Alpha-lipoic acid attenuates methionine choline deficient diet-induced steatohepatitis in C57BL/6 mice.

Abstract

AIMS:

Non-alcoholic steatohepatitis (NASH) is a liver disease that causes fat accumulation, inflammation and fibrosis. Increased oxidative stress contributes to hepatic inflammation and fibrosis by upregulation of Cytochrome P450 2E1 (CYP2E1), endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) activity. This study examined whether alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, prevents steatohepatitis through the inhibition of several pathways involved in hepatic inflammation and fibrosis.

MAIN METHODS:

C57BL/6 mice were fed an MCD diet with or without ALA for 4weeks. Liver sections from mice on control or MCD diets with or without ALA were stained with hematoxylin-eosin, oil red O, and anti-4-HNE antibody. The effects of ALA on methionine-choline deficient MCD-diet induced plasma AST and ALT as well as tissue TBARS were measured. The effects of ALA on CYP2E1 expression, ER stress, MAPK levels, and NF-κB activity in MCD diet-fed mice liver were measured by northern and western blot analysis.

KEY FINDINGS:

Dietary supplementation with ALA reduced MCD diet-induced hepatic lipid accumulation, hepatic inflammation, TBARS, 4-HNE, and plasma ALT and AST levels. These effects were associated with a reduced expression of CYP2E1 and reduced ER stress and MAPK and NF-κB activity.

SIGNIFICANCE:

Taken together, the results of the present study indicate that ALA attenuates steatohepatitis through inhibition of several pathways, and provide the possibility that ALA can be used to prevent the development and progression of non-alcoholic fatty liver disease in patients who have strong risk factors for NASH.

• Authors: Ae-Kyung Min, Mi-Kyung Kim, Hye-Soon Kim, Hye-Young Seo, Ki-Up Lee, Jung-Guk Kim, Keun-gyu Park, In-Kyu Lee
• Journal: Life sciences (Life Sci) Vol. 90 Issue 5-6 Pg. 200-5 (Jan 30 2012) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 22154902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• NF-kappa B
• Thiobarbituric Acid Reactive Substances
• Thioctic Acid
• Methionine
• Cytochrome P-450 CYP2E1
• Alanine Transaminase
• Mitogen-Activated Protein Kinases
• Choline

Topics

• Alanine Transaminase (blood, metabolism)
• Analysis of Variance
• Animals
• Antioxidants (metabolism)
• Choline (metabolism)
• Choline Deficiency (metabolism)
• Cytochrome P-450 CYP2E1 (metabolism)
• Diet (adverse effects)
• Disease Models, Animal
• Endoplasmic Reticulum Stress (drug effects)
• Fatty Liver (chemically induced, prevention & control)
• Humans
• Inflammation (metabolism)
• Liver (drug effects, metabolism, pathology)
• Male
• Methionine (deficiency)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Thioctic Acid (administration & dosage, metabolism)