Nimesulide affects antioxidant status during acute lung inflammation in rats

Antiradical activity of nimesulide, a commonly used COX-2 specific inhibitor, was estimated in vitro by 1, 1 diphenyl-2-picrylhydrazyl (DPPH) assay, nitroblue tetrazolium reduction assay and lipid peroxidation assay, respectively. The biochemistry of antioxidant functions of nimesulide was also investigated under control and inflammatory conditions, caused by intratracheal instillation of lipopolysaccharide (LPS). Pro-inflammatory conditions generally end up in oxidative insults, which have been suggested to be the cause of multiple organ failure in inflammation. A primary defense, constituted of antioxidant enzymes, against this oxidative damage has evolved in the body. In this study, male Wistar rats were orally administered with nimesulide (9 mg/kg/twice daily for 1 week), followed by intratracheal instillation with 2 microg of LPS and after 18 hr, antioxidant defense system and lipid peroxidation were measured in liver, lungs and kidneys. Nimesulide pretreatment was found to protect the tissue from enhanced levels of lipid peroxidation, and also stimulated the levels of glutathione-S-transferase (GST) in liver and glutathione reductase in kidneys. Surprisingly, nimesulide oral feeding also significantly suppressed superoxide dismutase (SOD) activity in all the three organs. Although, in our study, nimesulide proved to be an inducer of GST (a marker for chemoprevention) and a scavenger of superoxide anions at higher concentrations (> 250 microM), but the relevance of suppression of SOD enzyme activity, which may contribute to the drug's toxic effects cannot be ignored. The work suggests that further long term studies are needed to confirm nimesulide as a safe drug.