Effect of nimesulide against indomethacin- induced oxidative liver damage in rats

Abstract

Indomethacin is used in the treatment of ankylosing spondylitis, osteoarthritis, tendinitis, and other inflammations. However, it has been reported indomethacin has nephrotoxic, gastrotoxic, and hep-atotoxic effects. The aim of this study is to investigate the effect of nimesulide on indomethacin-induced liver damage in rats biochemically and histopathologically. Experimental animals (21 rats) were divided into 3 groups: the healthy (HG) group receiving distilled water as a solvent, the 25 mg/kg indomethacin administered (IDO) group, and the 50 mg/kg nimesulide + 25 mg/kg indomethacin administered (NIDO) group. Malondialdehyde (MDA), total glutathione (GSH) levels and cyclooxygenase-1 (COX-1), cyclo-oxygenase (COX-2) enzyme activities were determined from liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured in serum. The data obtained in the IDO group were compared with the data obtained from the NIDO and MDA and decreased tGSH levels with indomethacin HG groups. Increased application in liver tissue approached the HG group with nimesulide application, and the difference was found to be insignificant. Nimesulide prevented the decrease in COX -1 and COX-2 levels observed with indomethacin administration. Again, the increase in ALT and AST levels, which increased with indomethacin administration, was prevented by nimesulide. As a result of the histopathological evaluation, it was observed that nimesulide reduced the damage caused by indometha-cin. Nimesulide at 50 mg/kg prevented oxidative liver damage induced with indomethacin at 25 mg/kg. Our results suggest that nimesulide may be useful in the treatment of hepatotoxicity and COX-1 inhibi-tion side effects without suppressing analgesic and anti-inflammatory activity due to indomethacin use