Protective effect and mechanism of alpha-lipoic acid on partial hepatic ischemia-reperfusion injury in adult male rats.

Abstract

In order to reduce tissue damage caused by ischemia-reperfusion injury, this study aims to investigate the protective effect and mechanism of ?-lipoic acid on hepatic ischemia-reperfusion injury in rats. The bloodstream of rats was blocked in the left middle and left lateral liver lobes of the liver. Forty rats were randomly divided into two groups: treatment group and injury group. Rats were injected with either 25 mg/1 ml of alpha-lipoic acid (treatment group) or 1 ml of saline (injury group) into the caudal vein 15 min before hepatic ischemia-reperfusion. Rat serum alanine aminotransferase (GPT), glutathione (GSH) and superoxide dismutase (SOD) levels were examined at various time points (1, 3, 6 and 12 h) in both groups. Changes in nuclear factor kappa B P65 (NF-kappaB P65) expression in ischemia-reperfusion liver at various time points after reperfusion (1, 3, 6 and 12 h) were evaluated through immunohistochemistry assay. Changes in macrophage inflammatory protein-2 (MIP-2) mRNA and inducible nitric oxide synthase (iNOS) mRNA expression in ischemic reperfused rat livers were detected by RT-PCR. Serum GPT level was significantly higher in the injury group than in the treatment group (P<0.01). NF-kappaB P65, MIP-2 mRNA and iNOS mRNA expression in ischemic reperfused rat livers were significantly higher in the injury group than in the treatment group (P<0.01). Serum GSH and SOD levels were higher in the treatment group than in the injury group (P<0.01). Alpha-lipoic acid significantly reduced ischemia-reperfusion injury in rat livers. This may be associated to the direct scavenging of oxygen-free radicals, increased GSH production, and the activation of downstream media due to decreased NF-kappaB and GSH consumption.