Effect of celecoxib, a selective cyclooxygenase-2 inhibitor on carbon tetrachloride intoxication in rats.
CCl(4) (0.5 ml/kg as CCl(4)) was orally administered to rats. Twelve hours after administration of CCl(4), 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 CCl(4) treatment did not change plasma ALT and AST and liver vitamin C levels 12 h after CCl(4) treatment, but 24 h after CCl(4) 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 CCl(4) in the second phase. Although the plasma levels of all ceramide species were significantly increased 24 h after CCl(4) intoxication, treatment with celecoxib significantly reduced the total ceramide concentration in plasma. These results indicated that celecoxib significantly ameliorated the toxicity of CCl(4) in the second phase.
Washino
Yukiko
Y
Department of Food Science and Nutrition, Nara Women's University, Japan.
Koga
Eriko
E
Kitamura
Yuko
Y
Kamikawa
Chiaki
C
Kobayashi
Keiko
K
Nakagawa
Tomoka
T
Nakazaki
Chihiro
C
Ichi
Ikuyo
I
Kojo
Shosuke
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000378:metabolism; D000068579:Celecoxib; D002518:Ceramides / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009336:Necrosis / Q000209:etiology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D002518:Ceramides; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068579:Celecoxib; D001205:Ascorbic Acid