New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury

AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid(HA) and sphingosine 1-phophate.METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate(S1P), and HA-S1 P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase(ALT), histological findings, Td T-mediated d UTP-biotin nick end labeling(TUNEL) staining, and transmission electron microscopy(TEM). We also investigated the expressionof proteins associated with apoptosis, hepatoprotection, and S1 P accumulation. RESULTS: S1 P accumulated in the HA-S1 P group livers more than S1 P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1 P group. TEM revealed that the liver sinusoidal endothelial cell(LSEC) lining was preserved in the HA-S1 P group. Moreover, the HA-S1 P group showed a greater increase in the HO-1 protein levels compared to the S1 P group.CONCLUSION: Our results suggest that HA-S1 P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1 P is an effective agent for hepatic ischemia/reperfusion injury.