Thesis (M.Sc.) - Mansoura University - Faculty of Veterinary Medicine - Department of Biochemistry and Chemistry of Nutrition

Cisplatin (CP) is an effective chemotherapy that is used widely in treatment of malignant tumors. However due to its toxic side effects both CP dose and duration are limited. Nephrotoxicity is one of the major side effects caused by CP. Several strategies and agents were studied in attempt to protect against CP harmful effect on kidney but not proved useful and safe for clinical use. Dietary flaxseed oil (FXO) is considered the richest plant source of omega 3 (PUSFA) which is proven for its anti-oxidant and anti- inflammatory properties. The protective effect of FXO on CP induced nephrotoxic and other deleterious effects were investigated. Rats were pre-fed experimental diet for 10 days and then injected with a single dose of CP in two different concentrations (3 mg/kg and 5 mg/kg body weight) intra-peritoneally while still on diet. Serum chemistry and oxidative stress parameters were analyzed as well as immunohistochemistry of TNF-Ü and NF-KB also Rt.PCR analysis of IL-6 AND IL-1b of kidney tissue. The results revealed that CP nephrotoxicity significantly increased serum creatinine levels and urea levels. Also CP significantly decreased antioxidant defense mechanism (superoxide dismutase SOD, glutathione peroxidase GPx) and increased lipid peroxidation level (malondialdhyde MDA) with elevated TNF-Ü and NF-KB levels in addition to elevation in both IL-6 and IL-1b expression. In contrast FXO increased antioxidant enzymes (SOD, GPx) and reduced lipid peroxidation MDA and serum creatinine, urea levels, TNF-Ü, NF-KB, IL-6 and IL-1b expression .Dietary FXO supplementation ameliorated CP induced specific metabolic alterations and oxidative damage due to its intrinsic biochemical antioxidant properties

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