Limited potential of resolvin D1 in treatment of cholestatic liver fibrosis

Background: Several studies suggest a role for EPA- and DHA-derived pro-resolving mediators like resolvins in reversing metabolic and inflammatory disturbances seen in various chronic diseases. Here, we investigated the effects of resolvin D1 (RvD1) on bile duct ligation (BDL)-induced cholestatic liver injury. Methods: Mice were treated daily with RvD1 or 0.1% ethanol (control) from the day of BDL until the final observation time points. Blood and liver tissue were collected 2, 5 and 14 days after BDL for different analyses. Results: RvD1 treatment of mice had no impact on the extent of cholestatic liver injury upon BDL, neither in the acute phase nor in the progressive state of liver fibrosis. Although RvD1 treatment resulted in a significantly reduced activity of hepatic stellate cells as well as reduced deposition of extracellular matrix 2 days after BDL, mice were not protected from inflammation and further fibrosis progression. Conclusions: These data indicate that RvD1 has a limited therapeutic potential to treat cholestatic liver diseases, as it has no significant impact on regression of hepatic necroinflammation and fibrotic changes in bile duct-ligated mice.