The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome‐encapsulated superoxide dismutase (L‐SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO(3)) to male F344 rats were investigated by measuring 8‐hydroxydeoxyguanosine (8‐OH‐dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre‐ and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8‐OH‐dG, LPO levels and RKW caused by 80 mg/kg KBrO(3) i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8‐OH‐dG, LPO levels and RKW after a 20 mg/kg KBrO(3) i.p. treatment, which itself caused no change. Administration of KBrO(3) itself reduced renal non‐protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO(3) lowered the non‐protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO(3) were also observed for pre‐ and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre‐ and posttreatment with 18,000 U/kg L‐SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO(3).