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Alleviation of hepatic injury by chrysin in cisplatin administered rats: Probable role of oxidative and inflammatory markers
Institution:1. Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan;2. Department of Geology, University of Peshawar, Peshawar, Pakistan;3. HEJ Research Institute, Institute of Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan;4. Department of Pharmacy, Abdul Wali Khan University of Mardan, Mardan, Pakistan;5. Department of Pharmacy, University of Peshawar, Peshawar, Pakistan;6. Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy;7. Department of Pharmacy, University of Naples, Federico II, Naples, Italy
Abstract:BackgroundCisplatin is an effective and extensively used chemotherapeutic agent to treat range of malignancies, but its therapeutic use is limited because of dose-dependent nephrotoxicity and hepatotoxicity. Several published reports advocate that supplementation with antioxidant can influence cisplatin induced hepatic damage.MethodIn the present study the Wistar rats were subjected to concurrent prophylactic oral treatment of chrysin (25 and 50 mg/kg b.wt.) against the hepatotoxicity induced by intraperitoneal administration of cisplatin (7.5 mg/kg b.wt.). Efficacy of chrysin against the hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes and expression levels of molecular markers of inflammation.ResultsChrysin ameliorated cisplatin-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, superoxide dismutase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated expression of COX-2, iNOS and levels of NFκB and TNF-α, and hepatic tissue damage which were induced by cisplatin. Histological findings further supported the protective effects of chrysin against cisplatin-induced hepatic damage.ConclusionThe results of the present study demonstrate that oxidative stress and inflammation are closely associated with cisplatin-induced toxicity and chrysin shows the protective efficacy against cisplatin-induced hepatotoxicity possibly via attenuating the oxidative stress and inflammatory response.
Keywords:Cisplatin  Inflammation  Oxidative stress  Hepatotoxicity
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