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

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.

• Authors: Jia Xiao, Jiteng Wang, Feiyue Xing, Tao Han, Rui Jiao, Emily C Liong, Man-Lung Fung, Kwok-Fai So, George L Tipoe
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e95214 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24740309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cytochrome P-450 CYP2E1 (genetics, metabolism)
• Disease Models, Animal
• Ethanol (administration & dosage)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Fatty Liver, Alcoholic (drug therapy, genetics, metabolism, pathology)
• Female
• Gene Expression Regulation
• Hepatocytes (drug effects, metabolism, pathology)
• I-kappa B Proteins (genetics, metabolism)
• Liver (drug effects, metabolism, pathology)
• MAP Kinase Kinase 4 (genetics, metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (genetics, 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, metabolism)