l

phng php s dng nhit (nng hay lnh), phng php k thut vt l, phng php ha hc.

Trong , phng php bo qun bng cht ha hc c vai tr rt quan trng, nh c tnh hiu qu cao v chi ph r.

Tuy nhin, vn v sinh an ton thc phm sau x l ha hc phi c trng tm v c nh gi tht k kh nng gy ng c thc phm.

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I.2. Vai tr ca c cht hc thc phm4. c cht hc vi con ngi

Ai l ngi chu trch nhim v thc phm an ton, khng c c cht?

Ngi ch bin hay ngi s dng thc phm ?

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I.2. Vai tr ca c cht hc thc phm Nhng nguy c ca cc cht c c ngun gc t

nhin, cc cht nhim trong thc phm l tng i, v con ngi c th kim sot c nhng nguy c bit.

Tuy nhin, nguy c khi hp th mt vi phn mi ca miligam thuc bo v thc vt hoc kim loi nng hoc c t c trong thc phm khc vi nguy c khi hp th mt nng lng ln calo di dng ng hay lipid

V vy, con ngi cn phi c thng tin y v cc nguy c c hi ca c cht khi tn ti trong thc phm.

Ngi ch bin phi c o c, tun theo lut php.

Ngi tiu dng phi chu trch nhim v sc khe ca mnh.

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I.3. Phn loi c cht thc phmC s phn loi da theo mc ch nghin cu, i

tng nghin cu: Phn loi theo nng - liu lng. Phn loi theo bn cht. Phn loi theo mi trng (t, nc, khng kh, sinh

quyn). Phn loi theo mc nguy him. Phn loi theo ngun gc c cht. Phn loi theo dng tn ti. Phn loi thng qua ng xm nhp v gy hi. Phn loi theo ngnh kinh t - x hi: c cht trong

nng nghip, cng nghip, y t, qun s, thc phm...!21

I.3. Phn loi c cht thc phmC s phn loi: ! Phn loi theo qui trnh cng ngh (dng nguyn

cht, dng ph gia, dng dung mi, dng cht thi...)

Phn loi theo tc dng sinh hc n thun (tc dng kch ng, tc dng gy ngt, d ng, ung th, t bin...)

Phn loi theo sinh hc h thng: gy c ln m thn kinh, ln c quan to mu; gy c ln gan, thn, cc c quan khc.

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Mt s phng php phn loi1. Phn loi theo nng v liu lng Hu ht cc nguyn t ha hc u hin din vi mt

nng thch hp trong mi trng. Chng l cc nguyn t c ch gp phn to nn v duy tr s sng trn tri t.

Tuy nhin, mt s trong chng l cc cht c tim tng. Ty theo mi i tng b tc ng m nng hay liu lng tng vt qua mt mc gii hn, th cc c cht tim tng ny s pht huy c tnh ca n ln vt tip xc.

Mt c cht c nng nh c a vo mi trng trong mt thi gian di s gy c cho cc i tng trong h sinh thi do kh nng c tch ly sinh hc.

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Mt s phng php phn loiPhn loi theo nng v liu lng: ! Nng nn l nng ca cc nguyn t sn c

trong mi trng t nhin khng gy nh hng xu n sc khe ca con ngi v sinh vt.

Nng cho php l nng dng khng ch cht c trong vic bo v sc khe cho ngi v sinh vt.

Trong mi trng t nhin c nhng cht th hin tnh c ngay khi tn ti dng nguyn thy ca n. Kh nng gy c ca loi c cht, c t ny tc dng vi bt k nng (liu lng) ln hay nh, tc l khng ph thuc vo nng hin din ca n.

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Mt s phng php phn loi2. Phn loi theo bn cht ha hc ca c cht 1. Tnh c ca cht c c bn cht ph thuc

vo nhiu yu t nhng quan trng nht l dng cu trc ha hc ca n:

Cht c dng hp cht hydrocarbon c tnh c t l thun vi s nguyn t carbon trong phn t.

Nhng cht v c c cng nguyn t th cht no c s nguyn t t hn s c hn.

2. S nguyn t halogen thay th hydro cng nhiu th cht cng c.

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Mt s phng php phn loi

3. c cht trung gian gia hai loi bn cht v liu lng

C nhng cht c th xp vo loi c cht nng - liu lng bi ch vi mt nng vt qu gii hn, n mi th hin tnh c.

Tuy nhin, cng c th xp n vo loi cht c bn cht v xt mt iu kin nht nh, n c th gy ri lon sinh l, tn thng cho c th nu thm nhp vo cc c quan ni tng.

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Mt s phng php phn loi4. Phn loi theo mc nguy him Mc nguy him ca mt loi c cht trn mt i

tng nghin cu xc nh thng c phn loi da theo gi tr LD50 (median lethal dose: liu lng gy cht 50% ng vt th nghim, n v mg/kg ng vt sng trn cn) hay LC50 (median lethal concentration: nng gy cht 50% ng vt th nghim, n v mg/l dung dch ha cht).

Mc nguy him ty thuc vo nhiu yu t, theo phn loi ca WHO, cc ha cht c mc nguy him ty theo dng tn ti v con ng xm nhp vo c th sinh vt th nghim.

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Mt s phng php phn loi Bng phn loi cht c theo mc nguy

him (Ngun: WHO, 1998)

!!

Cp c

LD

Qua ming Qua da

Th rn Th lng Th rn Th lng

c mnh c c trung bnh c t

< 5 5 - 50

50 - 500 > 500

< 20 20 - 200

200 - 2000 < 2000

< 10 10 - 100

100 - 1000

< 40 40 - 400

400 - 4000 > 4000

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Mt s phng php phn loi5. Phn loi theo ngun gc c cht c cht trong t nhin xut pht t nhiu ngun

gc khc nhau nh ngun gc sinh hc, ha hc, cht phng x... v chnh ngun gc ny s nh hng nhiu n c tnh ca chng.

1. c t sinh hc l cht c c sinh ra t vi sinh vt, thc vt, ng vt, l cc sn phm ca qu trnh phn hy ng, thc vt cht di tc dng ca vi sinh vt, qu trnh bin i gen, c t t cc loi nm, cn trng...

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Mt s phng php phn loi Phn loi theo ngun gc c cht:

2. c cht ha hc l cc cht c c ngun gc t ha cht, l sn phm ca cc phn ng ha hc, t cc ngnh cng nghip, cht thi cng nghip... c xp vo loi c cht ha hc. Mc gy c ca chng ty thuc nhiu vo cu trc ha hc, nng tc ng ca chng v trng thi ca c th nhn cht c.

3. Tia phng x l nhng tia mt thng khng nhn thy c, pht ra t cc nguyn t phng x nh uranium, cobalt, radium... Cht phng x xm nhp vo c th (qua ng h hp, tiu ha) ti cc c quan, gy tc dng chiu x gi l tc dng ni chiu. Tc dng ny nguy him hn tc dng ngoi chiu (l nh hng ca tia phng x khi chiu t ngoi vo b mt c th).!30

Mt s phng php phn loi6. Phn loi theo trng thi tn ti Trng thi ha hc ca cc cht c tn ti

dng n cht hay hp cht, dng ion hay phn t u c kh nng gy c v kh nng gy c khc nhau. Mi trng tn ti ha cht cng gp phn lm tng hay gim thiu c tnh. Hoc s hin din cng mt lc ca nhiu c t, c cht s lm cng hng tnh c hay lm trit tiu tnh c ca nhau.

Trng thi vt l ca c cht c th th rn, lng, kh, hi, bi... Mc gy c ca cht c tng dn t th rn sang lng v cao nht l th kh. Kh nng gy c thay i theo trng thi vt l ca c cht ph thuc vo mc khuch tn cc c cht vo mi trng. !31

Mt s phng php phn loi7. Phn loi thng qua ng thm nhp v gy

hi Cht c thm nhp vo cc i tng trong h

sinh thi bng nhiu con ng, cch thc khc nhau. Cc cch thc ny cng quyt nh n mc tc hi m c cht nh hng ln ng vt, thc vt v con ngi.

D bng con ng thm nhp no th khi vo trong c th sinh vt v con ngi, c cht cng gy ra s mt n nh ca cu trc vt cht trong c th.

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I.4. Cc yu t nh hng n c tnh ca c chtNgoi liu lng v thi gian nhim, cn c cc yu

t khc nh: !!!! Cc yu t sinh l Cc yu t vt l, Cc yu t mi trng, V cc yu t khc.

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I.4. Cc yu t nh hng n c tnh ca c cht

1. Liu lng v thi gian tip xc vi ha cht c

Liu lng tip xc cng cao v thi gian tip xc cng lu th tnh c c tc hi cng ln.

S hin din cng mt lc nhiu loi ha cht trong c th sng ti cng mt thi im tip xc l yu t tc ng n tnh c ca cc cht.

2. Cc yu t sinh hc Tui tc Tnh trng sc khe Loi v ging Yu t gen di truyn!34

I.4. Cc yu t nh hng n c tnh ca c cht3. Cc nhn t mi trng nh hng n hot

tnh ca c cht pH mi trng dn in Cc cht cn Nhit Din tch mt thong Cc cht i khng hoc xc tc Cc yu t v kh tng, thy vn Kh nng t lm sch ca mi trng

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CH 2. DNG THC CA CC CHT C TRONG C TH

II.1 Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phmII.2 S hp thu, phn phi v o thi cc cht c trong c thII.3

Chuyn ha sinh hc cc c t - s cn bng gia cht c hi v cht kh c

II.4 Tc dng c ln c th36

II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm

Trong qu trnh sinh trng v pht trin, mi c th sinh vt u c th b nh hng trc tip hoc gin tip ca c cht, c t qua dy chuyn thc phm (chui thc phm).

Cc thc vt bc thp, thc vt bc cao, ng vt bc thp, ng vt bc cao v k c con ngi, khi tip xc vi c cht, c t u c th b nhim c.

Khi xm nhp vo c th sinh vt, cht c s tri qua qu trnh chuyn ha sinh hc. Phn ln cc cht c c o thi ra ngoi, mt phn c th b lu gi v tch t li trong c th.

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II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm Qu trnh chuyn ha sinh hc trong c th sinh

vt

Kh hot ha (tng phn cc, tng tnh thn nc)

Hot ha (gim phn cc, tng tnh thn m)

c cht

v c t

D bi tit Gim c tnh

Tng c tnhKh bi tit

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II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm Dy chuyn thc phm l con ng chuyn

nng lng t c th sinh vt ny sang c th sinh vt khc.

Theo dy chuyn thc phm, cc cht c kh bi tit s c chuyn t sinh vt ny sang sinh vt khc v c tch ly hm lng c cht cao hn dn theo bc dinh dng v thi gian sng.

cQu trnh ny gi l qu trnh tch ly v phng i sinh hc ca c cht trong c th sinh vt.

cDo vy, hm lng c cht, c t bc dinh dng sau lun cao hn bc trc nhiu ln.

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II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm Dy chuyn thc phm (food chain) tng qut

Thc vt bc thp Thc vt bc cao

ng vt ph du

C nh

C ln

ng vt

Gip xc, nhuyn th

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II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm V d chui thc phm c trng

Food Chain in Nature

*P = producer, *H = herbivore, *C1 = carnivore order-1, *C2 = carnivore order-2)

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T c h ly s i n h hc (bioaccumulation) l mt qu trnh tch t cc nguyn t vi lng, cc cht nhim vo trong c th sinh vt thng qua qu trnh hp th bi cc sinh vt t mi trng xung quanh m chng ang sng.

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II.1. Qu trnh tch ly v chuyn ha sinh hc ca c cht qua chui thc phm i vi cc cht gy nhim thng qua chui

thc n, s nh hng biu hin r cc ng vt c mc tiu th cao hn (bao gm c con ngi). Kh nng khng ca sinh vt khc vi con ngi khi c tc ng ca cht c.

i vi bt k mt sinh vt no, s khc nhau ca c th dn n s khc nhau r rt ca lng cht tch ly; iu ny ph thuc vo tng lng lipid vi iu kin tui hoc gii tnh ca sinh vt .

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S phng i sinh hc (biomagnification) trong qu trnh tch ly v chuyn ha sinh hc ca c cht, c t qua chui thc phm. Nu sinh vt sng tng y n phi mt lng nh c cht, c t th ng vt n tht s n gp 100 ln so vi sinh vt tng y. Bng cch , con ngi s v tnh n phi mt lng rt ln cht c.!44

II.2. S hp thu, phn phi v o thi cc cht c trong c th1. C ch cht c

xm nhp vo c th

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II.2. S hp thu, phn phi v o thi cc cht c trong c th

1. C ch cht c xm nhp vo c th ! Khuch tn th ng S thm lc Vn chuyn ch ng (tch cc) Ni thm bo

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1. C ch cht c xm nhp vo c th Cu trc t bo

Mi t bo c mng, bo

tng, cc bo quan v nhn.

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1. C ch cht c xm nhp vo c th c Chc nng ch yu ca t boTo ra hng ro bo v, to hnh, n nh cu trc

c trong v ngoi. Tip nhn, x l v truyn tin. Tip nhn, tiu ha cht, tng hp cht mi, sinh nng

lng. D tr cht v nng lng. Sinh sn thay c i mi, pht trin c th, hi

phc c th, duy tr ni ging. Sinh in sinh hc: in no, in tim, in thn kinh, in d dy

S trao i thng tin v vt cht qua mng t bo thng qua hnh thc vn chuyn khuch tn, vn chuyn tch cc, thm lc v ni thm bo.

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1. C ch cht c xm nhp vo c thc Cu trc mng t bo

Mng t bo l mng bn thm, c tnh n hi, dy 7-10 nm, thnh phn ch yu l protein v lipid, mt phn nh l carbohydrat.

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1. C ch cht c xm nhp vo c th Cc hnh thc chnh vn chuyn vt cht qua

mng t bo

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1. C ch cht c xm nhp vo c th Vn chuyn th ng xy ra ph thuc vo s

chnh lch nng cht v in th hai bn mng t bo, khng cn cung cp ATP. !!!!!!

Vn chuyn ch ng (tch cc) cn c cung cp ATP hot ng.

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C ch cht c xm nhp vo c thc Khuch tn th ng1. Qua lp lipid kp (phospholipid):

Vt cht c kch thc nh Khng tch in Khng phn cc Nhng cht ha tan trong lipid

2. Qua protein mang tnh chn lc: ng, acid amin, cc ion Na+, K+, Ca2+, Mg2+, P3+, Cl1-

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C ch cht c xm nhp vo c thc Khuch tn th ng

1. Khuch tn n thun qua lp lipid kp Cc cht c bn cht l lipid, tan trong lipid O2; N2;

CO2; cc vitamin A, D, E, K, ru; cn... Tc khuch tn t l thun vi ha tan trong m.- c im: vn chuyn vt cht thun chiu bc thang in ha ly nng lng t chuyn ng nhit, khng cn cung cp ATP .

Ring, i vi nc qua mng rt nhanh do kch thc phn t nh v ng nng ln, hoc cc phn t khng tan trong m nhng c kch thc rt nh (ur). Vy, trng hp ny th c tc khuch tn t l nghch vi kch thc phn t.

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2. Khuch tn n thun qua cc knh protein C tnh thm chn lc cao: ph thuc vo c im hnh

dng, ng knh v in tch mt trong ca knh. Cng ng- m ca knh protein theo in th: V d: Cng hot ha ca knh Na+: Khi mt trong mng

mt in tch m th cng hot ha pha ngoi mng m ra, Na+ i qua knh vo trong t bo. Cng ca knh K+ cng m khi mt trong mng tr thnh in tch dng.

Cng ng m do cht kt ni (ligand): Khi c cht kt ni gn vi protein knh lm thay i hnh dng v lm ng hoc m cng.

V d: Acetylcholin gn vo protein knh, Na+ lm cng ca knh m ra, cho php cc ion Na+ i vo tham gia vo c ch xut hin in th hot ng, dn truyn xung ng thn kinh.

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C ch cht c xm nhp vo c thc Khuch tn th ng3. Khuch tn c thun ha nh protein mang L hnh thc vn chuyn ca cc ng n nh

glucose, fructose, mannose, galactose, xylose, arabinose v phn ln cc acid amin.

Tc khuch tn tng dn n mc ti a (Vmax) th dng li d nng cht khuch tn vn tip tc tng.

Nguyn nhn: s lng cc v tr trn phn t protein mang c hn, c thi gian protein mang gn, thay i hnh dng.

!55

C ch cht c xm nhp vo c thc Khuch tn th ng Khuch tn c thun ha nh protein mang

!56


nh hng bi tnh thm ca mng i vi cht khuch tn.

nh hng bi s chnh lch nng hai bn mng.

nh hng bi s chnh lch p sut qua mng.

Khi c chnh lch in th gia hai bn mng th cc ion, do tch in, s khuch tn qua mng mc d khng c s chnh lch nng ca chng hai bn mng.

4. Cc yu t nh hng ti tc

khuch tn th ng

!57

c Khuch tn th ng c cht qua mng t bo

! Phn ln cc cht c i qua mng t bo bng

con ng khuch tn n gin v th ng. T l i qua c lin quan trc tip vi gradient nng hai bn mng v tnh a bo ca phn t c.

Nhiu cht c ion ha c. Cc dng ion ha thng khng c kh nng i qua mng t bo do ha tan ca chng trong lipid rt thp, trong khi dng khng b ion ha li ha tan c trong cht bo, do t l hp th ph thuc vo ha tan ca chng trong cht bo.

!58


ion ha ca acid v base hu c yu ph thuc vo pH ca mi trng. V th, s khuch tn ca acid th rt d dng trong mi trng acid, trong khi mt base li khuch tn nh nhng trong mi trng kim.

S khuch tn th ng thng c xu hng thit lp nn mt cn bng gia cc nng tn ti hai pha mng sinh hc.

Thi gian t n mt cn bng gia mt c th v mi trng quanh n, ngoi a bo, cn ph thuc vo nng vt cht trong mi trng, b mt trao i v khi lng ca c th, trong quan trng l lng m ca c th ny.

!59


D dy

!60


Rut

!61

II.2. S hp thu, phn phi v o thi cc cht c 1. C ch cht c xm nhp vo c th (tip)

c S thm lc qua mng t bo Cc mng ca cc mao qun v ca cc cun tiu

cu thng c cc l tng i rng (khong 70 nm) nn cc phn t c kch thc b hn albumin (M=60.000 Da) u c th i qua c.

Nh lc thy tnh v/hoc lc thm thu m dng nc i qua cc l ny s gp phn vo vic vn chuyn cc cht c.

Tuy nhin cc l t bo a phn l kh nh (khong 4 nm) nn ch c cc sn phm ha hc c khi lng phn t cc i l 100-200 Da, mi i qua c.

!62


1. C ch cht c xm nhp vo c th c Vn chuyn tch cc l hnh thc vn chuyn

ca ion Na+, K+, Ca2+, Fe2+, H+, Cl-, I-, urat, mt s ng n v phn ln acid amin.

Ngc chiu bc thang in ha. Cn phi c cht mang v cn cung cp nng

lng t bn ngoi.

!63

1. C ch cht c xm nhp vo c th c Vn chuyn tch cc

Uniport: ch vn chuyn mt cht duy nht Symport: vn chuyn c hai cht cng mt lc

theo cng mt chiu. Antiport: vn chuyn hai cht cng mt lc nhng

theo hai chiu i ngc nhau (bm Na+ - K+ -ATPase)

!64

S vn chuyn tch cc thng bao gm c ch to ra mt phc gia phn t v cht mang cao phn t ti mt pha ca mng. Lc ny, phc c th khuch tn qua pha bn kia mng v ti y phn t s c gii phng. Sau , cht mang li quay tr v v tr ban u v qu trnh li tip tc.

Tuy nhin, kh nng ca cht mang thng c gii hn. Khi cht mang b bo ha th t l vn chuyn khng cn ph thuc vo nng ca phn t.


!65


C ch bm Na+, K+ v ATPase ca t bo: Bm Na+,K+, ATPase c vai tr a 3 ion Na+ vo

trong, 2 ion K+ ra ngoi, ko nc ra theo. Khi Protein v cc hp cht hu c c kch thc

phn t ln, tch in m, khng th thm ra ngoi mt cch th ng (trng thi ngh ca c ch th ng), s hp dn cc ion dng v gy ra mt lc thm thu ht nc t bn ngoi vo bn trong lm t bo phng ln v c th v. Do vy, c ch bm Na+ -K+ - ATPase, s c hot ha khi th tch t bo tng hn bnh thng.

!66

1. C ch cht c xm nhp vo c th c Vn chuyn tch cc Hin tng km hm cnh tranh cng c th xy

ra gia nhng phn t c cc c tnh tng t nhau.

!67


Trong vn chuyn tch cc, mt cht mang c th m bo cho cc phn t qua mng ngc vi gradient nng , hoc nu phn t dng ion ha th cht mang cng s m bo cho chng qua mng ngc vi gradient in ha.

Tt nhin, s vn chuyn tch cc phi tiu tn mt nng lng ca trao i cht, do qu trnh s b c ch bi nhng cht c vn c nh hng ti s trao i cht ca t bo.

!68


1. C ch cht c xm nhp vo c th c Ni thm bo Cc tiu phn dng rn c th b hp thu bi thc

bo. Cc tiu phn dng lng b hp thu bi ung bo. C ch ny c gi l nhp bo.

H thng vn chuyn c bit ny rt quan trng i vi cc ti phi cng nh i vi h thng li ni m khi bi tit cc cht c c trong mu.

!69

1. C ch cht c xm nhp vo c thc Ni thm bo i vi cc phn t ln (rn hoc lng) khng lt

qua l mng, t bo s dng hnh thc xut hay nhp bo chuyn ti ra hoc vo t bo.

!70


2. Qu trnh xm nhp ca c cht vo c th sinh vt

c cht xm nhp vo c th sinh vt t rt nhiu con ng khc nhau v ty thuc vo tng nhm loi sinh vt.

Thc vt ng vtCon ngi!71


2. Qu trnh xm nhp ca c cht vo c th sinh vt c i vi thc vt c cht c th xm nhp bng cch th ng

hay ch ng. c cht xm nhp vo c th thc vt qua qu

trnh ly cc cht dinh dng, mui khong t b r, t c quan hp thu, sinh sn, d tr nh l hoa qu, mt s cht c th thm thu trc tip qua mng t bo khi tip xc.

!72


2. Qu trnh xm nhp ca c cht vo c th sinh vt c i vi ng vt c cht xm nhp vo c th ng vt: Qua ng h hp Thm qua da Qua ng tun hon Qua ng tiu ha Qua cc c quan d b tn thng, nhy cm vi c cht.

Chuyn ha (Metabolism)

o thi (Elimination)

Hp th (Absorption)

Phn phi (Distribution)

!73

II.2. S hp thu, phn phi v o thi cc cht c trong c thc i vi con ngi

!74


Cht c qua ming (s n vo bng)

Cht c qua phi (s ht vo)

Thm qua da

ng ng tiu ha Mt

Gan

H thng tun hon ca mu/ bch huyt

Cc con ng khc (trc trng,

m o, ngoi rut)

Bi tit (th ra khng kh)

Bi tit (tuyn m hi)

Bi tit (phn)

Lin kt Protein Trao i chtPhn phi ( dng t do,

lin kt, cht chuyn ha)

C quan cm nhn mng t bo

Tch t (xng, m m)

Thn

Bng quang

Bi tit (nc tiu)!75


1 Qu trnh hp thu Bn con ng chnh: tiu ha, h hp, thn kinh

v thm qua da. a. ng tiu ha a phn cc cht c i vo ng tiu ha cng

vi nc v thc n hoc i vo mt cch c lp qua ming, d dy, rut non, gan (c gii c mt phn), qua ng tun hon, n cc ph tng v gy nhim c.

Tuy nhin, khng phi tt c cc c cht u i qua c m ch c nhng phn t c ng knh c 0,1 mm, i qua cc k h ca t bo cht rut non, lt vo t bo cht.

!76

D dy Rut non

gan


Hp thu qua ng tiu ha: Trong t bo cht, chng hy

hoi t bo cht rut non, sau i vo mu ph v bch cu, lm gim sc khng ca con ngi. Mt s loi cht c tr li trong m m hay trong gan, xng

Khi c cht tn cng vo rut hay d dy, tnh hp ph ca c cht b thay i.

"77


Trong d dy Cht c l cc acid yu,

chng thng dng khng ion ha, ha tan c trong cht bo nn c th khuch tn c.

Cht c l cc base yu, chng b ion ha rt mnh do b hp th khng d dng.

Qua mu, cc acid yu thng di dng ion ha nn d b vn chuyn i, con base yu li thng di dng khng ion ha nn c khuynh hng khuch tn li d dy.

Trong rut Cht c l cc acid yu, ch yu dng ion ha nn b hp thu kh khn, nhng mt khi qua c vo mu th chng tr thnh dng ion ha do s khng c xu hng quay tr li.

Cht c l cc base yu, th d dng b hp th hn v y chng tn ti di dng khng ion ha.

Nhng cht phn cc km thng l nhng cht tan trong m, thng qua mng lipid v nhng cht tit ra trong qu trnh ion ha, ph thuc vo h s phn ly v pH dung dch."78


Qu trnh hp thu b. ng h hp y l con ng xm nhp quan trng nht v

lun xy ra do con ngi phi th ht. Phi ngi c din tch trao i kh l 90 m2, trong 70 m2 l ca ph nang. Ph nang l vng hp thu chnh ca ng h hp bi v n c b mt hp thu rt ln, c lu lng mu cao v c s gn gi gia mu v khng kh ph nang.

"79


Qu trnh hp thu c. Thm qua da Da c vai tr bo v chng cc yu t ha hc, l

hc v sinh hc. Da c tnh khng thm cao, to nn mt hng ro ngn cch gia c th v mi trng. Tuy nhin mt s sn phm ha hc c th hp thu qua da, i qua lp biu b v chn b, i vo h tun hon v gy nhim c cho c th.

"80


Qu trnh hp thu d. Tc ng qua h thn

kinh Gy chong vng mc

nh. T lit mc nng. Gim tr nh, c th tr nn n n.

Kch pht v c th tr nn hung bo.

C th tc ng di truyn v s sai lch, lon tr nh.

"81


2 Phn b Phn b qua hng

ro mu no, hng ro ny c nh v thnh mao mch.

Cc t bo ca ni m m a o m c h thng ni kt cht ch vi nhau, do c tc dng ngn cn s i qua ca cc cht c.

Cu to mch mu"82


Phn b Trong cc t bo ny li thiu cc khng bo nn

cng lm gim kh nng vn chuyn c cht. Nng protein ca cc cht lng cc khe

trong no thng rt thp. V vy, s lin kt vi cc protein khng th l mt c ch vn chuyn ca cht c t mu vo no.

Cc cht c vo trong no ph thuc vo ha tan ca chng trong cht bo.

"83


Phn b Hng ro mu nhau l vt cn tr ngi cho s

vn chuyn cc cht c v do c mt tc dng bo v no cho cc bo thai.

Cc hng ro khc c mt, tinh hon. Cc hng cu cng c vai tr trong s phn b s xm nhp cc dn xut v c thy ngn nhng li khng cn tr cc dn xut alkyl ca thy ngn.

"84


3 C nh v thu gi cht c Sau khi vo c th cc cht c lu thng trong

mu, bch huyt, n cc t chc v ph tng. Vic c nh mt sn phm ha hc vo mt t chc no thng lm cho nng cc b t chc ny cao hn.

Hai kiu lin kt vi cht c: Nhng cht c tc dng c mnh, lin kt bng ng ha tr khng thun nghch.

Nhng cht lin quan n liu lng, lin kt phi ng ha tr thun nghch. Lin kt ny c vai tr trong s phn b v lu gi nhiu c quan v m. "85


C nh v thu gi cht c trong protein dch tng

Cc protein dch tng c th c nh cc hp phn sinh l bnh thng cng nh cc hp phn ngoi sinh.

Phn ln cc hp phn ngoi sinh c lin kt vi albumin, do khng c vn chuyn trc tip vo trong khong khng gian ngoi mch.

Tuy nhin, s lin kt ny thng l thun nghch nn phn t cht c c kh nng t phn ly khi protein dn n lm tng lng cht c t do, chng c th i qua ni m ca mao mch.

"86


C nh v thu gi cht c trong gan v thn Gan v thn c kh nng c nh cc phn t ha

hc, c chc nng trao i cht v chc nng bi xut ca chng.

Phn ln cc ion v c (Cadimi, asen, ch, ng) ng li gan bi cc protein c kh nng c nh c bit (metalothionein) hoc chuyn giao kim loi t gan ti thn v thi ra theo ng tiu ha.

"87


C nh v thu gi cht c trong m m Cc m m l ni tch gi mnh cc hp cht ha

tan c trong cht bo (m trung tnh, cc acid bo) nh cc dung mi, cc ha cht tr su chlor hu c. S kt hp cc cht c nh DDT vi cc acid bo, c kh nng gi sn phm ny trong cc t bo giu lipid gan, thn v thn kinh trung ng.

"88


C nh v thu gi cht c trong m m v xng

Xng l vng chnh gi cht c nh flo, ch v stronxi (Sr). Cc cht c c mt trong cht lng gia cc khe d b c nh do phn ng trao i nhanh vi cc tinh th hydroxyapatit ca xng v do c s ging nhau v in tch v kch thc nn ion F c th thay th d dng OH-, Ca+ c th b thay th bi ch hoc Sr.

"89


4 Thi cht c Cc cht c sau khi hp thu v phn b trong c

th, th nhanh hay chm u b bi xut ra, hoc di dng khng i hoc di dng cc cht trao i ca chng hoc di dng cc hp cht lin hp.

Nc tiu l con ng bi xut chnh, nhng i vi mt s phn t th gan v phi li c vai tr quan trng.

"90


Thi cht c qua thn Cc cht c, cc sn phm chuyn ha c thm

lc qua tiu cu thn, khuch tn qua ng thn v bi tit qua ng thn.

Cc mao qun ca tiu cu thng c l rng (70 nm) nn phn ln cc cht c u c th i qua, tr nhng cht c c kch thc ln (M>60.000 Da) hoc c lin kt cht ch vi cc protein dch tng.

Mt cht c cng c th c bi xut vo trong nc tiu bng khuch tn th ng qua cc ng. Nc tiu bnh thng c tnh acid nn qu trnh ny c lin quan ti s bi xut cc base hu c. "91


Thi cht c qua gan v mt Gan cng l mt c quan quan trng trong vic

bi xut cc cht c, c bit l cc hp cht c cc mnh (anion hoc cation), cc dn xut c lin kt vi protein bo tng v cc hp cht c khi lng phn t cao hn 300 Da.

"92


Thi cht c qua phi Khi cc sn phm dng kh hoc cc dng cht

lng bay hi nhit c th u c bi xut ch yu qua phi. Chng c khuch tn n gin qua mng t bo hoc theo kh trong khi th ra ngoi. Tuy nhin, t l v thi gian o thi ca tng cht khc nhau.

V d: Chloroform thng bi xut rt chm do n c gi trong m m v do th tch thng kh phi b hn ch.

"93


Thi cht c qua cc ng khc Bi xut qua ng tiu ha bng khuch tn: Cht c theo ming, theo thc n, vo d dy trong c th ri phn b trong mu tun hon ti gan. , cht c chu tc dng ca mt v cc men, ri qua rut v b thi theo phn.

Bi xut qua nc bt, tuyn sa v m hi: y l con ng bi xut ti thiu ca mt s c cht kim loi v cht hu c. S bi xut c tin hnh bng khuch tn v thng gii hn dng c khng ion ha nhng ha tan c trong cht bo.

"94

II.3. Chuyn ha sinh hc cc c t - s cn bng gia cht c hi v cht kh c

1. Bn cht phc tp ca s chuyn ha sinh hc cc c t

! Mt cht c c th b chuyn ha theo nhiu phn

ng khc nhau, to thnh nhng hp cht trao i v nhng hp cht lin kt khc nhau.

Mt cht c c bao nhiu nhn t nh hng (sinh l, mi trng, ha hc) th c by nhiu kiu chuyn ha sinh hc v by nhiu sn phm chuyn ha khc nhau.

"95


S chuyn ha sinh hc

"96


1. Bn cht phc tp ca s chuyn ha sinh hc cc c t !

Mt cht c trong mt c quan sinh hc ny th n c th c chuyn ha thnh mt cht trao i bn. Nhng nu c chuyn sang mt c quan khc th n c chuyn ha thnh mt cht trao i cui cng.

Cc phn ng trao i cht thng phn ng theo chui, do vy c nh hng n tc dng c ca cht.

"97


2. S cn bng gia cht c hi v cht kh c

Chuyn ha sinh hc ca cc c cht l s bin i ca cc cht ha hc do c s phn chia hay b sung thm cu trc ca n, cc enzyme chuyn ha cht c c th lm thay i c tnh ca ha cht v sn phm cht chuyn ha c phn phi v tch t trong c th.

Bn cnh s chuyn ha sinh hc mang li nhiu li ch trong vic bo v c th khi ha cht t mc cao bn trong nhiu m c, s tch ly lu di c kh nng chuyn ha sinh hc cht c hoc gia tng c tnh ca ha cht."98


2. S cn bng gia cht c hi v cht kh c Trong , mt vi sn phm cht chuyn ha l

cht gy t bin gen v/hoc cht gy ung th. Do , s chuyn ha c cht c th to ra 3

dng cht chuyn ha/trao i:

1. C th l cht chuyn ha khng c.

2. C th l cht c nhng sau c th t kh c.

3. C th l cht c v khng c s kh c lm gim c tnh trc khi t bo hay m c b tn thng.

"99

Cn bng gia cht c hi v cht kh c Gan l b phn chnh c chc nng chuyn ha

sinh hc cc ha cht. N l b phn u tin phi nhim cc ha cht hp th t rut v c xem nh l ci cng li ra ca cc cht bi tit.

Mt s yu t c th bin i kh nng chuyn ha cht c khi con ngi v tnh b phi nhim gm ch n kin hay dinh dng thc phm, tui, gii tnh, tnh trng hormone v gen di truyn, kh nng hp thu, tch ly hay o thi v kh nng c ch enzyme chuyn ha sinh hc

"100

Gii c (detoxication) hoc kh c (detoxification) Phi c th kh c bng cch th kh (kh gy m c loi ra khi c th qua phi).

Da c th kh c bng cch thm cht c qua da (c cht tan trong nc khng thm qua da tt, nhng cht c tan trong du c th thm qua d dng).

H thng tiu ha c th kh c bng cch bi tit c cht thc phm, bng cch nn ma hoc tiu chy.

Thn c th kh c bng cch lc v bi tit cht c trong mu vo nc tiu.

Gan c th kh c bng cch thay i bn cht ha hc ca nhiu c cht.

"101

S hp thu, chuyn ha v bi tit

- a: v tr hp thu chnh

- e: v tr bi tit - f: v tr lc - m: v tr chuyn ha

chnh - p: sn phm

chuyn ha - s: v tr cht bi tit - x: cht c sau

chuyn ha sinh hc

"102

Vai tr chuyn ha sinh hc c bi tit trong nc tiu

"103

II.3. Chuyn ha sinh hc cc c t - s cn bng gia cht c hi v cht kh c Cn bng phn ng v cht bi tit trong qu trnh

chuyn ha sinh hc

"104

V d: Chuyn ha sinh hc ca Benzen

Pha I Pha II

Oxidation Sulfate conjugation

Reduction Glucuronide conjugation

Hydrolysis Glutathione conjugation

Acetylation Amino acid conjugation"105

Phn ng Pha I Cht c tri qua qu trnh chuyn ha sinh hc

pha I chuyn ha thnh cht trao i. Sau , cht ny c th c o thi ra ngoi c th m khng tip tc chuyn ha hoc n c th l cht trao i trung gian tip tc cho qu trnh chuyn ha pha 2.

Cht chuyn ha trung gian pha I c th tng c tnh hn so vi cht c ban u.

Phn ng pha I gm ba phn ng chnh: phn ng oxy ha, phn ng kh v phn ng thy phn (gi chung l phn ng thoi phn).

"107

Phn ng pha II Cht chuyn ha tri qua phn ng chuyn ha

pha I by gi l cht chuyn ha trung gian mi, bao gm nhm phn ng ha hc: hydroxyl (-OH), amino (-NH2) v carboxyl (-COOH).

Nhiu cht trao i trung gian khng c tnh thm cho php o thi ra ngoi c th. Nhng cht chuyn ha ny phi tri qua phn ng trong qu trnh chuyn ha sinh hc ln na pha II.

"108

Pha II Phn ng pha II l phn ng lin hp, ngha l cht

chuyn ha pha I s phn ng kt hp vi mt phn t hin din trong c th to ra cht chuyn ha lin hp, c kh nng ha tan trong nc hn cht chuyn ha pha I hoc cht c ban u. Thng thng, cht chuyn ha pha II c tnh thm cao v c th o thi ra ngoi c th. Cc phn ng pha II gm: Glucuronide conjugation Phn ng quan trng nht Sulfate conjugation Phn ng quan trng Acetylation Amino acid conjugation Glutathione conjugation Methylation"109


3. Phn ng thoi phn Phn ng thoi phn bao gm cc phn ng: Phn ng oxi ha Phn ng kh Phn ng thy phn

"111


3. Phn ng thoi phn Phn ng oxi ha Oxygenase l enzyme xc tc trong qu trnh lin

kt oxy ca khng kh, enzyme ny s ct lin kt gia hai nguyn t oxy v st nhp mt hoc hai nguyn t oxy vo c cht ca chng. Enzyme monooxygenase Enzyme dioxygenase Nu phn ng khng c s xc tc bi mt

oxydase, hai nguyn t oxy s khng b ct v khng lin kt vi c cht m to ra nhng hp cht nh H2O2.

"112


a. Enzyme monooxygenase S oxy ha c cht ch c th tin hnh c khi

enzyme monooxygenase lin kt mt nguyn t vo c cht nh mt ngun electron t NADH2 hoc t NADPH2, phn t oxy cn li b loi b di dng phn t nc

RH2 + O-O ROH

H+ H2O

NADPH2 NADP+

"113


b. Enzyme dioxygenase: Enzyme dioxygenase lin kt c hai nguyn t

oxy vo c cht nhng hai v tr khc nhau. Dioxygenase thng xc tc s oxy ha cc hp cht thm (m vng cht thm) v khng cn s tr gip ca ngun electron ph.

RH2 + O-O ROH

H

"114

Mt s phn ng oxy ha

Alcohol dahydrogenation Aldehyde dehydrogenation Alkyl/acyclic hydroxylation Aromatic hydroxylation Deamination Desulfuration

N-hydroxylation N-oxidation S-oxidation O-dealkylation S-dealkylation Sulphoxidation

"115

ALCOHOL DEHYDROGENATION

"116

DEAMINATION

"117

DESULFURATION

"118

N-DEALKYLATION

N,N-dimethyl-p-nitrophenylcarbamate

"119

N-OXIDATION

"120

S-OXIDATION

sulfide sulfoxide sulfone

"121

O-DEALKYLATION

p-Nitrosanisole

"122

S-DEALKYLATION

"123


3. Phn ng thoi phn Phn ng kh Phn ng kh bi cc enzyme ca vi th thn

Kh cc dn xut nitro: C6H5-NO2 C6H5-N=O C6H5NHOH C6H5-NH2 Nitrobenzen Nitrosobenzen Phenylhydroxylamin Anilin

Kh cc dn xut azo: C6H5-N=N-C6H5 C6H5-NH-NH-C6H5 C6H5-NH2 Azobenzen Hydrazobenzen Anilin Phn ng kh bi cc enzyme phi vi th thn (phn

ng ngc ca enzyme alcoldehydrogenase)."124

Mt s phn ng kh Azo reduction Dehalogenation Disulfide reduction Nitro reduction N-oxide reduction Sulfoxide reduction

"125

AZO REDUCTION

"126

DEHALOGENATION

"127

NITRO REDUCTION

"128


3. Phn ng thoi phn Phn ng thy phn Nhng cht c c lin kt ester d dng b thy

phn, mt s enzyme esterase nh v trong phn tan ca t bo thng xc tc phn ng thy phn: Arylesterase thy phn cc ester thm. Cacboxylesterase thy phn cc ester dy bo. Cholinesterase thy phn cc ester c gc l

mt ru. Acetylesterase thy phn cc ester ca axit

acetic. "129

Procaine d dng b thy phn bi esterase trong plasma.

"130

II.3. Chuyn ha sinh hc cc c t - s cn bng gia cht c hi v cht kh c4. Phn ng lin hp (conjugation reaction) !Phn ng lin hp thng xy ra cc phn ng: Phn ng lin hp vi acid glucuronic. Phn ng lin hp vi acid sulfuric, sulfate. Phn ng lin hp vi axid acetic. Phn ng lin hp vi glutathion.

"131


4. Phn ng lin hp Phn ng lin hp vi acid glucuronic hot ha Di tc dng ca enzyme

uridindiphosphatglucuronyltransferase nh v vi th gan, nhiu cht c lin hp c vi acid glucuronic hot ha (acid uridindiphosphatglucuronic - UDPGA) to ra cc dn xut glucuronid, nh: Alcol v phenol: to ra dn xut eter glucuronic. Acid carboxylic: to ra dn xut ester glucuronic. Cc acid amin: to ra dn xut N-glucuronid. Vi hp cht c S: to ra dn xut S-glucuronid.

Thc phmUDPGA + X (cht c) X-glucuronid+ UDP "132

Phn ng lin hp vi acid glucuronic hot ha Phn ng lin hp ca Aniline

Phn ng lin hp vi glucuronic l mt phn ng quan trng v thng xy ra phn ng pha II. Phn ng ny thng c kh nng lm gim c tnh ca cht c, mc d c mt vi trng hp ngoi l ng k, v d nh sn phm cui cng c th l nhng khi u. Sn phm lin hp vi glucuronic c tnh thm cao v c th bi tit ra bi thn hoc mt, ph thuc vo kch thc ca sn phm chuyn ha cui cng.

"133


4. Phn ng lin hp Phn ng lin hp vi acid sulfuric Cc phenol, alcol mch thng phn ng ester ha

vi cc acid sulfuric v thi ra di dng ester sulfuric. Phn ng ny thng c xc tc bi enzyme

sulfotransferase nh v trong bo tng ca gan, thn v rut.

enzymeC6H5OH + H2SO4 SO4 + H2O

H

C6H5

"134

Phn ng lin hp vi acid sulfuric, sulfate

Phn ng lin hp vi acid sulfuric, sulfate l phn ng quan trng khc pha II, to ra nhiu sn phm chuyn ha c tnh c.

Thng thng, sn phm lin hp gim c tnh so vi cht c ban u.

Ging nh sn phm lin hp vi acid glucuronic , n thng c o thi qua mt, sn phm lin hp vi sulfate phn cc cao nn n cng d dng o thi qua nc tiu.

"135


4. Phn ng lin hp Phn ng lin hp vi acid acetic Nhng cht c cha amin bc nht nh histamin,

hydrazin, sulfonamid c th lin hp vi acid acetic.

H

HN SO2NH2 + CH3COOH N

H

CH3-C=OSO2NH2

Sulfonamid Acid Acetic

"136


4. Phn ng lin hp Phn ng lin hp vi acid glutathion (glutathione) Cc hp cht (cc hp cht khng no mch thng, cc

phn t c nhm nitro) lin hp vi glutation (GSH), xc tc bi enzyme glutation-S-transferase. Sau b ct bi mt enzyme v c acetyl ha to ra nhng dn xut N-acetylcystein ca cht c, d dng c bi tit hn.

+ GSH

GSH-S-Transferase

ClCl Cl

NO2 NO2

SG

"137

Phn ng lin hp vi acid glutation (glutathione)

Trong qu trnh chuyn ha sinh hc, cc cht c thng to ra hp cht electrophil, l cht gy tng tc vi cc hp phn t bo gy hoi t t bo hoc gy sinh khi u.

Glutation c chc nng phn ng vi cc cht trao i electrophil, ngn nga tc dng c ca chng n t bo.

Phn ng lin kt vi glutation l con ng quan trng nht, v phn ng ny c coi l mt c ch bo v.

Tuy nhin, khi sn phm c tng ln hoc enzyme ca vi th c cm ng v hot ha ln th lng glutation s gim.

"138


5. Phn ng hot ha Nhiu hp cht ha hc c th c hot ha thnh

cc cht c kh nng phn ng v c kh nng gy c cho c th. Phn ng hot ha bao gm cc phn ng:

Phn ng to epoxyd. Phn ng N-hydroxyl ha. Phn ng to cc gc t do v cc ion superoxyd. Hot ha trong ng tiu ha.

"139


Mt s hp cht c th c hot ha v gy c c bn

Hp cht ban u (1)

Cht chuyn ha c c tnh (2)

C ch gy c (3)

c tnh (4)

Acetaminophen Dn xut N-hydroxy

Lin kt ng ha tr

Hoi t gan

2-Acetaminofluoren (AAF)

N-Acetoxy-AAF Lin kt ng ha tr

Cc ung th

Aflatoxin B Aflatoxin-2,3-epoxyd

Lin kt ng ha tr

Ung th gan

"140


Mt s hp cht c th c hot ha v gy c c bn

(1) (2) (3) (4)

Allyl format Acrolein Lin kt ng ha tr

Hoi t gan

Amygdalin Mandelonitril To ra cianua Gim oxy mu

Benzen Benzen epoxyd Lin kt ng ha tr

Tn thng ty xng

Brombenzen Brombenzen epoxyd Lin kt ng ha tr

Hoi t gan, thn

"141

(1) (2) (3) (4)Cacbon

tetracloruaGc t do

(triclometan)Lin kt ng

ha trHoi t v ung th

gan

Chloroform Phosgen Lin kt ng ha tr

Hoi t gan v thn

Cycasin Metylazoxymetanol

Alkyl ha Cc ung th, hoi t gan

Hydrocacbon a vng

Epoxyd Lin kt ng ha tr

Cc ung th, gy c t bo

Metanol Formaldehyd Phc hp c tnh chung v vng mc

"142

(1) (2) (3) (4)

Methoxyfluran Florua v c c ch enzyme

Tn thng thn

Nitrat Nitrit Oxy ha hemoglobin

Methemoglobin-mu

Nitrit v cc amin bc 2, bc 3

Notrosamin Alkyl ha Cc ung th gan v phi

Parathion Paraoxon Lin kt ng ha tr

T lit thn kinh c

Uretan N-Hydroxyuretan Alkyl ha Cc ung th, c t bo

"143


5. Phn ng hot ha Phn ng to epoxyd Nhiu hp cht vng c th c chuyn ha thnh

epoxyd bi cc monooxygenase ca vi th. !!!!!!

Brombenzen Brombenzen epoxyd

Vi th

NADPH2+O2 H

Br Br

H O

"144

II.3. Chuyn ha sinh hc cc c t - s cn bng gia cht c hi v cht kh c Phn ng to epoxyd Sau khi hnh thnh Bromobenzen epoxyd, phn ng

lin kt vi glutation lm gim kh nng gy c. Ch sau khi lng glutation gan b gim mnh th bromobenzen epoxyd mi lin kt vi cao phn t v gy hoi t gan.

H

Br

OHH

Br

OH

OHGSH transferase

Lin kt bng ng ha tr vi cc cao phn t

3,4-ihyro-3-hydroxy-4,S-glutathionyl-brombenzen

"145


5. Phn ng hot ha Phn ng N- hydroxyl ha Mt s sn phm N-hydroxyl ha bi cc enzyme ca v

th t cc cht acetaminophen, 2-acetylamino-fluoren (2-AAF), uretan v mt s cht mu azoic. Do cc sn phm N-hydroxyl ha c th lin kt ng ha tr vi cao phn t, chng u l nhng cht gy ung th hoc gy hoi t m.

Sn phm N-hydroxyl ha ca cc amin d vng thng gy chng tiu mu hoc chng to methemoglobin-mu.

Nu cc hp cht N-hydroxyl lin kt vi acid glucuronic, d dng bi xut. Nu chng lin kt vi acid sulfuric hoc acid acetic, c tc dng gy t bin v gy ung th."146


5. Phn ng hot ha Phn ng to cc gc t do v ion superoxyd Mt s cht c halogen c th chuyn ha thnh cc gc

t do. Hot ha trong ng tiu ha Trong mi trng acid ca dch d dy, cc nitrit v mt

s amin c th to ra cc nitrosamin (gy ung th) v cc nitrat (trong iu kin khc, nitrat b chuyn i thnh nitrit bi h vi sinh vt ng tiu ha, to ra methemoglobin mu).

Cht ngt nhn to cyclamat (ng ha hc thng dng) b chuyn ha thnh cyclohexylamin bi cc vi khun ng rut gy teo tinh hon.

"147

II.4. Tc dng c ln c th

Tc dng c l kt qu tng tc ha sinh gia phn t cht c (v/hoc cht trao i ca n) vi cc cu trc ca c th. !

Tc dng c tng hay gim ph thuc vo bn cht, c quan ch v c ch tc dng ca c cht, c t.

"148

II.4. Tc dng c ln c th Qu trnh tc dng c ca cc c cht

Hp th cht c

Pha ngTrao i cht, chuyn ha Tch tr Bi tit

Phn ng ha sinh Lin kt cc c quan nhy cm (receptors)nh hng ha sinh

c ch enzyme; Thm c qua mng t bo; Thay i cu trc protein, m m v chuyn ha carbohydrate; Hn ch h hp

Tc dng c

Thay i nhit , tc nhp p ca tim, nhp th, p sut mu v h thng thn kinh trung ng"149


1. Tnh a dng ca cc tc dng c Tc dng c cc b v tc dng c h thng Tc dng c cc b l tc dng ca mt s cht c

c th gy tn thng trc tip ln b mt tip xc ca c th (da, ng tiu ha, ng h hp), ph hy cc t bo sng. V d: acid sulfuric, xt, chloroform

Tc dng c h thng l kt qu tc dng c ca cc cht c sau khi cht c c hp thu v i vo mt hoc mt s c quan, b phn khc nhau ca c th. V d: Bromobenzen, Nitrit, Nitrat

"150


1. Tnh a dng ca cc tc dng c Tc dng c tc thi v tc dng c chm Tc dng c tc thi l tc dng c ngay tc khc

sau ch mt ln tip xc. V d: Cyanua, Tc dng c chm l kt qu tc dng c th hin

sau 10-20 nm sau ln tip xc ban u. V d: Nhng hp cht gy ung th nh: Aflatoxin, Cyacin, Nitrit

"151

II.4. Tc dng c ln c th1. Tnh a dng ca cc tc dng c Tc dng c hnh thi v tc dng c chc nng Tc dng c hnh thi l tc dng c dn n s

thay i hnh thi ca m, nh s to m mi hoc s hoi t m. V d: Cacbon tetraclorua, Chloroform,

Tc dng c chc nng (tc dng c ha sinh) l tc dng thay i thun nghch cc chc nng ca mt c quan (khng lm thay i hnh thi), nh to s c ch mt s enzyme khi c s hin din ca cc cht c. V d: enzyme cholinesterase b kim hm sau khi tip xc vi cc cht dit cn trng.

"152


1. Tnh a dng ca cc tc dng c Phn ng d ng v phn ng c ng Phn ng d ng l phn ng p li tin quyt trc

mt phn t c. V d: d ng vi thy sn, vi albumin,

Phn ng c ng l mt s nhy cm khng bnh thng c ngun gc di truyn trc mt phn t c.

V d: ngi thiu enzyme cholinesterase huyt thanh th c phn ng co c ko di v ngng th nht i vi mt lng sucinylcholin bnh thng.

"153

II.4. Tc dng c ln c th2. C quan ch Mt phn t cht c khng phi tc dng n mi c

quan u nh nhau. C quan ch l c quan thng c mt nhy cm vi phn t c ln hn hoc tp trung cao cc phn t c v/hoc cc cht chuyn ha ca n vng tc dng. Vic xc nh c quan ch ph thuc cc nhn t khc nhau:

Do s nhy cm ca mt c quan Do s phn b Do s hp thu chn lc Do s chuyn ha sinh hc

"154


2. C quan ch Do s nhy cm ca mt c quan Cc nron v c tim l nhng vng trao i nhanh

qua mng nn s hot ng ca chng ph thuc vo sn phm ATP t phn ng oxy ha ty th. Do vy, cc c quan ny rt nhy cm vi s thiu oxy khi c mt ca cht c. VD: Cacbon oxyd.

"155

II.4. Tc dng c ln c th2. C quan ch Do s phn b H thng h hp v da l nhng c quan ch ca cht c cng nghip hay cht c mi trng v chng c nhng vng hp th tng ng. VD: bis-clorometyl, va gy khi u da khi tip xc, va gy khi u h thng h hp khi ht phi.

Gan v thn c chc nng trao i cht v bi tit, nn rt nhy cm vi cc tc nhn c.

H thn kinh d b tc dng c vi nhng cht a bo nh metyl thy ngn, c th vt qua hng ro mu-no.

Tia cc tm tc ng trc tip ln da gy khi u da, do tnh xm nhp km. Trong khi , tia chiu x hoc tia ion c th i qua cc m lm h hng ADN v to ra khi u hoc gy bnh bch cu. "156


2. C quan ch Do s hp thu chn lc Mt s t bo c i lc ln i vi nhng phn t

nht nh. Mt s cht c i lc mnh, s tch t chn lc.

"157

II.4. Tc dng c ln c th2. C quan ch Do s chuyn ha sinh hc Gan l vng ch y ca cc chuyn ha sinh hc nn

nhy rt nhy cm vi tc ng ca cc cht c. Tuy nhin, mt s trng hp cht chuyn ha kh bn nn c ch chuyn sang mt c quan khc v gy c tnh y. VD: Bromobenzen c hot ha ti gan nhng gy c tnh thn.

Cc enzyme hot ha sinh hc, khng bt buc phi phn b ng u trong mi c quan hay trong mi t chc.

S thiu mt h thng gii c trong mt c quan nht nh cng s lm cho c quan tr thnh c quan ch.

"158

II.4. Tc dng c ln c th3. Receptor Khi nim v receptor Receptor l nhng protein mng (khu tr trn mng)

hoc protein ha tan (khu tr trong bo tng) c kh nng nhn bit v gn c hiu vi mt thc th l hay l ligand khi ng mt tn hiu sinh l trong t bo c lin quan.

Ligand c th l mt phn t nh (hormon, amin dn truyn thn kinh, alcaloid, mt vi loi ion), mt protein, mt polysacarid, mt axit nucleic hoc thm ch mt virus.

Receptor kt gn vi ligand nhng khng lm thay i cu trc ca ligand m ch nhn thng tin t ligand to nn mt hiu ng sinh hc mi.

"159

II.4. Tc dng c ln c th Khi nim v receptor Bn thn phn t receptor khng c hot tnh sinh hc

m n ch c hot tnh khi c kt gn vi ligand c hiu ca mnh.

S lng v tr receptor trong mi t bo thng khng nhiu v thay i theo loi t chc v ging ng vt. Cng mt loi receptor nhng s lng v tr khc nhau.

S phn b receptor trn mng t bo thng khng u nhng khi receptor gn vi ligand th chng chuyn nhanh v t tp vo mt vng no gy tc dng sinh hc cho c th.

"160


3. Receptor C ch tc dng ca cc receptor Chc nng ca receptor l ni ca h thng sinh

hc c kh nng nhn bit nhng cht ha hc xc nh v cm ng mt hiu ng sinh hc c trng sau khi kt gn vi nhng hp cht ny.

Hai c ch tc dng chnh ca receptor: Adenylate cyclase Dng Ca2+

"161

II.4. Tc dng c ln c th3. Receptor Tnh cht c bn ca receptor Nhn bit mt cch c hiu c tnh ca mt tc nhn. Sn xut ra mt hiu ng ha sinh hoc l sinh p

li tc nhn c ny. Trong c t hc, khi nim v receptor c m rng

thnh receptor phn t. Trong c t hc phn t, khi nim v receptor ny s rt ch li trong s hiu bit cc c ch tc dng ca phn t c.

Receptor phn t l nhng phn t sinh hc c cha nhng vng nucleophil. Phn ln cht c l nhng cht electrophil hoc tr thnh electrophil sau khi c chuyn ha sinh hc, do chng c th kt hp bng ng ha tr vi cc phn t sinh hc ny.

"162

II.4. Tc dng c ln c th4. Cc c ch tc dng ca cc cht c n cc

phn t sinh hc Tc dng c do to ra mt lin kt thun nghch Tc dng c ca mt tc nhn c da trn mt

lin kt thun nghch l lin kt phi ng ha tr cng ging nh tc dng dc hc ca mt s tc nhn thuc.

Trong kiu lin kt ny, cc hiu ng ca pha tip xc (hp th v phn b) thng c lin quan vi liu lng c, nng c, tc xut hin v mt i ca cht c.

y, yu t thi gian c xem l mt thng s quan trng v thi gian cng di lm ko di pha tip xc. "163


4. Cc c ch tc dng ca cc cht c n cc phn t sinh hc

Tc dng c do to ra mt lin kt bt thun nghch

Kiu lin kt ny thng lin quan n cc phn t c kh nng phn ng ha hc. Mc c thng ph thuc nhiu kiu phn t sinh hc c tip xc vi cht c.

Theo nguyn tc th cc cht c c hot ha trc khi tin hnh tc ng c v thng nhm vo ci ch l vng nucleophil (-NH2, -SH) ca cc phn t sinh hc.

"164


a. Hiu ng thi gian i vi mt tc nhn c tc dng bt thun nghch

th trn nguyn tc s khng tn ti mt liu lng gn c.

Tuy nhin, trong c th tn ti nhng h thng tu sa ca ADN hoc s tng hp mi cc protein. Cc h thng ny cho php loi b hoc chnh sa li cc phn t c cc lin kt ha sinh bt thng. Tuy nhin cc h thng ny vn b hn ch.

"165


b. Cc vng nucleophil Cc cao phn t sinh hc (ADN, ARN, protein) rt

giu cc vng nucleophil, l nhng cht tip nhn chn lc ca cc cht c electrophil.

Cc vng nucleophil ca cc protein ch yu l cc axitamin giu electron nh: histidin, cystein, lysin, tyrosin, triptophan, metionin. Cc axitamin ny thng phn ng vi cc cht gy ung th, nh: hydrocacbon, amin d vng, cc nitrosoalkylure

"166


c. Cc tc nhn alkyl ha Cc cht c c hot ha trc khi chuyn chng

thnh dn xut electrophil tc dng c vi cc vng nucleophil ca cc cao phn t.

V d: Cc hydrocacbon thm thng c chuyn ha bi monoxygenase P-450 ca vi th gan thnh dn xut trung gian diolepoxyd rt hot ng, c kh nng phn ng vi cc nhm SH ca protein.

"167

Tc dng c do to ra mt lin kt bt thun nghchd. Cc dn xut N-nitro y cng l cc dn xut ca cc tc nhn alkyl ha,

nhng chng cn c quan tm v x l ring v y l nguy c tim n khi c mt chng trong thc phm.

Cc nitrosamin thng khng trng thi t do trong mi trng m c hnh thnh bng con ng ni sinh t cc nitrit v cc amin hoc t cc vi khun. Ngc li, cng nh cc vi khun cc nitrosamin c kh nng b ph hy thnh cc amin v nitrit:

HNO2+ H+Nitrit acid acid nit

2HNO2 N2O3 + H2O acid nit anhydrit nit "168


d. Cc dn xut N-nitro Khi c mt amin (bc 2 hoc bc 3) th N2O3 s nit

ha cc amin ny, tc nitro ha cc i thng pH 3 3,4 m tai acid nitr b ion ha n 50% (pKa = 3,36):

R

R

R

RNH + N2O3 N=NO + HNO2

amin anhydrit nitr

"169

Tc dng c do to ra mt lin kt bt thun nghchd. Cc dn xut N-nitro Nhng, s to thnh nitrosamid khng phi

anhydrit nitr l tc nhn nitr ha m c th l ion nitr acid (H2NO2+), t l nitro ha khng xy ra pH ti u m cc amid thng t l vi nng ion hydro v nng ion nitrit:

HNO2+ H+Nitrit acid acid nit

HNO2acid nit anhydrit nit

+ H+

N=OR-N-CO-R + H2O + H+R-NH-CO-R

+ H2NO2amin nitrosamid

"170


phn t sinh hc Tc dng c do hnh thnh cc gc t do Gc t do l mt thc th ha l c th tn ti di

dng mt nguyn t hoc mt phn t mang mt electron khng cp i. Gc t do thng c to ra do s phn ct ng ly mt phn t:

R-H R + H V d: Mt s nhm c cht c tc dng c do c

ch gc t do nh paraquat, oxy cao p, ozon, cc peroxyd, cc hydrocacbon a vng, nitrosamin, cc dn xut nitro.

"171

Tc dng c do hnh thnh cc gc t do

Gc t do c 02 c im: C th ly electron t phn t khc, lm cho phn t tr thnh gc t do mi:

A* + B: A: + *B Gc t do trng thi trung ha khi ghp electron

khng cp i ca gc ny vi electron khng cp i ca gc khc. S to ra gc t do l ngun gc ca s peroxyd ha cc lipid lm h hng thc phm c cht bo.

"172


phn t sinh hc Tc dng c do to thnh superoxyd v cc

dn xut ca n Superoxyd c th l cht oxy ha (nhn electron), va

l cht kh (cho electron). Superoxyd c sinh ra thng thng qua phn ng

ha sinh c bn: Oxy phn t tr thnh superoxyd theo phn ng:

O2

e- RNO2"173

Tc dng c do to thnh superoxyd v cc dn xut ca n

Hp cht paraquat v cc dn xut nitro hu c (nh nitrophenyl, nitrofuran, nitroimidazol) l nhng cht ht electron rt mnh. Phn ng thng c tin hnh thng qua mt dn xut nitro gc lm trung gian, sau gc ny mi nhng electron c thn ca mnh cho oxy phn t.

Sn phm superoxyd t tham gia phn ng do c kim sot bi enzyme superoxyddismtase:

Superoxyddismutase2H+ + + H2O2 + O2

"174


phn t sinh hc Tc dng c do s giam gi l hc cc cht c Nhiu cht c nh thuc bo v thc vt, kim loi

nng, biphenyl polyhalogenua, cc cht do t bao b i vo c th qua con ng n ung. Cc tc nhn ny thng k nc, khng b phn gii bng sinh hc nn tn lu trong mi trng v c tch t li trong sinh khi.

Trong trng hp giam gi l hc, hng s tc thi loi ca ton h thng, c biu th bng h thc sau:

"175

Tc dng c do s giam gi l hc cc cht c Th tch phn b biu kin thng c tnh qua

thng s: !!!

Th tch phn b biu kin thng c tnh qua thng s: !

Co l nng ban u ca cht c thi im To. S thanh thi ca cc hp cht a bo (k nc) l

rt nh v th tch phn b biu kin ca chng li rt ln nn s thi loi ca cc hp cht ny i hi mt thi gian rt di.

S thanh thi thn S thanh thi ganKe =

Th tch phn b biu kin

0,693T1/2

=

Liu lngCo

"176


phn t sinh hc Tc dng c do to thnh methemoglobin ng vt c v v ngi, oxy c kh nng kt gn

thun nghch vo protein kim loi hemoglobin. Tuy nhin, oxy ny ch gn kt hemoglobin ang trng thi st hai (Fe2+) to thnh phn t cha st trng thi oxy ha c tn gi l methemoglobin, trng thi oxy ha ca st ba (Fe3+) khng cho php hemoglobin kt gn c oxy.

Khi a vo h tun hon mu mt cht c kh nng oxy ha nguyn t st th s gy ra mt lng methemoglobin mu.

"177

CH 3. NH HNG CA C CHT THC PHM LN CC C QUAN QUAN TRNG CA

C THIII.1 nh hng c cht trong huyt hc III.2

nh hng c cht n gan III.3 nh hng c cht n thn III.4nh hng c cht n thn kinh III.5

III.6

III.7

nh hng c cht n da v mt nh hng c cht n phi

nh hng c cht n h thng min dch

178

nh hng ca c cht ti ch v ton thn khi tip xc

Tc dng ti ch l c tnh xy ra ngay ti ni tip xc vi cht c: cc cht n mn gy tn thng ng tiu ho khi ung.

Tc dng ton thn xy ra sau khi cht c c hp thu vo tun hon s gy tn thng cho h thn kinh trung ng.

Phn ln cc cht c h thng s ch gy c cho mt vi c quan ch v c quan ch cha hn l ni tch ly nhiu cht c nht. Theo th t, tc dng c thng xy ra h thng thn kinh trung ng, mu, h to mu, gan, thn, phi.

"179

Tc dng c ton thn

S ha cht tc dng c trong c th ng vt v con ngi

"180

III.1. nh hng c cht trong huyt hc Cht c tc ng trc tip ca n cc t bo ty

xng lm gim hoc ngng sn sinh t bo mu. Qu trnh tng hp huyt sc t c th chu tc ng

ca cht c theo mt s c ch sau: Gim tng hp huyt sc t hoc tng lng tin

thn huyt sc t dn n tnh trng thiu mu, t dn n ri lon chuyn ha porphyrin.

St trong hemoglobin c th b oxy ha t st ha tr II thnh st ha tr III, to thnh methemoglobin khng c kh nng vn chuyn oxy.

Qu trnh oxy ha lm bin cht hemoglobin, to ra cc th Heinz lm tng c 2 qu trnh thc bo hng cu v tan mu t nhin.

"182

III.1. nh hng c cht trong huyt hc Cc thnh phn huyt tng, hng cu, bch cu v

tiu cu trong mu u c th b thay i di tc dng ca cht c:

Huyt tng: Cc thuc m lm gim pH, h thp d tr kim v tng kali ca huyt tng.

Hng cu: S lng hng cu trong mt cm3 tng ln trong trng hp ng c gy ph phi do huyt tng thot ra nhiu nn mu b c li. Trng hp khc hng cu c th b ph hy hoc b mt kh nng vn chuyn oxy nn c th b ngt.

Bch cu c th b gim hoc tng v s lng. Tiu cu: c khi b gim n vi chc nghn n v.

"183

III.1. nh hng c cht trong huyt hc S hnh thnh ca mu

"184

III.1. nh hng c cht trong huyt hc T bo bch huyt (t bo B v T)

"185

Tc dng c ca cc hp cht c gc amin v nit thm gy hin tng thiu mu do hnh thnh Methemoglobin

Tc ng n mng lipid hoc protein ca t bo hng cu gy bin i v hnh thi t bo.

"186

Mt s c cht gy ra cn bnh v ty xng Benzen Procainamide Methyldopa Sulfasalazine Isoniazid Diphenylhydantion Pentachlorophenol Cephalothin Sodium valproate

Chloramphenol Allopurinol Sulindac Sodium valproate Phenylbutazone Tolbutamide Alkylating v antimetabolite Gold Carbamazepine

"187

S chuyn ha ca benzen Nhng cht chuyn ha ca benzen l nguyn nhn

gy ra cn bnh bch cu.

"188

III.2. nh hng c cht n h thng min dch H min dch vn l hng ro quan trng bo

v c th trnh khi cc loi virus gy bnh. Tuy nhin, c 2 nhm bnh lin quan n h min

dch: Nhm 1, do sc khng c th yu nn virus tn cng vo ngi. Nhm 2, nguy him hn, l bnh t min, ngha l bnh do chnh h min dch ca c th sinh ra nhng cht quay tr li tn cng vo cc m ca c th.

"189

III.2. nh hng c cht n h thng min dch

C ch min dch t nhin

"190

Tm hiu H min dch ti Link https://www.youtube.com/

watch?v=cSHT6fHzxMA

C ch min dch t nhinCc c ch c hc v ho hc Ba v tr tip xc gia c th v mi trng bn ngoi

l da, ng tiu ha v ng h hp. C ba ca ng ny u c che ph bi cc biu m ni lin vi nhau c tc dng nh nhng hng ro sinh l ngn cn khng cho vi sinh vt xm nhp.

Cc t bo biu m cn to ra cc cht khng sinh c bn cht l cc peptide c tc dng tiu dit vi khun.

Ngoi ra biu m cn c mt loi t bo lympho trong biu m (intraepithelial lymphocyte). Cc t bo lympho trong biu m c coi nh ngi gc cng ngn khng cho cc tc nhn nhim trng xm nhp qua cc biu m.

"191

C ch min dch t nhinCc c ch t bo ca h min dch Hai loi t bo lm nhim v thc bo trong mu l

cc bch cu trung tnh v cc t bo mono. y chnh l cc t bo mu c iu ng n cc v tr c nhim trng nhn din ri nut v phn hy cc vi sinh vt .

Cc t bo git t nhin (t bo NK): Cc t bo NK c kh nng nhn din v tiu dit cc t bo bt thng ca c th (b bin i do nhim vi sinh vt hoc do chuyn dng thnh t bo ung th), nh cc khi u c tnh khng th hnh thnh.

"192

C ch min dch t nhinCc c ch th dch ca h min dch H thng b th l mt tp hp cc protein gn trn

cc mng v protein lu hnh trong h thng tun hon, c vai tr quan trng trong khng chng vi sinh vt. B th c kh nng bt gi, ph hy, tiu dit vi sinh vt v c kh nng hp dn ha hc lm cho cc t bo bch cu trung tnh v cc t bo mono di chuyn ti, thc y phn ng vim ti ni din ra hot ha b th.

Khi c cc vi sinh vt xm nhp, cc i thc bo v cc t bo khc p ng li bng cch ch tit ra cc protein c gi l cc cytokine c tc dng tham gia vo rt nhiu tng tc gia cc t bo vi nhau trong p ng min dch t nhin. "193

III.2. nh hng c cht n h thng min dch

Tc dng c lm gim chc nng h min dch: y l phn ng ca c th i vi cc cht c

cng nghip v c t t nhin. Cc cht c ny nh hng n c min dch dch

th v min dch t bo gin tip, gim tng hp khng th, ngn cn b th v mt s qu trnh khc.

Chc nng trung tnh ca t bo lympho thay i v g im s h nh thnh t bo l ympho (lymphoblastogenesis).

"194

III.2. nh hng c cht n h thng min dch T bo min dch lympho

"195

III.3. nh hng c cht n gan Gan l mt c quan nm ng t ng tiu ha. T

tnh mch ca, gan nhn tt c cc cht do chuyn ha thc n cung cp v cc cht c. Mt khc, cc cht cha trong mu qua h thng i tun hon u tc dng n gan. !!!!!

Vai tr ca gan: Lu tr st Cn bng hormone Sn xut cc yu t min dch.

"196

III.3. nh hng c cht n gan Cu trc gan, ch ra cc mch mu ca t bo gan

Tnh mch trung tm

Khe h hnh sin

Lp ganL hng ca

gan

ng mt nh

ng mtng mch

Trc tnh mch"197

III.3. nh hng c cht n gan

H thng tun hon mu duy tr s sng ca gan.

Hu nh trng hp ng c no cng gy tn thng gan. Tm hiu chc nng

gan ti Link https://www.youtube.com/watch?v=clEH4M8KHmk

"198

III.3. nh hng c cht n gan Tn thng gan

"199

"200

T bo gan b tc ng bi c cht (Acetaminophen) gy ra hin tng hoi t t bo gan.

Mt s cht ha hc gy hoi t gan Acetaminophen Aflatoxin Alkyl alcohol Arsenic, inorganic Botulinum toxin Bromobenzene Chlorobenzens Chloroform Dichlorpropane Dioxane DDT

Dimethylntrosamine Dinitrobenzene Dinitrotoluene Methylchloroform Naphthalene Paraquat Phalloidin Pyridine Thioacetamide Urethane Xylidine

"201

Cc loi tn thng gan Thoi ha t bo gan v

t vong. Oxy ha lipid Ct lin kt bt thun

nghch ca i phn t Thiu Calcium Gim min dch M trong gan X cng ng mch Tn thng mch mu X gan U bu

Mt s c cht gy tn thng gan:

Ampicilin Arsenicals, organic Chloropromazine 4,4-Diaminodiphenylamine Methyltestosterone Estrogens Ethanol Paraquat Phenytoin Tolbutamide"202

Cc loi tn thng gan Cc giai on tn thng gan

"203

nh gi tn thng gan Da trn triu chng xy ra v tc dng c cp

tnh hay mn tnh ca gan gm hoi t t bo gan, tn thng cc mch mu trong gan, dp v mt hoc s xut hin ca khi u c tnh.

nh gi hnh thi ca gan bng cch soi sinh thit m t bo gan trn knh hin vi.

Kim tra mu: c m t qua php o cng sut lm vic theo chc nng ca gan hoc o lng ni bo gan c trong mu.

"204

Nhn bit triu chng ung th gan Mt cm gic n ngon ming, bing n. n ung kh tiu, bun nn, i ma, au bng. Ngi yu v mt mi, kh chu. D chy mu hay d c vt bm. Cm gic nng v au di b sn phi. Vng da tng dn, mng nhy v mt c mu hi

vng. Bng bj chng to.

! Tuy nhin, cc triu chng thng m h, khng

r rng."205

Cch phng nga ung th gan

Hn ch ung bia ru. Hn ch cc thc phm c hm lng cht bo

cao. Trnh tip xc trc tip hay s dng thc phm c

cha cc ha cht c hi nh thuc bo v thc vt, cht ty ra kh trng, nm mc

Tim nga vaccin vim gan B. Khm sc khe nh k nhm pht hin bnh sm.

"206

III.4. nh hng c cht n thn H thng bi tit thn ngi: (a) h thng bi tit hon

chnh, (b) mt ct ca thn, (c) mt ct thn phng to v tr c

"207

(c) mt ct thn phng to

"208

III.4. nh hng c cht n thn

Vai tr ca cu thn: iu chnh ni tit, bi tit cht cn b sinh ra trong qu trnh chuyn ha, iu chnh kim toan v iu ha in gii, tham gia to mu, iu ha chuyn ha canxi, iu ha huyt p...

"209


S bi tit qua nc tiu l php o da trn ba tin trnh thc hin thn: S lc qua cu thn (GF: glomerulus filtering) S thm ht tr li qua ng thn (TR: tubular

reabsorption) S bi tit qua ng thn (TS: tubular secretion)

T l cht bi tit c thi qua b phn cu thn v ng thn ph thuc vo c cht trong plasma, cn t l hp th tr li qua ng thn nh ph thuc vo c cht trong nc tiu.

"210

S bi tit cht c vo nc tiu qua thn

"211

Tm hiu Qu trnh lc mu to nc tiu n v chc nng ca

thn ti Link https://www.youtube.com/

watch?v=LCfwsW_crEU

III.4. nh hng c cht n thn Gan l ni u tin m mu n t d dy v rut.

Nhng sau mu ri khi gan n tim v c bm trc tip n thn. Thn c nhim v iu ha s cn bng gia nc v mui trong c th, ngoi ra thn cn c vai tr quan trng trong vic kh cht c.

C th ni cng vic chnh ca thn l ly tt c mu trong c th v lm sch n:

1

Lc mu gi li mu sch trong t bo

2

Hp th li nc lc v cht dinh dng cn thit

3

Cht c c bi tit sau khi c lc, loi qua nc tiu

"212


Nh vy, mu sau lc cha nc v cc cht ha tan, v sau lc nc v cc cht ny c hp th tr li vo mu. Tuy nhin, mt vi cht ha tan trong mu b bi tit vo trong nc tiu.

Reabsorbed Secreted

Sugar, sodium, vitamins, nutrients, water

Hydrogen ion, potassium, ammonia, drugs, toxins

"213

III.4. nh hng c cht n thn Mt s triu chng tn thng thn

"214 Suy thn

Si thn

Ung th

nh gi tn thng thnXc nh t l cht bi tit ca c cht trong thn

l mt bin php chun on h s bnh n v tnh trng chc nng ca thn: Ua: hm lng cht trong 1ml nc tiu V: th tch nc tiu thi ra trong mt n v thi

gian. Pa: hm lng cht trong 1ml plasma Cl: lc ca cht trong mt n v thi gian

"215

nh gi tn thng thn V d 1: o lc ca inulin mt polymer ca

fructose vi trng lng phn t 5200 daltons. Php o hm lng inulin trong cu thn l mt trong nhng tiu chun o cn bng cht trong c th. U = 31 mg/ml V = 1,2 ml/min P = 0,3 mg/ml !!! ngi trng thnh bnh thng c lc

inulin khong 125 ml/min"216

nh gi tn thng thn

Xc nh t l cht thi, nh gi c tn thng ca thn: !!!!

T l cht thi, xc nh bi lc ca cht o c trong mt n v thi gian v lc cht cho php i vi c th ngi bnh thng.

"217

nh gi tn thng thn

V d 2: p-aminohippuric acid (PAH) - mt acid hu c

Hm lng PAH trong 1ml plasma (PPAH), hm lng PAH trong 1ml nc tiu (UPAH) v th tch nc tiu thi ra trong 1 pht (V). S dng cng thc tnh Cl, ta c c lc PHA (ml/pht). T ta c th xc nh c t l PAH c thi ra, khi ta bit n ng trng thnh c sc khe tt t khong 650 ml/pht.

"218

nh gi tn thng thnT l cht thi < 1

! Th hin cht c khng c lc hon ton, c

th do cht c c bi tit ra v sau c hp th ngc tr li.

T l cht thi > 1 !

Th hin cht c c lc v o thi hon ton.

"219

Nhn bit triu chng suy thn

Suy thn mn tnh c xc nh khi c s bt thng v cu trc hoc chc nng thn, c th c protein trong nc tiu, tng creatinin mu, mc lc cu thn gim, m hc thn thay i.

Khi thn b suy thn, cc chc nng hot ng gim, dn dn dn n mt chc nng khin bnh nhn t vong do nhim toan, tng kali mu, suy tim, ph phi, tai bin mch mu no.

Bnh thn mn tnh lin quan nhiu n bnh tng huyt p, bnh l tim mch, gt, i tho ng v cc bnh nhim khun, nhim c.

"220

Cch phng nga suy thn mn tnh

Ch s dng thc phm an ton. !

Cc bin php iu tr suy thn ph bin v hiu qu hin nay ang c thc hin l lc mu chu k v ghp thn. Tuy nhin i vi mi phng php u vp phi nhng kh khn ring.

"221

III.5. nh hng c cht n thn kinh

"222

III.5. nh hng c cht n thn kinh C ch tc dng trn h thn kinh: Khi c mt cht c trong c th, n c kh nng tc ng n h thn kinh thng qua phong ta s dn truyn xung thn kinh do cht trung gian ha hc ca qu trnh c ch cung phn x. Kt qu l c th khng iu khin c cc phn x v kt thc bng cc cn co git v t lit.

Cht c c th lm thay i tnh thm ca mng t bo thn kinh i vi cc ion. Cc dng natri v kali b cht c lm thay i, dn n thay i ngng tc ng trn mng t bo.

Cht c c ch cc enzyme thit yu cho chc nng cn bng, lm thay i c tnh dn truyn qua xung thn kinh."223

Truyn dn xung thn kinh

"224

S truyn dn xung thn kinh (a) in th ha hc in t ca t

bo xung thn kinh trng thi ngh.

(b) Trng thi kch thch s thm dng Na+ ca xung thn kinh.

(c) Bt u kh cc, tng tnh thm, cho php Na+ vo bn trong t bo xung thn kinh tt.

(d) Bt u ti phn cc ging nh xung lc ban u. Cc dng tch in bn trong t bo cao, tng tnh thm dng K+ i ra ngoi t bo v thit lp in th trng thi ngh.

(e) Tip tc ti phn cc xung thn kinh n khi hon thnh chu trnh."225

S kch thch nron truyn dn xung thn kinh t t bo ny sang t bo gia khp ni t bo thn kinh.

Nron truyn dn xung thn kinh c phng thch v kch thch receptor, lm tng mc cAMP, nh hng n hot ng ATPase, Na/K v gradient in t ha hc thm qua mng t bo.

S kch thch kt thc khi acetylcholinesterase b ph hy (hoc hp thu li epinephrine vo dy thn kinh).

"226

Truyn dn xung thn kinh qua synap

"227

Tm hiu Qu trnh truyn dn xung thn kinh ti Link https://www.youtube.com/watch?v=ciCuzJoxVGc

Cc loi Synap thn kinh

A: Synap thn kinh - thn kinh

B: Synap thn kinh - C

C: Synap thn kinh - Tuyn

"228

Tm hiu Qu trnh truyn dn xung thn kinh qua cc nron ti Link https://www.youtube.com/watch?v=Sf3H8EuaVSU Tm hiu Cung phn x vn ng ti Link https://www.youtube.com/watch?v=D1wJP30Sl4g

III.5. nh hng c cht n thn kinh C ch gy tn thng h thn kinh trung ng

hoc h thn kinh ngoi vi nh hng n chc nng nron v dn truyn trc thn kinh. Nhng tn thng thn kinh ny thng l mn tnh v c th l vnh vin.

Hoi t nron l do tc ng trc tip hoc gin tip ca cht c n cc nron. Tc ng trc tip: cc hp cht thy ngn hu c

lm suy yu s tng hp protein thn kinh thit yu. Tc ng gin tip: thiu oxy m do cacbon

monooxide hay cyanide gy tn thng thn kinh th pht.

"229

III.6. nh hng c cht n da v mt Da Da l t chc kh phc tp, m da l mt khi

tng hp gm 3 lp: Biu b, trung b v h b kt hp cht ch vi nhau thnh cc lp t chc bao ph mang tnh cht chun dn (v cc pha), c tnh nht, tnh to hnh, c cc lp biu m, cc m lin kt, cc tuyn, lng v gc lng, th c, tn cng cc dy thn kinh, li mch mu v bch mch.

Cc t bo biu b lun lun thay th mi hon ton trong 4-6 tun. Nh th da l mt trong cc loi m lun sinh trng nhanh ca c th.

"230

Da Lp biu b ca da

(Epidermis): Dy t 0,07 1,8 mm, l lp ngoi cng, c chc nng bo v c th.

Lp trung b (Dermis): Dy t 0,7 7 mm, l mt lp x rt chc.

Lp h b (Hypodermis): Dy t 0,25 n hng cm, l m lin kt m.

"231

Mt s bnh v da do c cht

Cht lp biu b, do tip xc trc tip vi ha cht c hi khong 25-30%, thm ch cao hn n 75%, gy bng mt mng ln trn c th. Lp biu b mt i, lp trung b c th b tn thng, nhng n c kh nng chng s xm nhp ca ha cht v gy nhim vi sinh vt.

Bnh vim da, ni cc nt mn ty khp mt, au nhng khng c. y l do c s tch ly cc cht du to nhn tit ra qua da, gy tch t to cht sng v bt kn l chn lng v tuyn nhn. Mt s ha cht halogen nh polyhalogenate naphthlene, biphenyl, dibenzofuran, polychlorophenol v dichloroaniline, l nguyn nhn gy ra mn.

"232

III.6. nh hng c cht n da v mt Mt Mt l c quan th gic, gm 2 con mt c kch thc

nh. Mi con mt l mt khi cu dai c ng knh chng 2,5 cm.

Chc nng ca mt l xc nh cc i tng nhn, tp hp v hi t tia sng t i tng, sau truyn hnh nh r nt n cc t bo nhy cm nh sng nm y mt, ni hnh nh c thu nhn v bc u c x l.

Hnh nh sau c chuyn ti bi xung in dc theo dy thn kinh th gic (l dy thn kinh i t y mt ln no). Cc dy thn kinh th gic lin kt vi nhau trong no b cho php chng ta nhn thy c nhng hnh nh kt hp t c hai mt."233

Mt Phn no b ghi nhn cc tn hiu th gic ny c gi

l v no th gic, nm pha sau cng ca no b. T v th gic, tn hiu c truyn n nhiu phn

khc ca no. Cc xung in ban u phi tri qua mt qu trnh x l phc tp to ra nhng hnh nh m chng ta nhn thy.

"234

Mt s bnh mt ha cht

Hu nh bnh v mt do ha cht l bt cn lm vng te ha cht hoc ha cht bay hi vo mt. Dung mi hu c gy ra nguyn nhn ph hy cht bo v protein trong mt, gy ra mt s bnh mt nh tn thng gic mc, thy tinh th, vng mc.

Ngoi ra, c kh nng gy ra hin tng nhn p cao bt thng. Nu p lc trong nhn cu qu cao, n c th gy tn thng dy thn kinh th gic ngay ti im m dy thn kinh th gic i ra khi mt.

Tt c cc trng hp trn u c kh nng gy ra m la."235

III.7. nh hng c cht n phi Cc cht c xm nhp vo c

th qua ng h hp c th gy ra: Ti ch nh ho, km theo chy

nc mi, nc bt. V d: cc hi c, hi ngt.

Tc dng ton thn nh kh CO gy tm ti.

Cht c c ch h hp gy ngt th tin ti ngng th nh thuc phin, cyanic, thuc ng. Mt s cht c th gy ph phi nh: hydrosulphit, photpho hu c.

"236

III.7. nh hng c cht n phi

"237

CH 4. TC DNG C CA CC C CHT, C T THC PHM LN C TH

IV.1 Tc dng c ca cc cht c c sn trn nguyn liu v hnh thnh trong qu trnh BQ-CB

IV.2 Tc dng c ca mt s ph gia v cht h tr k thut

IV.3 Tc dng c ca d lng thuc bo v thc vt v thuc th y IV.4 Tc dng c ca kim loi nng

238

IV.1. Tc dng c ca cc cht c c sn trn nguyn liu v hnh thnh trong qu trnh BQ-CB

Mt s c cht c sn trong nguyn liu ng vt

1. Tc dng c ca Tetrodotoxin Tetrodotoxin (Puffer Fish Poisoning) l mt loi c t

thn kinh mnh nht tm thy trong da, gan, c tht, c bit rt nhiu trng mt s loi thy sn, nh: C nc (Tetraodontidae, thuc h Pufferfish), Bch tuc m xanh (Hapalochlaena maculosa), Cua (Eriphia spp.), c (Pimple Nassa), ch (Atelopus spp.), To (Jania spp.)...

"239

Mt s c cht c sn trong NL ng vt1. Tc dng c ca Tetrodotoxin

Bnh thng c t ny tn ti dng tin c t tetrodomin khng c, khi c b p cht hoc b n th tetrodomin s chuyn ha thnh tetrodotoxin gy c.

"240

Mt s c cht c sn trong NL ng vt1. Tc dng c ca Tetrodotoxin

C ch tc dng c: Tetrodotoxin gy c ch cc knh Natri ca t bo, ngn chn dng Na+ trong c ch bm Kali-Natri. Khi , knh Natri ca t bo thn kinh b c ch, lm ri lon hot ng ca t bo v s truyn dn xung thn kinh.

Triu chng nhim c: T, nga mi v pha trong ming, yu, lit c honh v c ngc, h huyt p, triu chng xy ra sau 10 pht v dn n t vong sau 30 pht.

"241

Cc h nc (Tetraodontidae, thuc h Pufferfish) Carinotertraodon travancoricu

s, Dwarf puffer Tetraodon miurus,

Congo puffer Tetraodon duboisi , Stanley-

pool puffer Takifugu ocellatus,

Peacock puffer Tetraodon erythrotaenia, Red-

banded puffer Tetraodon schoutedeni,

Congo-spotted Puffer Tetraodon turgidus,

Brown puffer"242

Cc h nc (Tetraodontidae, thuc h Pufferfish) Arothron reticularis,

Reticulated pufferfish Tetraodon biocellatus,

Figure eight Tetraodon suvattii ,

Pignose puffer Takifugu niphobies,

Grass Puffer Tetraodon lineatus,

Fahaka puffer Takifugu oblongus,

Lattice Blaasop Carinotetraodon lorteti,

Crested puffer"243

Cc h nc (Tetraodontidae, thuc h Pufferfish)

Sphoeroides testudineus, Turtle puffer

Carinotetraodon salivator, Striped Redeye puffer

Tetraodon miurus, Congo puffer

Carinotetraodon irrubesco, Red-tailed Redeye puffer

Tetraodon cochinchinensis , Target puffer

Tetraodon mbu, Giant puffer

"244

Cc h nc (Tetraodontidae, thuc h Pufferfish)

Tetraodon palembangensis, Real Palembang puffer

Tetraodon nigroviridis, Green puffer

Tetraodon leiurus, Eyespot puffer

Auriglobus silus, Eiongated Golden puffer

Colomesus psittacus , Parrot puffer

Tetraodon fluviatilis, Ceylon puffer

"245

c (Pimple Nassa)

Bch tuc m xanh (Hapalochlaena maculosa)

"246

Cua (Eriphia spp.)

Eriphia gonagra Eriphia verrucosa Eriphia ferox Eriphia granulosa

"247

ch (Atelopus spp.)

"248

To (Jania spp.)

"249

CH THO LUN 1: Tc dng c ca Tetrodotoxin ln h thn kinh trung ng

! Bn cht Ngun gc Kh nng tc dng c?

Tin trnh xm nhp phn phi trao i o thi trong c th?

C ch tc dng c? Gii thch phn tch c ch tc dng c Phng tr c?

"250

Tho lun trnh by ti lpC ch vn chuyn ion ca mng t bo? V m hnh th hin c ch bm ion Natri? Th hin r cc tc dng c ca Tetrodotoxin

ln t bo v ty th trn m hnh? Gii thch s tt nghn xung thn kinh, gy ra

kh nng t lit h thn kinh trung ng?

???

"251

c t sinh hc bin2. Tc dng c ca CFP (Ciguatera Fish Poisoning )

Ciguatoxin c sn sinh bi mt loi

Gambierdiscus toxicus v c tm thy trong gan, c, da v xng ca nhiu u trng c n to (Chinain v

cng s, 1999; Lehane v Lewis, 2000).

"252

ttt

"253

c t sinh hc bin2. Tc dng c ca CFP CFP tc ng ln knh vn chuyn ion ca mng

t bo. Khi ciguatoxin tc ng ln knh Natri, Na+ c chuyn vo ni bo nhiu hn, gy ra:

- T bo v ty th trng phng ln, xut hin cc mn nc trn b mt t bo.

- Gy ra chng tc nghn cc xung thn kinh. Nn nhn t vong do t lit h hp.

- i vi tim mch, tc ng ca ciguatoxin c lin quan n s co tht ca c tim.

Ciguatoxin c kh nng tc dng c ln t bo biu m rut, gy ra tiu chy.

"254

c t sinh hc binTc dng c ca CFP

Triu chng nhim c: Sau khi tiu th c b nhim ciguatoxin, triu

chng u tin c th din ra sau 30 pht. Mt s ca nh c th din ra sau 24 - 48 gi. Sau 30 pht nhim c, h thng tiu ha v

thn kinh mt i trng thi t nhin, gy bun nn, au bng v tiu chy. Cc triu chng v thn kinh bao gm nga

mi, tay, chn, nhit ln ln, mt kh nng vn ng, au c, au khp, au u v co git. i vi tim mch th gy kh th, nhp tim

chm, huyt p thp."255

c t sinh hc bin3. Tc dng c ca PSP (Paralytic Shellfish

Poisoning ) PSP tch t nhiu trong cc loi nhuyn th

khi chng n phi nhng loi to c cha c t ny v chng c sn sinh ra ch yu t loi to Dinoflagellates thuc ging Alexandrium, cc loi to ny phn b ch yu vng bin nhit i v n i.

Nhm c t PSP gm 30 cht c cu trc gn ging nhau. c t PSP u tin c xc nh v mt ha hc l saxitoxin (STX) v c xem l c t mnh nht trong nhm.

"256

c t sinh hc binTc dng c ca PSP Qu trnh chuyn ha c t

Trong chng loi Cnh tranh

Nui dngMm

bnh

"257

c t sinh hc binTc dng c ca PSP Chui thc phm nhim Saxitoxin (PSP)

"258

c t sinh hc binTc dng c ca PSP

C ch tc dng c: Khi PSP tc ng vo knh Na+, lm ngn cn ion Na+ i qua mng t bo thn kinh, v vy nh hng n vic truyn thng tin ca h thn kinh. S ngn cn ny s lan rng dn v ngn cn s truyn xung gia h thng thn kinh ngoi bin v cc c, dn n gy lit c.

Ngoi ra, PSP cn c ch enzyme Cholinesterase, l enzyme rt quan trng i vi h thn kinh.

"259

ff

"260

c t sinh hc binTc dng c ca PSP

Triu chng nhim c: Gy nga, tai, t mi phn ln trong

vng 30 pht, trng hp nh th b nha mt.

Trng hp hi nng th ni khng r rng, kh th.

Trng hp nng th c t lan rng ton thn v lit c, th kh hn, thng cht trong vng t 2 24 gi t lc nhim phi (Mons v cng s, 1998).

"261

c t sinh hc bin4. Tc dng c ca DSP ((Diarrhetic

Shellfish Poisoning) DPS l mt polyether bn nhit, bao gm 3

nhm chnh. Nhm th nht l c t acid, nhm ny bao

gm acid Okadaic (OA) v dn xut ca n c tn dinophysistoxin (DTX).

- OA v DTX c tch ly trong m m ca nhuyn th, cc hp cht trn c kh nng c ch phosphatase gy ra bnh tiu chy con ngi (Van Apeldoorn cng s, 1998; Hallegraeff v cng s, 1995).

"262

c t sinh hc binTc dng c ca DSP

Nhm th hai l c t trung tnh, bao gm cc polyether-lactones ca nhm pectenotoxin (PTX).

Nhm th ba c gi l yessotoxin (YTX), v dn xut 45-hydroxyyessotoxin (45-OH-YTX) (Draisci, 1996; Van Egmond, 1993).

Hai nhm c t ny ca phc hp DSP c kh nng gy c rt cao, c kh nng gy cht chut th nghim. Nhng, PTX c kh nng gy tiu chy thp v YTX khng gy tiu chy.

"263

c t sinh hc bin Tc dng c ca DSP

Triu chng nhim c: Cc triu chng c kh nng xy ra i vi con ngi khi nhim c DPS l tiu chy, bun nn, au bng, lnh nhng khng gy cht.

Thi gian bt u au thng t 30 pht n 12 gi sau khi nhim c v gim au trong vng 48 gi, phc hi hon ton sau 3 ngy.

(Asomata v cng s, 1978; Viviani, 1992; Aune v Yndstad, 1993).

"264

c t sinh hc bin5. Tc dng c ca NSP ((Neurologic

Shellfish Poisoning ) c t NPS cn c gi l brevetoxin, khng

mi, khng v, chu nhit v acid tt, ha tan c trong lipid.

Mt s chng Gymnodinium breve sn sinh ra neurotoxin c gi l brevetoxin (Viviani, 1992).

Ngoi ra, mt s neurotoxin khc cn c sn sinh bi cc loi to khc nh: Chattonella antiqua , Fibrocapsa japonica , Heterosigma akashiwo, Chattonella marina (Marine biotoxin, FAO, 2004)."265

c t sinh hc bin Tc dng c ca NSP C ch tc dng c: Brevetoxin

l mt cht kh cc, tc ng ln knh ion trong mng t bo, lm thay i tnh cht ca mng b kch thch theo hng tng cng dng ion Na+ i vo trong t bo.

Brevetoxin c th lin kt c hiu vi mt v tr s 5 trn cng ca knh Na+, gy ra s phng thch cc thng tin thn kinh. Bn cnh brevetoxin cng ph hy acetylcholine gy co c (Fleming and Baden, 1999).

"266

c t sinh hc bin Tc dng c ca NSP

"267

c t sinh hc bin Tc dng c ca NSP

Triu chng nhim c: Triu chng nhim NSP xut hin sm t

30 pht n vi gi thm ch vi ngy. Cc triu chng bao gm bun nn, tiu

chy, n lnh, v m hi, ln ln nhit , gim huyt p, ri lon nhp tim, t lit, nga mi, mt v t chi, chut rt, lit c, hn m nhng khng gy cht (Cembella v cng s, 1995; Fleming v cng s, 1995; Tibbets, 1998).

"268

c t sinh hc bin6. Tc dng c ca ASP ((Amnesic Shellfish

Poisoning) Domoic acid (DA) c xc nh ln u tin vo

nhng nm 1950 t loi to Chondria armata (Ravn, 1995).

Tc ng ca DA, bng cch kch hot cc recepter acid amin c bit m knh Na+, trn dng ion Ca2+ vo trong cc mng t bo thn kinh trung ng, lm cho mng t bo b kh cc (Viviani, 1992).

Cc hippocampus c th b hng nng, c th gy bnh mn tnh mt chc nng nh do cc h thng thn kinh b thoi ha do hm lng Ca2+ tng qu mc."269

c t sinh hc bin Tc dng c

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