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Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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Page 1: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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DOI : 10.4197/Sci.21-2.16

٣٩٥

���� ���� �� � ������� ������Cytoprotective ��

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Doxorubicin (DOX)� ��� ����� ������ �!"�� �#$ �������

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)!"23 �&#� / ������ $�&�� "�!�� ��&(LD) 53�&#�/ ��& .

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<��*���� ����"�� �=� <"�- ���&�� �-�� �-�� �!�"�� ����

Page 2: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

������ ��� �� ����� ٣٩٦

�� #�"���� $��&��"� DOX %�� . ������ :�� >'"�! ��/� "�

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#�=�� ��"/� %�"0�� $��&��� �� "�� . B� ��� ������ >'"�!

��"���C�D��� ��"� <"� ����� ������ �!"�� ��� �� E�����

�F�� �1Protective �!"%���� ;���7� &�"�� G"!=1 ���� �"���

DOX.

������

���� ����(Doxorubicin) (DOX) ��� ���� ��� ��� ����“Adriamycin”��� ��� ������ � ���� �� ���� ����� �� !�"� ��� � �#���� �$���)�"������ (���"%� &�' *+, &�� -� .� ./� 0121&

�����“Arcamone and Cowreker” �#���� &��3� �'��� � ����4 )cancer

chemotherapy(]�[ . ����+ �6��� �� �������� ���#� ���DOX7$� *+ ����� ��#�� �����4 �"������ �8���� � (Breast cancer) � 4��� ,

(Leukemia) � 6 ��� ,(Lymphooms)]�[ . 9�� � � ���DOX -�����

� ��� *�� :���3� &;� � �<�� :���� �'�"� � �� �'�"3� ��� �" / �� � ������ *+ =����]��[. 9�� ���� �#>DOX$��� ��� �$��� ������ �

��6�� ����� �� ���?� &;� � ,����� ��� �#�4��� &���"8� ���� �#����@���A �64 DOX������ ��'�� 7��"A ��� ����B ; ����� � ��� )free

radicals formation(]� ��[. .4C�� D�)0 (9�� �� DOX ��'�� E�" �����9������ � .3�:4� �4� ��� �� ��) Semiquinone free

radicals(]������[ .��� �� .�/��8� -��43� �� /"A � �� '

Page 3: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

���� ����� ����� ������� �����!Cytoprotective �"���� #���$%��� �" ... ٣٩٧

(oxidation reduction enzymes)]��[ ���� ��'�� E�" @� �'�43� �' *+

��43� �+(O•

2) �'��F�� ��4�� ,(H2O2)���� .�4��F�� ��' , (HO

•)

][. � "� &��"�#�� *+ 9�� .��6�DOX ����� = (Fe3+

) ��� �4�� (iron-doxorubicin complex) -��43� �$��6� � ����� *+ .�� ���� ,

�/��8�'��F�� ��4�� �F"� E�" . �H2O2. -���� ��'�� �� ���� 9�� ����� �'�" ��DOX��� :��� ������ �� �� ����� *+ �;/6�� ��

�4��H2O2,�;��� = ����6� ��> ���� Lipid Peroxidation (LPO)]��[

� /$��� �CG3� :��� ��A . 9�� @�� @�DOX ���#H��� � ����� &�'�� *+ ���� ����3� *+ �'�"�� ���I��� ��� �� :����4]��� [ ,

��4�� ]���� [ ,�4���]���[,�" �� .�]����[.

J"�4 ����� ���"�� � .���� .���� �/��� � ���� ,&����� ���"� K��� *+ L9�� 7$� *+ .���� ����+ &��� �#���� ����� @���3� EM��" ,L��9 3�

���� ���� ���"�� � .���� ����� �9��4��� (antibacterial)]� [ , -��9

�F� - (antiseptic)]��[ ,���� � ����6�� (antiviral)

]��[ . ���" ��� &����� N�9'�� 7$� *+ =��Wounds ��9������ ,Ulcers ��9��� ,Burns

����F��8�(inflammations)]����[ ,O�8 � .4Gribel and Pashinskii

]��[ Elawadan and El-Drieny

]��[&��P� -��� �� .���� Q�� .

������ ������� K�F� 9�� � � ���� ��ADOX��� �� ���� ���'�� �� ��Lethal Dose (LD) �� �� ��� ,(sub-lethal dose) (Sub-LD) ,

�� �� K<"(median lethal dose) (LD50), *+ .���� ����+ ��� K����� �F��� *��� ��� �� �'�"�� ���#H��� � ���� ��FO �� ���I��� � ����

�9�DOX�H6�� ��4 *+ .

Page 4: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

������ ��� �� ����� ٣٩٨

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������� R�; *+ &�����0S2��H+ � ����� (Albino mice) ��$� � "Mus

musculus (MF1)"�4��� � �F� ' , �9F+ U9� �� /4� � �F��' &� �I����� ������ ��/� ��� ,//��� ��� U� �� �� �'� ����� @����)VW ± V &' .(

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Page 5: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

���� ���� �� � ������� ������Cytoprotective����� � ������� � �� ... ٣٩٩

��9" ��6�� �9�� �9�� �9"/�� �9��� ��� �F��I� � �(vitamins) �" 3� L� �3�(amino acids) K��3� (fibers) N$ 3� ,(salts) .9#

� &������ ���9��� �� �� �+� ��� ��� = &���4�� �6�6�� ��� ����(tap water)�B�� .� . ���9�� -� � �F �BH� ��� :��'��� ��"�� � �B

*����� �"�� ��� ��� ' ��A :

) � (��3� �� ' �� )Y2n= (*� � ��A � �B ,� � �����8 � �����:

)� ( �� ' �����)Zn= (�"�� *"9����� K9'��� *9+ (i. p.) .���� *'��+ *�� .�� �.

)� ( �� �� �� ' )[Zn=( ��A � �B ,2 �"�� ���+ ��� ' /4���� -��� ���'� *"����� K'��� *+ �� ' .4 �6���

)4 mg/kg ,8 mg/kg ,15 mg/kg, 20 mg/kg ,25 mg/kg ,30

mg/kg (9�� � DOX�F����� � � .94 �F<�+ &�� ���� -� � 0\�4���� ��O�$ �� ��FO �� ���I��� .'�� ���� .

): ( �"�#�� �� ' ��)YSn = ( �9 �9��� *+ .���� ����+ ������ � ����� 9�� ��� �� �'��"�� ��� �� ���#H���DOX *"9����� K9'��� *+

*� � ��A � �B ,�� �� �� � =���� ���� .$� : )� ( �� ' �������)Yn=(.���� *'��+ *�� .�� � �"�� , .

)� ( �� ' DOX )\Sn=(���'� ����� �"�� , 4 mg/kg DOX =���� ���� -� � .

)� ( �� ' DOX .���� )\Sn=( �9��'� ����� �"�� ,4 mg/kg DOX .����� � �F��I� &� ,)5ml/kg( -�9 � &96�� ��� ��

=���� ����.

Page 6: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

������ ��� ��� !�"�� ٤٠٠

)� ( �� ' .����)Yn=( .�9���� � �F��I� &� ,)ml/kg 5 ( -�9 �=���� ���� .

��������� �� � Doxorubicin

�6C9�� ���9< � ������ /;�'�� ������ .�� ��� .<��� &� ��9���4� �9��4��; �9M; �9�� -�'� *"� �3� ������ �6C�� ��

(Doxorubicin hydrochloride) �4�9C 7�9�"A � "EBEWE Arzneimittel

Ges.m.b.h".

���� Honey

����� .�� &�����) ����� ���" � E�" ��Sidr 99� �9 �� K�9� �� “Ziziphus spina-christi”( *�� �� ���� � ��� .<� ,) *9��� .�9� (

���9"� ��� �� �� �� &������� K6� ,*��� .��" � E�" ��YS] .F�9� �<� ��<.

��� ����� ���� Measurement of Liver Function

� 4 ^�B ��� �� ��4�� KM�O ���� &�) �9�� -�9�/ �9��U/L (/��6�"��� " � �������AST /��6�"��� �"�P��ALT&��� .< *+ .

������ ������� ����� The Sick Textile

� -� .� �4� ��� ��"���� D�C� &� �9�F' �� DM��C�� ���� ���'�� C9�� �I�9< ���� �� �"���� ������� ��4�� E�"� ���94�� F��� DM��

��3�.

�������� ������ Statistical Analysis

*M�<�%� E �"���� &�����“Sigma stat V2” ��9"���� .��� �'��� � . �� ������� ��/3� *+ ��B�6�� �+�� � �� ' �� �� �� /"`� �� 4

Page 7: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

���� ���� �� � ������� ������Cytoprotective����� � ������� � �� ... ٤٠١

������ &������ &� �6��� �� = �' �� �������“Student's t-test” &���9�� , ������Z-test �� �� �� �� ' �� �� ��4C�� ���I��� �FO ���" *+ �"��� ��

����4 � � �B ,.���� = �����4���� �� �� �� �� ' �� �����4�����"�� *������ ���� .4C ��� EM� ± ���� �� H����(Mean ± Stander Error)

(M±SE) . �"��4�%� .��'�� E �"�� &�����(Microsoft Excel 2003) . �� �"���� &����.

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�� ��(lethal) VS &'� / &'4) .4C\( ��# �B$��� �� .4C�� � D�� ,�� ���'�� � 4 �����4���� & ����� ���� ��.

���)�(. ��� �� ��� ���� ���� �� DOX ������� ����� ������ ���� !��

"��#���)4, 8, 15, 20, 25, 30 mg/kg (��$ ��� �%#.

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Page 8: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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-�C�� �� ��B�� �� ��FO� 9��� �� �� �� ���M6��DOX �9 *"�9�� �9F"� �F����C" *+ &�� K��(weakness in general activities) �4���� ��/�� &��

(unbalanced movement) �;�9O �� ��4C9�� ���9I��� L9�� �FO = ��� ��) .�'0 .4C V( , ��C9�� ���9�+ ���9I��� �� C(hair loss)

(Alopecia)K���3� *�6��� U6�� ����� ��<�� � , � �9�� .����Red

urine ��'�� *+ �������� ,(skin ulceration) &96�� K"3� � � ��� K/"�� ,(nose & mouth bleeding) �99���(eye bleeding) , �99FO�� ^99��

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9��� �� �� �� �� ' ��DOX .����� -��I ��)Y . /&'4 ( � ) .4CV .( ������� �� ' �� *+ *�� � ��FO �I� @�� O�$ &� �� ' �� �

� -��I ����+ .����.

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��� �� ��� �� ��� ������ Red urine ���,�±

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Page 9: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

���� ��� ����� ������� �������Cytoprotective������� ����!"��� �� ... ٤٠٣

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*+,�� ������ � ������ ���-�� Morphological Changes �����DOX ���� ����� �����DOX

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Page 10: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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Page 11: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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Page 14: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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Page 16: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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Page 18: Cytoprotective - kaukau.edu.sa/Files/320/Researches/53965_24482.pdf200 X C V د ج 400 * 400 X ـه 400 و ... (Mostafa et al.) ˘ ;H .DOX (fatty infiltration) ٤١٣ ... ˚ Cytoprotective

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The Possibility of Using Honey as Cytoprotective Against

Pathological Effect of Doxorubicin;

Morphological Changes, Toxilogical Symptoms,

Histological Structure and Functions of Mice Liver

M. A. Ganash, M. I. Mujallid and A.A. Al-Robai

Department of Biological Science, Faculty of Science,

King AbdulAziz University

P. O. Box 80003 Jeddah 21589, Saudi Arabia

Abstract. Doxorubicin (DOX) is one of the most important cytotoxic

drugs in cancer chemotherapy. However, it causes pathological effects

on many organs. The aim of the present study was to investigate the

possible protective effect of honey. Albino mice of MF1 (mus

musculus) strain weighting 37±3 g were obtained from king Fahd

medical research center. Mice body and liver weight , morphological

and behavior changes as well as liver function and pathological effects

on liver were recorded. Administration of DOX to mice induced

weakness in general activities of animals with several morphological

changes during experiment such as bleeding, ulcerations, dermatitis,

alopecia, abnormal limbs, and bosselation. Toxicity study of DOX

showed that the LD50 and LD were 20 and 30 mg/kg of DOX,

respectively. The results of honey administration to mice reduce

pathological symptoms caused DOX as indicates by body weights and

liver, which were higher than that of DOX only. In addition, daily

administration of honey for seven weeks decreased these

histopathological changes, the structure of liver and hepatocytes

appearance was more or less similar to control group as well its

function. The present results indicate that honey may play an

important role as Cytoprotective and pave the way for further studies

on the possible use of honey.