title: 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.
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.
authors: Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt. Electronic address: yousefmokhtar@yahoo.com.
authors: Mokhtar I
authors: MI
authors: Yousef
authors: Pharmacology and Toxicology Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt.
authors: Hend M
authors: HM
authors: Hussien
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax / Q000737:chemistry*; D028321:Plant Preparations / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014508:Urea / Q000097:blood; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D028321:Plant Preparations; D012709:Serum Albumin; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D014508:Urea; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005982:Glutathione Transferase; D000251:Adenosine Triphosphatases; D005978:Glutathione; D002945:Cisplatin
keywords: Cisplatin; DNA damage; Ginseng; Interleukin 6; Tumor necrosis factor-α; Tumor suppressor P53