Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

The present study aimed to clarify the effect of Copper oxide nanoparticles (CuO NPs) on hepatocellular carcinoma HepG2 cells in vitro and on normal rat liver in vivo. In addition, evaluation of the therapeutic efficacy of individual or combined doses of dehydro-epiandrosterone (DHEA) and quercetin in ameliorating some biochemical indices in liver of CuO NPs intoxicated-rats. CuO NPs (50nm) was administered at a dose of 100 mg/Kg for two weeks to rats followed by the fore-mentioned antioxidants for 3 weeks. In the present study, we highlighted the therapeutic effect of DHEA and/or quercetin against CuO NPs toxicity through monitoring the alteration of liver enzyme markers, antioxidant defense mechanism, necrosis, apoptosis, hepatic histopathological alterations, and DNA damage.The rats given CuO NPs only showed marked significant elevation in liver enzymes, alteration in oxidant-antioxidant balance and an elevation in the hepatic inflammatory marker; tumor necrosis factor-Ü (TNF-Ü). Additionally, over expression of both caspase-3 and Bcl2 associated X protein were detected. Whereas, B-cell lymphoma-2 was down regulated and DNA fragmentation was elevated. Moreover, histopathological examination of hepatic tissue reinforced the previous biochemical results.Treatment with either DHEA, quercetin alone or in combination ameliorated the deviated parameters against CuO NPs toxicity in rat with variable degrees.In conclusion, our findings suggest that the fore-mentioned treatments exert therapeutic effect in CuO NPs toxicity by diminishing oxidative stress, mRNA gene expression and hepatic tissues DNA damage

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