Effect of celecoxib on experimental liver fibrosis in rat.

BACKGROUND/AIM: Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes prostaglandin synthesis, has been implicated in a number of hepatic stellate cell (HSC) functions. In the current study, we assessed the in vivo effect of celecoxib, a COX-2-selective inhibitor, in experimental liver fibrosis in rats.

METHODS

Male Sprague-Dawley rats received experimental treatments for 5 weeks. Serum alanine transminase at the time of sacrifice was measured. Quantitative assessment of liver fibrosis was performed by computerized morphometry. Expression of COX-2, alpha smooth muscle actin and connective tissue growth factor (CTGF) was evaluated by immunohistochemistry. Real-time quantitative PCR was used to determine the expression of genes associated with fibrogenesis and extracellular matrix degradation.

RESULTS

Liver fibrosis was significantly worse in rats that received both carbon tetrachloride (CCl4) and celecoxib, compared with rats that received CCl4 and gavage of water (P = 0.037). There was also more HSC activation, and upregulation of collagen alpha1(I), heat-shock protein 47, alphaB crystallin, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of MMP (TIMP)-2. The expression of TIMP-1 and CTGF was not significantly different between the two groups. The pro-fibrogenic effect of celecoxib in toxin-induced liver fibrosis in rats was further confirmed in thioacetamide model of liver injury.

CONCLUSIONS

Celecoxib potentiates experimental liver fibrosis; further studies are warranted to investigate the potential pro-fibrogenic effect of celecoxib in other animal models of liver fibrosis and in patients with chronic hepatitis.