The protective effects of ursodeoxycholic acid and the selective cyclooxygenase-2 inhibitor celecoxib on liver damage in an experimental cholestasis model

Abstract

Aim: Cholestasis leads to liver cell death, fibrosis, cirrhosis, and eventually liver failure. Ursodeoxycholic acid (UDCA) is the only Food and Drug Administration-approved treatment for cholestatic disorders. Hepatic cyclooxygenase-2 (COX-2) expression increases in various chronic liver diseases caused either by viruses or toxins. The present study was conducted to investigate the effects of UDCA and the selective COX-2 inhibitor celecoxib on inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL). Methods: Fifty Sprague–Dawley rats that underwent common BDL for 21 days were assigned to one of five treatment groups (sham-operation, BDL, daily UDCA treatment following BDL, daily celecoxib treatment following BDL, and daily celecoxib and UDCA combination treatment following BDL). Serum and liver samples were collected after 21 days. Fibrosis, ductular proliferation, and portal inflammation were scored in liver samples. Liver function tests were evaluated. Results: In comparison with the control group, the BDL group showed hepatic damage as evidenced by elevation in serum biochemical and histological changes such as ductular reaction, fibrosis, and inflammation. These pathophysiological changes were attenuated by chronic UDCA and selective COX-2 inhibitor celecoxib supplementation. Conlusion: Our findings indicate that the addition of Celecoxib to UDCA reduces liver inflammation and fibrosis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The beneficial effects of chronic UDCA and Celecoxib supplementation may be associated with their potential cytoprotective, anti-oxidative and anti-inflammatory effects.