Effect of trolox on altered vasoregulatory gene expression in hepatic ischemia/reperfusion

This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemiain vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET-1), potent vasoconstrictor peptide, its receptor ETA and ETB, vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxidation levels were markedly increased after l/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the l/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by l/R, an increase which was prevented by Trolox. The mRNA levels for ETA receptor was significantly decreased, whereas ETB receptor transcript increased in the l/R group. The increase in ETA was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/ R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-a significantly increased in l/R group and Trolox also attenuated this increase. Our find-ings suggest that l/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.