Oxidative changes in the liver, brain and lens of lipopolysaccharide-treated rats

Oxidative damage in various tissues of LPS-treated rats was studied using the following parameters: changes in reduced (GSH) and oxidized glutathione (GSSG) levels in liver, brain and lens; the activity of glutathione peroxidase (GSH-PX) in both liver and brain; the content of cytochrome P450 reductase in liver. Bacterial LPS was injected i.p. (at a dose of 4 mg/kg BW) 6 h before the animals were killed. One group of rats received N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) (given for 4 days in the drinking water at a concentration of 50 mM); another group received both L-NAME and LPS. In brain and lens no changes in GSH were observed after either LPS, L-NAME or both. In contrast, GSSG and the GSSG/GSH ratio was significantly higher after LPS. This effect was abolished in the brain by L-NAME treatment. The level of the activity of the antioxidative enzyme GSH-PX in brain was significantly higher after L-NAME in LPS-treated animals. Hepatic GSH-PX activity was enhanced after either LPS, L-NAME or treatment with both substances. Additionally, LPS diminished the level of cytochrome P450 reductase with this effect being largely prevented by L-NAME. The results suggest that GSH, as an endogenous antioxidant, may play a major role in combating toxicity of LPS.