The anti-inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct-ligated rats
Publication in refereed journal


摘要Background/Aims: Celecoxib was used in the treatment of inflammation in patients with cirrhosis. However, data on the progression of liver fibrosis after treatment by celecoxib are not available. This study aims to elucidate the effects of celecoxib on cholestatic liver fibrosis in rats. Methods: Rats underwent bile duct ligation (BDL) for 1 or 2 weeks to induce hepatic fibrosis. Celecoxib was introduced on day 1 after operation. The effects of celecoxib were assessed by comparison of the severity of hepatic fibrosis. Results: Infiltration of inflammatory cells and proliferation of bile ducts was seen after 1 week of BDL and fibrosis was induced after 2 weeks. Reduced alanine aminotransferase (ALT) levels and blunted expression of inflammatory factors [tumour necrosis factor-α, interleukin (IL)-1β and IL-6] were seen in the liver of BDL-treated rats that received celecoxib at week 1. Although celecoxib was sufficient in suppressing the cyclo-oxygenase (COX)-2 expression in the control organ (kidney), it failed to suppress the enhanced hepatic COX-2 expression. At week 2, celecoxib did not alter the ALT level, the severity of fibrosis and hepatic collagen contents. This was associated with unchanged α-smooth muscle actin protein expression and tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expressions in the liver. Celecoxib had no effect on the BDL-dependent increase in bilirubin levels at any time point. Conclusions: The present study provides morphological and molecular biological evidences for the role of celecoxib in cholestatic liver fibrosis. Celecoxib protects against hepatic inflammation in the early stage of BDL rats, but does not have an effect on liver fibrosis. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard.
著者Yu J., Hui A.Y., Chu E.S.H., Go M.Y.Y., Cheung K.F., Wu C.W., Chan H.L.Y., Sung J.J.Y.
期刊名稱Liver International
出版社Blackwell Publishing Inc.
出版地United Kingdom
頁次25 - 36
關鍵詞Bile duct ligation, Celecoxib, HSC-T6, Liver fibrosis

上次更新時間 2020-12-10 於 00:22