Protective Effect of COX and NOS Inhibitors on LPS Induced Oxidative Stress in Rat

Abstract

Background: LPS, a component of the cell wall of gram-negative bacteria, is one of the most potent bacterial products in the induction of host inflammatory responses and tissue injury and was used in this study to mimic infections. Purpose: The major goal of this study was to examine the ability of indomethacin, celecoxib, N G -nitro-L-arginine methyl ester (L-NAME) to protect the brain from oxidative stress by lipopolysaccharide . Methods: LPS was administered intraperitoneally at a dose 4 mg/kg to adult SD rats . Suspensions of celecoxib, indomethacin and L-NAME were administered orally at a dose of 76 mg, 2 mg and 30 mg per kg body weight after 1 hr of LPS treatment respectively. The animals were sacrificed 24 hrs after LPS injection. NOx and MPO activity was estimated in the brain homogenates. Results: LPS resulted in elevation of the level of Malondialdehyde (MDA, index of lipid per oxidation) and reduction of glutathione (GSH) in all the brain regions. Levels of nitrite/nitrate (NOx), a marker of reactive nitrogen species (RNS), was also found elevated in all the brain regions whereas myeloperoxidase (MPO), a heme-containing enzyme, was significantly increased only in cerebral cortex, hippocampus, thalamus and medulla. Both COX and NOS inhibitors ameliorated the oxidative stress induced by LPS injection by reducing levels of MDA, restoring GSH content and normalizing the NOx and MPO levels in the brain. Conclusion: The COX and NOS inhibitors regulate the increased free radical generation during infections and LPS-induced oxidative stress. doi: 10.5214/ans.0972.7531.2008.150102 Competing interests: None. Source of Funding: ICMR Received Date: 10 Jan 2008 Revised Date: 22 Jan 2008 Accepted Date: 30 Jan 2008