NADPH Combined With VE Produces Synergistic Effects In CCl4-induced Liver Damage And Its Mechanism

Objective:This study aims to investigate the protective mechanism of NADPH combinted with VE in CCl4-induced liver injury.Methods:Carbon tetrachloride(CC14)is a frequently used chemical to experimentally induce liver toxicity.To investigate the function of NADPH and VE in liver injury,we subjected ICR mice to acute CCl4-induced liver damage.The determination of alkaline phosphates(ALP),total bilirubin(TB)by using Chemistry-Immuno Analyzer.Alanine transaminase(ALT),aspartate transaminase(AST)was determined by using a colorimetric assay kit.The liver tissue specimens stained with hematoxylin and eosin(HE)or oil red O for analysis of lipid storage in the liver.Western blotting was used to detect the changes of apoptosis-related protein.Immunofluorescence methods were used to observe the distribution of Nrf2 protein in mice liver.Results:First,we demonstrated the protective effect of NADPH and VE on CC14-induced liver injury,and found that NADPH combined with VE produces synergistic effects in CC14-induced liver injury according to King’s Law.Subsequently,we find NADPH combined with VE can scavenge the free radical,increase in tissue and serum antioxidative capacity(increase in SOD and CAT).We also find that apoptosis-related protein were significantly increased in the CCl4 group,after treatments of with combined NADPH and VE,we find that the increase of hepatocyte-related apoptotic proteins induced by CC14 was significantly reduced.NADPH combined with VE can activate the nuclear localization of the transcription factor Nrf2 and increase the level of its downstream protein GCLC;Conclusions:NADPH combined with VE produce synergistic effects on liver injury induced by CC14.This effect of NADPH and VE related to increase antioxidative capacity,inhibits the apoptosis and activation of Nrf2.