Celecoxib, a selective cyclooxygenase-2 inhibitor, lowers plasma cholesterol and attenuates hepatic lipid peroxidation during carbon-tetrachloride–associated hepatotoxicity in rats

Abstract

Cyclooxygenase-2 (COX-2) expression and prostaglandin production are suggested to play important, complex roles in the pathogenesis of various liver diseases. Studies on the effects of COX-2 inhibitors on the progression of liver fibrosis present controversial results, and the proposed therapeutic potential of these agents in chronic liver disease is predicated largely on their effectiveness in modulating hepatic stellate cell activation in vitro. This study investigated the modulatory effect of celecoxib, a selective COX-2 inhibitor, in CCl₄-mediated hepatotoxicity in rats. Thirty Wistar albino rats, weighing 120–180 g, were assigned into five groups of 6 rats/group. Groups 1 and 2 received saline (10 mL/kg) and CCl₄ (80 mg/kg), respectively. Group 3 was given celecoxib (5.7 mg/kg), whereas groups 4 and 5 were pretreated with 2.9 and 5.7 mg/kg/day of celecoxib, respectively, 1 hour before CCl₄ treatment. Plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities increased significantly by 118.5, 150.0, and 51.3%, respectively, with an accompanying decrease (P < 0.05) in total protein and albumin after CCl₄ treatment. Hepatotoxicity was associated with a significant increase in plasma cholesterol, hepatic lipid peroxidation (LPO), and severe hepatic necrosis with marked fatty and cellular (i.e., mononuclear cells) infiltration. Although celecoxib neither reduced CCl₄-induced increases in marker enzymes of hepatotoxicity nor significantly attenuated hepatic necrosis, it, however, was effective in reducing elevated cholesterol by 16.5 and 20.8% and LPO by 12.9 and 35.5% at 2.9 and 5.7 mg/kg, respectively. Data suggest that COX-2 inhibitors may be effective in controlling hypercholesterolemia and peroxidative changes associated with liver injury.

Keywords::

• Hepatotoxicity
• carbon tetrachloride
• cyclooxygenase-2 inhibition
• celecoxib

Acknowledgments

The authors acknowledge the support of Prof. E.O. Ogunyemi, the Head of the Department of Chemical Pathology and Immunology of the Olabisi Onabanjo University Teaching Hospital, at the time of this study. The assistance of Ms. N.T. Oresanya of the Department of Pharmacology is also gratefully acknowledged.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.