Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice.

Chun-Qiu Hu,Yong-Di Hu,Xiao-Jing Liu,Lan-Lan Chu,Lin Fu,De-Xiang Xu,Guo-Xiu Wang,Hua Wang,Qing-Li Bo,Yan Lu

doi:10.1155/2020/5715893

Abstract

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (inos), two NADPH oxidase subunits p47phox and gp91phox, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase (sod) 1 and gshpx. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

Highlights

Alcohol abuse is a serious public health concern responsible for a major cause of morbidity and mortality worldwide [1]
The effects of vitamin D deficiency on chronic alcohol-induced liver injury were investigated in a mouse model
Our results suggest that vitamin D deficiency which aggravates chronic alcohol-induced liver injury is associated with promoting hepatic inflammation and oxidative stress

Summary

Introduction

Alcohol abuse is a serious public health concern responsible for a major cause of morbidity and mortality worldwide [1]. Chronic heavy drinking results in alcoholic liver disease (ALD), characterized by a varied spectrum of liver injury ranging from simple steatosis to alcoholic hepatitis, necrosis, progressive fibrosis, and even hepatocellular carcinoma [2]. Approximately 3.3 million people die each year from alcohol consumption, which accounts for approximately 5.9% of all deaths [3]. Excessive alcohol and its metabolites activate cytochrome P450 2E1 (CYP2E1) resulting in excess production of reactive oxygen species (ROS) [5]. Excess ROS induces depletion of antioxidants, hepatic oxidative stress, and damage to DNA, proteins, and lipids [6]

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