Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway

Jia Xiao; Jiteng Wang; Feiyue Xing; Tao Han; Rui Jiao; Emily C Liong; Man-Lung Fung; Kwok-Fai So; George L Tipoe

doi:10.1371/journal.pone.0095214

Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway

PLoS One. 2014 Apr 16;9(4):e95214. doi: 10.1371/journal.pone.0095214. eCollection 2014.

Authors

Jia Xiao¹, Jiteng Wang², Feiyue Xing³, Tao Han², Rui Jiao⁴, Emily C Liong⁵, Man-Lung Fung⁶, Kwok-Fai So⁷, George L Tipoe⁸

Affiliations

¹ Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China; Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
² School of Fishery, Zhejiang Ocean University, Zhoushan, China.
³ Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China.
⁴ Department of Food Science and Engineering, Jinan University, Guangzhou, China.
⁵ Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁶ Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁷ GMH Institute of Central Nervous System Regeneration, Jinan University, Guangzhou, China; Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁸ Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology*
Apoptosis / drug effects
Cytochrome P-450 CYP2E1 / genetics
Cytochrome P-450 CYP2E1 / metabolism
Disease Models, Animal
Ethanol / administration & dosage*
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism
Fatty Liver, Alcoholic / drug therapy*
Fatty Liver, Alcoholic / genetics
Fatty Liver, Alcoholic / metabolism
Fatty Liver, Alcoholic / pathology
Female
Gene Expression Regulation
Hepatocytes / drug effects
Hepatocytes / metabolism
Hepatocytes / pathology
I-kappa B Proteins / genetics
I-kappa B Proteins / metabolism
Liver / drug effects
Liver / metabolism
Liver / pathology
MAP Kinase Kinase 4 / genetics
MAP Kinase Kinase 4 / metabolism
NF-KappaB Inhibitor alpha
NF-kappa B / genetics
NF-kappa B / metabolism
Oxidative Stress / drug effects
Palmitates / pharmacology*
Protective Agents / pharmacology*
Rats
Rats, Sprague-Dawley
Signal Transduction
Weight Loss / drug effects
Xanthophylls / pharmacology*
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Antioxidants
I-kappa B Proteins
NF-kappa B
Nfkbia protein, rat
Palmitates
Protective Agents
Xanthophylls
NF-KappaB Inhibitor alpha
Ethanol
zeaxanthin dipalmitate
Cytochrome P-450 CYP2E1
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4

Grants and funding

This work was supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. Y3090624); Small Project Funding, University Research Committee, HKU; General Research Fund, University Grant Council, Hong Kong SAR; and the Azalea (1972) Endowment Fund to KFS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.