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.
Sewerynek
E
E
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78240-7762, USA.
Abe
M
M
Chen
L
L
Ortíz
G G
GG
Reiter
R J
RJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides