Vitamin A Alleviate Extrahepatic Cholestasis Liver Injury Via Nrf2/NQO1Pathway

AIM: To investigate the role of vitamin A on liver damage induced by bile ductligation (BDL) in rats and its possible mechanism.METHODS: A total of30male Wistar rats were randomly divided into three groups:sham group(Control), bile duct ligated (BDL)group, and BDL treated with vitaminA(BDL+VitA)group. The common bile duct was isolated from the surroundingtissues in control group;BDL group underwent the same procedure and the commonbile duct was further doubly ligated with a4–0silk suture and wastransected between the two ligatures. Vitamin A-treated rats received dailyadministration of vitamin A (Retinyl acetate)100,000I.U./kg dissolved in beanoil by gavage, while those in control group and BDL group were only administeredwith equal volume bean oil. Two weeks after treatment, blood serum and hepatictissue sampled for studies. liver function was evaluated by the level of alanineaminotransferase (ALT),aspertate aminotransferase (AST), alkaline phosphatase(ALP)and total bilirubin(TBIL) in serum; the hepatic oxidative status was estimatedby measuring a battery of biochemical markers (i.e., malondialdehyde(MDA),catalase (CAT),glutathione (GSH)and total superoxide dismutase (T-SOD);the retinol and retinyl palmitate liver contents were analyzed by high performanceliquid chromatography(HPLC) and liver pathologic changes were observed byhematoxylin and eosin staining；the protein levels of nuclear factor erythroid2-related factor (Nrf2) and NADPH-quinone oxidoreductase1(NQO1) in liver tissuewere determined by immunohistochemical techniques and western blotting.RESULTS:Periportal inflammation with bile ductular proliferation was observed in BDL group,which can be alleviated with vitamin A treatment for2weeks. Compared with control group, the levels of retinol and retinyl palmitate in the liver tissue were significantlydecreased in the BDL group(P <0.05), the levels of ALT, AST, ALP and TBIL inserum increased(P <0.05), MDA in hepatic increased and CAT, GSH and T-SODdecreased(P<0.05).Vitamin A administration signifcantly restored contents ofretinoids in liver, the liver function markers(ie.,ALT, AST, ALP, TBIL)and MDA inhepatic significantly decreased(P <0.05),the contents of CAT, GSH and T-SODsignificantly increased(P<0.05); the expression level of Nrf2and NQO1inBDL+VitA group is increased significantly compared with the control group andBDL group(P <0.05).CONCLUSION: Vitamin A alleviated oxidative stress and improved liver injury inbile duct ligation rats which may be related to the activation of Nrf2/NQO1pathway.