Celecoxib ameliorates liver cirrhosis via reducing inflammation and oxidative stress along spleen-liver axis in rats.

Abstract Background & aims Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver. Materials and methods Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups. Results Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O2− were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p  Conclusion Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.