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Document Type |
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Thesis |
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Document Title |
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Enhancement of the activity of doxorubicin by a natural product resveratrol (pharmacological and toxicological study) تعزيز نشاط عقار الدكسوروبيسين بواسطة المنتج الطبيعي الريسفيراترول |
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Subject |
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Faculty of Medicine > MEDICAL PHARMACOLOGY |
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Document Language |
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Arabic |
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Abstract |
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Doxorubicin (DOX), an anthracycline antibiotic, is one of the most effective anticancer drug used in the treatment of variety of cancers. Its use is limited by its cardiotoxicity. The present study was designed to assess the role of the natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and its protective effect against DOX-induced cardiotoxicity in rats. For this study, rat and Ehrlich ascites carcinoma bearing mice were used. Percent survival of tumor bearing mice was used for determination of the cytotoxic activity of DOX in presence and absence of RSVL. Uptake and cell cycle effect of DOX in tumor cells in the presence of RSVL were also determined. Serum total lactate dehydrogenase (LDH), total creatine phosphokinase activities (CPK), total antioxidant activity (TAC). Malondialdehyde, glutathione and histopatholgical examination of heart tissues after DOX and/or RSVL therapy were also investigated. DOX at a dose level of 15 mg/kg increased the mean survival time of tumor bearing mice to 21 days compared with 15 days for tumor-bearing control mice. Administration of RSVL at a dose level of 10 mg/kg simultaneously with DOX increased the mean survival time to 30 days with 70% survival of the tumor-bearing animals. RSVL increased the intracellular level of DOX and there was a strong correlation between the increased cellular level of DOX and its cytotoxic activity. Moreover, RSVL treatment showed a 4.8 fold inhibition in proliferation index of cells treated with DOX. Also, DOX treatment caused a significant increase in serum cardiac enzymes LDH and CPK activities and cardiac tissue malondialdhyde . Moreover, there was a significant decrease in reduced glutathione level. Rats histopathological examination of rat heart tissue after a single dose of DOX (20 mg/kg) showed myocytolysis with congestion of blood vessels, Mitochondria showed either vacuolization or complete loss of the cristae. Simultaneous treatment with RSVL, fragmentation of the muscle fiber revealed normal mitochondria and muscle fiber. Simultaneous treatment of rats with DOX and RSVL (10mg/kg,i.p.) significantly reduced the activity of LDH and CPK, and malondialdhyde production in heart tissues . Administration of RSVL increased total antioxidant capacity was. This study suggests that RSVL would increase the cytotoxic activity of DOX and protect against its cardiotoxicity. |
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Supervisor |
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dr. . Abdel-Moneim M. Osman. |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1435 AH
2014 AD |
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Co-Supervisor |
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Dr. Sameer E. Al-Harthi. |
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Added Date |
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Tuesday, May 27, 2014 |
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Researchers
| عهود محمد العرابي | AlOraabi, Ohoud Mohammed | Researcher | Master | |
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