Nimesulide inhibits lipopolysaccharide-induced production of superoxide anions and nitric oxide and iNOS expression in alveolar macrophages

• Published in: Life sciences (1973) 2006-03, Vol.78 (15), p.1662-1669
• Main Authors: Khanduja, Krishan Lal, Sohi, Kiranjit Kaur, Pathak, Chander Mohan, Kaushik, Gaurav
• Format: Article
• Language: English
• Subjects: Alveolar macrophages; Animals; Antioxidants - metabolism; Blotting, Western; Bronchoalveolar Lavage Fluid - cytology; Free Radical Scavengers - pharmacology; Free Radicals - metabolism; iNOS; Instillation, Drug; Intubation, Intratracheal; Lipopolysaccharides - toxicity; LPS; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - enzymology; Macrophages, Alveolar - metabolism; Male; Nimesulide; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - biosynthesis; Rats; Rats, Wistar; Sulfonamides - pharmacology; Superoxide; Superoxides - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.07.033

The study was designed to investigate the effect of nimesulide on lipopolysaccharide (LPS)-induced proinflammatory oxidants production by rat alveolar macrophages (AMs). Effects of LPS and nimesulide on antioxidant defense and the expression of inducible nitric oxide synthase (iNOS) were also studied. It was found that nimesulide could scavenge superoxide anions (O 2 − ), nitric oxide (NO ) and total oxidant burden induced by LPS in AMs in vitro. Approximately 850 nmoles of nimesulide had activity equivalent to one IU of superoxide dismutase (SOD). Further, to confirm the in vitro observation, Male Wistar rats were orally administered with nimesulide (9 mg/kg b. wt. twice daily) for one week followed by intratracheal instillation of 2 μg LPS to stimulate lung inflammation. AMs from bronchoalveolar lavage fluid were collected 18 h after instillation of LPS. Nimesulide pretreatment could inhibit O 2 − , NO and lipid peroxidation in AMs. Nimesulide also suppressed LPS-induced iNOS expression in AMs in vivo and in vitro. Nimesulide could also normalize LPS-induced changes in the levels of superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in AMs. Inhibition in production of oxidants in LPS-challenged AMs by nimesulide could be one of the pathways for its anti-inflammatory action.