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Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: Protective effect of ginseng

Author:
Yousef, Mokhtar I., Hussien, Hend M.
Source:
Food and chemical toxicology 2015 v.78 pp. 17-25
ISSN:
0278-6915
Subject:
DNA, DNA damage, DNA fragmentation, DNA repair, Panax, adenosinetriphosphatase, antioxidants, apoptosis, blood serum, cisplatin, creatinine, drug therapy, enzyme activity, gene expression, interleukin-6, kidneys, microscopy, necrosis, neoplasms, nephrotoxicity, nitric oxide, oxidative stress, protective effect, rats, superoxide dismutase, thiobarbituric acid-reactive substances, toxicology, tumor necrosis factor-alpha, tumor suppressor protein p53, urea, xanthine oxidase
Abstract:
Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.
Agid:
5419607