Protective Effect of Pterostilbene Against Acetaminophen-induced Acute Liver Injury in Mice Based on Keap1/Nrf2/Mitochondria Pathway

OBJECTIVE To observe the protective effect of pterostilbene(PTE) on acute liver injury induced by acetaminophen(APAP) in mice, and to explore related mechanisms. METHODS Acute liver injury model of mice was established by APAP(250 mg·kg^-1), PTE was given 15, 30, 60 mg·kg^-1 by intragastric for 15 d pre-protection. The serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TP) and albumin(Alb) were determined by automatic biochemical analyzer and the albumin/globulin(A/G) ratio was calculated. The liver tissue was stained by hematoxylin-eosin(HE) staining and liver histopathology detection and grading evaluation were calculated. The superoxide dismutase(SOD), reduced glutathione(GSH), malondialdehyde(MDA) level were assayed by related kits. The mitochondrial membrane potential was measured by JC-1. Apoptosis of hepatic cell were detected by TUNEL staining. The protein expressions of Bax, cytochrome C, nuclear factor erythroid 2-related factor-2(Nrf2) and Keleh-like ECH-associated protein 1(Keap1) were detected by Western blotting. RESULTS Compared with APAP model group, the serum ALT and AST values of mice in different concentrations of PTE group were significantly reduced(P<0.01), and Alb, TP and A/G ratio were significantly increased(P<0.05 or P<0.01); the histopathological grade of liver damage reduced; the SOD, GSH level of liver tissue significantly increased(P<0.01), and MDA level significantly decreased(P<0.01); moreover, the mitochondrial membrane potential increased(P<0.01); TUNEL staining results showed that apoptosis of hepatocytes was significantly reduced in PTE group. Compared with APAP model group, the protein expression of cytoplasmic Bax in PTE group was significantly increased(P<0.05 or P<0.01) while cytochrome C significantly decreased(P<0.01), the expression of Bax in the corresponding mitochondria was significantly decreased(P<0.01), cytochrome C significantly increased(P<0.01). The whole Nrf2 protein expression was increased(P<0.01) while the Keap1 decreased(P<0.01), whats more, the expression of nuclear Nrf2 increased(P<0.01) and the expression of cytoplasmic Nrf2 increased(P<0.01). CONCLUSION PTE can protect APAP-induced acute liver injury. The mechanism may be related to the up-regulation of Nrf2 level, inhibition of oxidative stress and protected the mitochondrial function by PTE.