Effect of selective cyclooxygenase‐2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts

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Abstract
Aim:  Cholestasis triggers fibrogenesis in the liver. Hepatic cyclooxygenase‐2 (COX‐2) expression increases in various chronic liver diseases caused either by viruses or toxins. We hypothesized that selective COX‐2 inhibitor meloxicam could suppress inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL).Methods:  Forty‐three Sprague–Dawley rats were assigned to one of four treatment groups (sham‐operation, BDL, daily meloxicam injections following BDL, and daily meloxicam injection without BDL). Liver histopathology was analyzed with hematoxylin–eosin and Masson's trichrome staining. The expression of α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1), and COX‐2 were measured with immunohistochemical staining. The levels of COX‐2, TGF‐β1, and matrix metalloproteinase‐9 (MMP‐9) production were measured with the Western blot method and an enzyme immunoassay.Results:  Meloxicam treatment attenuated the expression of α‐SMA, TGF‐β1, and COX‐2 in rats that were treated with BDL for 3 weeks. This was associated with a marked reduction in collagen accumulation and histological improvement. In addition, meloxicam treatment was found to downregulate the levels of hepatic COX‐2, TGF‐β1, and MMP‐9 production.Conclusion:  Cholestasis in BDL rats induces hepatic COX‐2 expression. Selective COX‐2 inhibitor meloxicam reduces BDL‐induced hepatic fibrosis, and this is associated with reduced hepatic TGF‐β1 expression as well as decreased cyclooxygenase activity in the liver.

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