Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response.

Ting Xia,Yu Zheng,Jia Song,Jin Zhang,Bo Zhang,Peng Du,Jiahui Yao,Chaoya Zhao,Wenhui Duan,Min Wang

doi:10.3390/nu10070805

Abstract

Shanxi aged vinegar (SAV) is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.). The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS) level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

Highlights

Alcohol is primarily metabolized in liver, and excess alcohol consumption can induce liver damage [1]
The primary antibodies against rabbit nuclear factor erythroid-2-related factor 2 (Nrf2), nicotinamide quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), Phospho-IκB (p-IκB) and GAPDH were obtained from Abcam (Cambridge, MA, USA)
The primary antibodies against rabbit inducible nitric oxide synthase (iNOS), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), Phospho-NF-κB p65 (p-NF-κB p65) and the secondary horseradish peroxidase (HRP)-labelled goat-anti-rabbit and goat-anti-mouse antibodies were purchased from Cell Signaling

Summary

Introduction

Alcohol is primarily metabolized in liver, and excess alcohol consumption can induce liver damage [1]. It has been demonstrated that alcohol-induced liver injury is one of the leading causes of alcohol-related death, which is characterized by progressive damage of the liver from fibrosis to cirrhosis [2,3]. Acute alcohol consumption leads to elevation of liver function enzymes, acute liver inflammation and metabolism disorders including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation [4,5]. Chronic alcohol exposure induces continuous and progressive inflammation and lipid metabolism disorders, which cause alcoholic hepatitis, fibrosis, cirrhosis and even hepatocarcinoma [6]. Several studies have revealed that oxidative stress and inflammation play important roles in the pathogenesis of acute or chronic alcohol-induced liver injury [7,8].

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