Browse

Combined metadoxine and garlic oil treatment efficaciously abrogates alcoholic steatosis and CYP2E1 induction in rat liver with restoration of AMPK activity

Cited 41 time in Web of Science Cited 44 time in Scopus
Authors
Ki, Sung Hwan; Choi, Jae Hoon; Kim, Choon Won; Kim, Sang Geon
Issue Date
2007
Publisher
Elsevier
Citation
Chem. Biol. Interact. 169 (2007) 80-90
Keywords
Adenylate Kinase/*metabolismAlcoholism/*complicationsAllyl Compounds/administration & dosage/pharmacology/*therapeutic useAnimalsCytochrome P-450 CYP2E1/*biosynthesisDrug CombinationsEnzyme InductionFatty Liver/*drug therapy/enzymology/etiologyLiver/*drug effects/enzymology/metabolismPyridoxine/administration & dosage/pharmacology/*therapeutic usePyrrolidonecarboxylic Acid/administration &dosage/pharmacology/*therapeutic useRatsRats, Sprague-DawleySulfides/administration & dosage/pharmacology/*therapeutic useTriglycerides/metabolism
Abstract
Alcoholic steatosis is the earliest and most common response to heavy alcohol intake, and may precede more severe forms of liver injury. Accumulation of fat, largely triglyceride, in hepatocytes results from the inhibition of fatty acid oxidation and excessive oxidative stress involving CYP2E1. This study evaluated the therapeutic effects of metadoxine, garlic oil or their combination on alcoholic steatosis. Feeding rats an alcohol-containing diet for 4 weeks elicited an increase in hepatic triglyceride content and induced CYP2E1. The concurrent administration of metadoxine and garlic oil (MG) to rats during the last week of the diet feeding efficaciously abrogated both fat accumulation and CYP2E1 induction as compared to the individual treatment at higher doses. Histopathology confirmed the ability of MG combination to inhibit lipid accumulation. Blood biochemistry verified improvement of liver function in rats treated with MG. Alcohol administration resulted in a decrease in AMP-activated protein kinase-alpha (AMPKalpha) phosphorylation, which was restored by MG treatments. Recovery of AMPK activity by MG was supported by an increase in acetyl-CoA carboxylase phosphorylation. Hepatic fatty acid synthase (FAS) expression was markedly decreased after alcohol consumption, which correlated with a decrease in AMPK activity and a commensurate increase in lipid content. Combined MG treatments caused restoration of the FAS level. These results demonstrate that the combination of MG effectively treats alcoholic steatosis with CYP2E1 inhibition, which may be associated with the recovery of AMPK activity, promising that the combination therapy may constitute an advance in the development of clinical candidates for alcoholic steatosis.
ISSN
0009-2797 (Print)
Language
English
URI
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T56-4NWCDFM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7102f65c27ccaed7873e4031e84d8b88

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17606256

https://hdl.handle.net/10371/22175
DOI
https://doi.org/10.1016/j.cbi.2007.05.008
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Program in Clinical Pharmacology (협동과정-임상약리학전공)Journal Papers (저널논문_협동과정-임상약리학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse