Resolvin D1 protects against hepatic ischemia/reperfusion injury in rats

Inflammatory responses play an important role in the tissue damage during hepatic ischemia/reperfusion (I/R). Some resolvins have been shown to have protective properties in reducing I/R injury in the heart and kidney. The aim of the study was to investigate the effects of resolvin D1 (RvD1) on hepatic I/R.

Partial warm ischemia was produced in the left and middle hepatic lobes of Sprague-Dawley rats for 60 min, followed by 6h of reperfusion. Rats received either RvD1 (5 μg/kg) or vehicle by intravenous injection prior to ischemia. On the basis of treatment with RvD1, some rats further received the PI3K inhibitor LY294002. Blood and tissue samples from the groups were collected after 6-h reperfusion.

Our results indicate that the RvD1 receptor ALX/FPR2 is present in liver, and that pretreatment with RvD1 prior to I/R insult significantly blunted I/R-induced elevations of alanine aminotransferase (AST) and aspartate aminotransferase (ALT), and significantly improved the histological status of the liver. Moreover, RvD1 significantly inhibited inflammatory cascades, as demonstrated by attenuations of IL-6, TNF-α and myeloperoxidase levels. Reduced apoptosis, and increased phosphorylation of Akt, were observed in the RvD1 group compared with the control I/R group. These effects of RvD1 on hepatic I/R injury were diminished by the PI3K inhibitor.

Administration of RvD1 prior to hepatic I/R attenuates hepatic injury, at least in part through inhibition of inflammatory response and enhancement of phosphorylation of Akt.