Protective effect and mechanism of hemeoxygenase-1 induction on acute liver injury by carbon tetrachloride in rats

Objective To investigate the protective effect and mechanism of hemeoxygenase-1 induction against acute liver injury caused by carbon tetrachloride in rats. Methods Male rats were randomly divided into four groups.The control group received a single dose of corn oil injection.Carbon tetrachloride was injected intraperitoneally(i.p) to establish acute liver injury models in rats.Hemin(50μmol/kg) was administered intraperitoneally 12 hours before CCl4 treatment,with an aim to induce HO-1 protein expression in the liver of rats.The expression of HO-1 protein in the liver of hemin-treated rats was determined by western blot method at different time.After 24 h,all rats were sacrificed to collect blood samples for ALT,AST examination,and liver tissues for analysis of MDA concentration,SOD activity and Caspase-3 activity as well as TNF-α level.Histopathological changes were also investigated. Results It showed that administration of carbon tetrachloride to rats caused a remarkable hepatic damage,characterized by significant elevation of serum ALT,AST levels and liver MDA content,caspase-3 activitiy and TNF-α level combined with a remarkable reduction in liver SOD activity compared with the control group.Histopathological observations revealed severe damage in the liver of CCl4-treated rats.Pretreatment with hemin could induce high expression of HO-1 protein and exert potent protective effects on liver injury,as demonstrated by a significant decrease in ALT,AST levels and MDA concentration,reduction in Caspase-3 activity and TNF-alevel compared with CCl4-treated rats. Conclusion It suggested that induction of HO-1 has a potent protective effect on acute liver injury induced by carbon tetrachloride in rats.HO-1 induction can attenuate severe hepatic damage, which might be due to the alleviation of lipid peroxidation and reduction of Caspase-3 activity or TNF-α level.