Histopathological Effects of Doxorubicin and Nanoparticle Zinc oxide on DNA damage and Hepatotoxicity induced by CCl4 in rats

Document Type : Scientific and Research

Authors

1 Molecular Biology department, Genetic Engineering and Biotechnology Institute (GEBRI), Sadat City University

2 Biochemistry,Toxicology and Feed Deficiency department. Animal Health Research Institute

Abstract

Nanoparticles are important scientific tools that have been recruited in various biotechnological, pharmacological applications. Zinc oxide nanoparticles are used considerably for its catalytic, electrical, optoelectronic and photochemical properties. Quinine- containing anthracycline antibiotic doxorubicin (DXR) has been used for the treatment of a wide variety of cancers, despite of its high antitumor efficacy DXR use in chemotherapy has been largely limited due to its cardiac, renal and hepatic toxicity. The present study has been carried out to evaluated the effect of Doxorubicin and ZnO NP when use together and separately against the CCl4 induced hepatotoxicity in the rats. The damage of the liver caused by CCl4 and Doxorubicin was evident by DNA gel electrophoresis and histopathology. In the present study, Fourty eight white Albino rats (Sprague Dawley strain) were divided into 8 equal groups of 6 rats each for 28 successive days. Group one was kept as a control –ve, second and third groups were injected intraperitonily with DOX(6 mg/kgb.wt) and nZnO(5 mg/kgb.wt) respectively for 3 successive days. While fourth group was injected intraperitonily nZnO followed by DOX for the same period. On the other hand, other four groups were injected subcutaneously with CCL4 50% (0.1 ml/100g.b.wt.twice/week for two weeks )to induce DNA damge and Hepatotoxicity. One of this groups was kept as a control +ve (CCL4 groups).Second and third groups were injected intraperitonily with DOX (6 mg/kgb.wt) and nZnO (5 mg/kgb.wt) respectively for the same period.While fourth group was injected intraperitonily nZnO followed by DOX for the same period. At the end of experimental period the liver and spleen tissue were used for histopathological assessment.and illustrate DNA damage in hepatocytes. Vacuolar degeneration associated with proliferation of fiberous connective tissue surrounding the hepatic cells with dilated hepatic artery was observed in the group which received CCl4 and doxorubicin. Examination of the spleen showed severe depletion in lymphoid elements in both white and red pulb especially in the center of lymphoid follicles. Subcutaneous injection of CCl4 induce DNA fragmentation and intraperitoneal injection of doxorubicin showed DNA fragmentation while rats injected Doxorubicin and ZnO NP showed less DNA fragmentation . The ZnO NP treated animals showed reversal of toxic effects in the liver cells.
 Thus, it can be concluded that the reduce DNA damge and improved histology of the liver and spleen as seen in the histopathological observation on animals treated with ZNO NP as compared to that seen in animals administered only CCl4 or only Doxorubicin indicated possibility of the ZnO NP being able to induce accelerated regeneration of the liver and spleen 

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