Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation.

Guiyang Wang,Cheng Xin,Kewei Li,Fu Li,Peng Xiu

doi:10.1155/2014/273692

Guiyang Wang, Cheng Xin + Show 3 more

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https://doi.org/10.1155/2014/273692

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Abstract

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats. Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays. Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1. Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

Highlights

The mechanisms of hepatic damage caused by cholestasis are complicated
In the bile duct ligation (BDL) group, 1 died from duodenal rupture caused by operation on day 2 and 1 rat died of abdominal infection due to bile leakage on day 6 after operation
Wang et al [20] suggested that vitamin A derivatives such as retinoic acid inhibited liver fibrosis induced by BDL by reducing the expression of transforming growth factor-β1, connective tissue growth factor, and tissue inhibitors of metalloproteinase-1, diminishing the inhibition of tissue inhibitors of metalloproteinase-1 on matrix metalloproteinase-2 and matrix metalloproteinase-13 promoting the activity of matrix metalloproteinase-2 and matrix metalloproteinase-13

Summary

Introduction

The mechanisms of hepatic damage caused by cholestasis are complicated. Recent studies have shown that reactive oxygen species (ROS) play a major role in the pathogenesis of cholestasis [1,2,3]. The administration of antioxidants has been shown to exert beneficial effects in the prevention of cholestasis liver injury [5,6,7,8,9]. In this way, maintaining the balance between oxidation and antioxidant systems could be an important therapeutic target for cholestasis. Heme oxygenase 1 (Ho1) and NADPH-quinone oxidoreductase 1 (Nqo1) are phase II detoxification enzymes They are regulated by the Nrf2 [12,13,14]. Induction of Nrf2/ARE-dependent antioxidant enzymes and phase II detoxification is one of the major cellular defense mechanisms against oxidative stresses [11, 15, 16]

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