Effect of Celecoxib, a Selective Cyclooxygenase-2 Inhibitor on Carbon Tetrachloride Intoxication in Rats

• Published in: Biological & Pharmaceutical Bulletin 2010/04/01, Vol.33(4), pp.707-709
• Main Authors: Washino, Yukiko, Koga, Eriko, Kitamura, Yuko, Kamikawa, Chiaki, Kobayashi, Keiko, Nakagawa, Tomoka, Nakazaki, Chihiro, Ichi, Ikuyo, Kojo, Shosuke
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; ascorbic acid; Ascorbic Acid - metabolism; Aspartate Aminotransferases - blood; carbon tetrachloride; Carbon Tetrachloride Poisoning - drug therapy; Carbon Tetrachloride Poisoning - metabolism; Celecoxib; ceramide; Ceramides - blood; Chemical and Drug Induced Liver Injury - complications; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Liver - drug effects; Liver - metabolism; Male; Necrosis - etiology; Necrosis - prevention & control; oxidative stress; Oxidative Stress - drug effects; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Rats; Rats, Wistar; Sulfonamides - pharmacology; Sulfonamides - therapeutic use
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.33.707

CCl4 (0.5 ml/kg as CCl4) was orally administered to rats. Twelve hours after administration of CCl4, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, indicators of liver necrosis, were significantly higher than those in the control group showing that active liver necrosis took place. At the same time the level of liver vitamin C was decreased significantly compared to that in the control group. Oral administration of 100 mg/kg each of celecoxib 3 and 8 h after CCl4 treatment did not change plasma ALT and AST and liver vitamin C levels 12 h after CCl4 treatment, but 24 h after CCl4 treatment, significantly decreased plasma ALT and AST levels and elevated liver vitamin C level. These finding suggested that celecoxib effectively ameliorated the necrotic action and the oxidative stress induced by CCl4 in the second phase. Although the plasma levels of all ceramide species were significantly increased 24 h after CCl4 intoxication, treatment with celecoxib significantly reduced the total ceramide concentration in plasma. These results indicated that celecoxib significantly ameliorated the toxicity of CCl4 in the second phase.