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DOI : 10.4197/Sci.21-2.16
٣٩٥
���� ���� �� � ������� ������Cytoprotective ��
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Doxorubicin (DOX)� ��� ����� ������ �!"�� �#$ �������
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�F�� �1Protective �!"%���� ;���7� &�"�� G"!=1 ���� �"���
DOX.
������
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�����“Arcamone and Cowreker” �#���� &��3� �'��� � ����4 )cancer
chemotherapy(]�[ . ����+ �6��� �� �������� ���#� ���DOX7$� *+ ����� ��#�� �����4 �"������ �8���� � (Breast cancer) � 4��� ,
(Leukemia) � 6 ��� ,(Lymphooms)]�[ . 9�� � � ���DOX -�����
� ��� *�� :���3� &;� � �<�� :���� �'�"� � �� �'�"3� ��� �" / �� � ������ *+ =����]��[. 9�� ���� �#>DOX$��� ��� �$��� ������ �
��6�� ����� �� ���?� &;� � ,����� ��� �#�4��� &���"8� ���� �#����@���A �64 DOX������ ��'�� 7��"A ��� ����B ; ����� � ��� )free
radicals formation(]� ��[. .4C�� D�)0 (9�� �� DOX ��'�� E�" �����9������ � .3�:4� �4� ��� �� ��) Semiquinone free
radicals(]������[ .��� �� .�/��8� -��43� �� /"A � �� '
���� ����� ����� ������� �����!Cytoprotective �"���� #���$%��� �" ... 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$� *+ .���� ����+ &��� �#���� ����� @���3� EM��" ,L��9 3�
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]��[ . ���" ��� &����� N�9'�� 7$� *+ =��Wounds ��9������ ,Ulcers ��9��� ,Burns
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]��[ 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 *+ .
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�������� �� ��� Experimental Animals
������� R�; *+ &�����0S2��H+ � ����� (Albino mice) ��$� � "Mus
musculus (MF1)"�4��� � �F� ' , �9F+ U9� �� /4� � �F��' &� �I����� ������ ��/� ��� ,//��� ��� U� �� �� �'� ����� @����)VW ± V &' .(
Unpaired
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Reactive oxygen species
(O2●-, OH
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Reduce
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Free radical
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OXIDATIVE
DAMAGE AND
CELL INJURY
Fe
Oxidation
In normal
conditions
Antioxid
Iron-Doxorubicin
complex
DNA
Damage
�������� �� � �������Oxidation-Reduction
Enzymes
���� ���� �� � ������� ������Cytoprotective����� � ������� � �� ... ٣٩٩
��9" ��6�� �9�� �9�� �9"/�� �9��� ��� �F��I� � �(vitamins) �" 3� L� �3�(amino acids) K��3� (fibers) N$ 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�� ��� ��
=���� ����.
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)� ( �� ' .����)Yn=( .�9���� � �F��I� &� ,)ml/kg 5 ( -�9 �=���� ���� .
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�6C9�� ���9< � ������ /;�'�� ������ .�� ��� .<��� &� ��9���4� �9��4��; �9M; �9�� -�'� *"� �3� ������ �6C�� ��
(Doxorubicin hydrochloride) �4�9C 7�9�"A � "EBEWE Arzneimittel
Ges.m.b.h".
���� Honey
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���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
���� ���� �� � ������� ������Cytoprotective����� � ������� � �� ... ٤٠١
������ &������ &� �6��� �� = �' �� �������“Student's t-test” &���9�� , ������Z-test �� �� �� �� ' �� �� ��4C�� ���I��� �FO ���" *+ �"��� ��
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(M±SE) . �"��4�%� .��'�� E �"�� &�����(Microsoft Excel 2003) . �� �"���� &����.
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�� ��(lethal) VS &'� / &'4) .4C\( ��# �B$��� �� .4C�� � D�� ,�� ���'�� � 4 �����4���� & ����� ���� ��.
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urine ��'�� *+ �������� ,(skin ulceration) &96�� K"3� � � ��� K/"�� ,(nose & mouth bleeding) �99���(eye bleeding) , �99FO�� ^99��
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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.