N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice

BACKGROUND:Toll-like receptor 2 and 4(TLR2/4)may play important roles in ischemia-reperfusion(I/R)injury, and N-acetylcysteine(NAC)can prevent the generation of reactive oxygen species(ROS)induced by I/R injury.This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS:BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group(SH),a hepatic ischemia/ reperfusion group(I/R)or a NAC pretreated,hepatic I/R group(I/R-NAC).The levels of TNF-αin the portal vein and plasma alanine aminotransferase(ALT)were measured at 1 and 3 hours after reperfusion.The lung wet-to-dry ratio was measured,and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS:Compared with the I/R group,the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05).The levels of portal vein TNF-αand plasma ALT increased continuously in the I/R group at 1 and 3 hours of reperfusion compared with the SH group;however,they declined significantly in the group pretreated with NAC (P<0.05).The extent of lung edema was relieved in the I/ R-NAC group compared with the I/R group(P<0.05).CONCLUSIONS:TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury.NAC inhibited the activation of TLR2/4 and the induction of TNF-α resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice