Antifibrotic potential of a selective COX-2 inhibitor (celecoxib) on liver fibrosis in rats

Hepatic stellate cells (HSCs) play a critical role in the fibrogenesis of the liver, so they are the target cells of antifibrotic therapy. Activated HSCs, but not quiescent HSCs, express cyclooxygenase-2 (COX-2). The present study was designed to investigate the possible prophylactic and therapeutic effects of a selective COX-2 inhibitor (celecoxib) on liver fibrosis induced by thioacetamide (TAA) in rats. Forty-two male albino rats were divided into five groups: group I, negative control; group II, model of fibrosis; group III, preventive model before induction of fibrosis where celecoxib was given for 4 weeks before TAA; group IV, preventive model at the time of induction of fibrosis where celecoxib was given concomitantly with TAA for 6 weeks; group V, therapeutic model treated after induction of fibrosis. Liver function tests, serum TGF-β1 (ELISA), and histopathological examination of liver sections were performed. Both Metavir and Ishak fibrosis scoring systems were used for the evaluation of fibrosis. Groups III, IV, and V showed significant amelioration of liver function tests and a decrease in serum TGF-β1 as compared to the fibrosis model group (II). Histopathological examination showed the mildest degree of fibrosis in group III. Celecoxib had a hepatoprotective and therapeutic effect against liver damage produced by TAA but with different degrees. The highest efficacy of celecoxib was in the preventive group (III) before time of induction of liver fibrosis, followed by the therapeutic group (V) and then the preventive group (IV) at time of induction of liver fibrosis.