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

• Published in: PloS one 2014-04, Vol.9 (4), p.e95214
• Main Authors: Xiao, Jia, Wang, Jiteng, Xing, Feiyue, Han, Tao, Jiao, Rui, Liong, Emily C, Fung, Man-Lung, So, Kwok-Fai, Tipoe, George L
• Format: Article
• Language: English
• Subjects: Abnormalities; Aging; Alcohol; Animals; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Biology and life sciences; Body weight; Care and treatment; Cell culture; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P-450 CYP2E1 - metabolism; Cytochrome P450; Diagnosis; Disease Models, Animal; Ethanol; Ethanol - administration & dosage; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Fatty liver; Fatty Liver, Alcoholic - drug therapy; Fatty Liver, Alcoholic - genetics; Fatty Liver, Alcoholic - metabolism; Fatty Liver, Alcoholic - pathology; Female; Fisheries; Gene Expression Regulation; Health aspects; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Immunoglobulins; Immunology; JNK protein; Kinases; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cirrhosis; Liver diseases; Lycium barbarum; MAP kinase; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; Medical research; Medical treatment; Medicine; Medicine and Health Sciences; NF-kappa B - genetics; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Palmitates - pharmacology; Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Restoration; Risk factors; Rodents; Signal Transduction; Studies; Weight Loss - drug effects; Weight reduction; Xanthophylls - pharmacology; Zeaxanthin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095214

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.