Abstract

In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-κB) through the restoration of its inhibitor kappa B alpha (IκBα), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases.

Highlights

  • The abuse of alcohol is a severe social problem in the world with heavy burden in both health and economics

  • When zeaxanthin dipalmitate (ZD) was cotreated from the 5th week to the 10th week, rats from the ALD+ZD group increased in body weight when compared with the alcoholic fatty liver disease (AFLD) group (p,0.05)

  • In recent years, emerging evidence suggests that several kinds of herbal derivatives may play protective and therapeutic roles against AFLD, such as wolfberry [21], resveratrol [22], green tea [23], and Control Ethanol Ethanol+ZD ip38 iJNK iERK Ethanol+ip38 Ethanol+iJNK Ethanol+iERK Ethanol+ZD+ip38 Ethanol+ZD+iJNK Ethanol+ZD+iERK

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Summary

Introduction

The abuse of alcohol is a severe social problem in the world with heavy burden in both health and economics. The prevalence of AFLD is influenced by many factors, the abuse of alcohol, and the gender discrepancy, genetic defects and other environmental factors, since only 1 in 5 heavy drinkers develops alcoholic hepatitis [2]. ASH is characterized by the presence of inflammatory foci within the liver and the occurrence of macrophage activation and chemoattraction [4]. These mechanisms are closely associated with the production of reactive oxygen species (ROS) induced by ethanol and its metabolites, as well as the activation of innate immunity (e.g. the production of pro-inflammatory cytokines and chemokines) [5]. Administration of therapy directed against the initiation and progression of AFLD should at least target one or several key pathological events related to AFLD, such as steatosis, hepatic oxidative stress, and inflammation

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