Effects of chronic alcohol and excessive iron intake on mitochondrial DNA damage in the rat liver.
10.4163/jnh.2015.48.5.390
- Author:
Jung Eun PARK
1
;
Jeong Ran LEE
;
Jayong CHUNG
Author Information
1. Department of Food and Nutrition, Kyung Hee University, Seoul 02447, Korea. jchung@khu.ac.kr
- Publication Type:Original Article
- Keywords:
alcoholic liver injury;
iron;
mitochondrial DNA
- MeSH:
Alanine Transaminase;
Alcoholics;
Animals;
Aspartate Aminotransferases;
Diet;
DNA;
DNA, Mitochondrial*;
Electron Transport Complex IV;
Ethanol;
Gene Expression;
Genes, Mitochondrial;
Humans;
Inflammation;
Iron*;
Liver*;
Male;
Malondialdehyde;
NADH Dehydrogenase;
Necrosis;
Polymerase Chain Reaction;
Rats*;
Rats, Sprague-Dawley;
Real-Time Polymerase Chain Reaction;
RNA, Messenger
- From:Journal of Nutrition and Health
2015;48(5):390-397
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: In this study, we investigated the effects of chronic alcohol and excessive iron intake on mitochondrial DNA (mtDNA) damage and the progression of alcoholic liver injury in rats. METHODS: Twenty-four Sprague-Dawley male rats were divided into four groups (Control, EtOH, Fe, and EtOH + Fe), and fed either control or ethanol (36% of total calories) liquid diet with or without 0.6% carbonyl iron for eight weeks. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, liver malondialdehyde concentrations were measured by colorimetric assays. Liver histopathology was examined by Hematoxylin-eosin staining of the fixed liver tissues. The integrity of the hepatic mtDNA and nuclear DNA was measured by long-range PCR. The gene expression levels of cytochrome c oxidase subunit 1 (Cox1) and NADH dehydrogenase subunit 4 (Nd4) were examined by real-time PCR. RESULTS: Serum ALT and AST activities were significantly higher in the EtOH+Fe group, as compared to the Control group. Similarly, among four groups, liver histology showed the most severe lipid accumulation, inflammation, and necrosis in the EtOH + Fe group. PCR amplification of near-full-length (15.9 kb) mtDNA showed more than 50% loss of full-length product in the liver of the EtOH + Fe group, whereas amounts of PCR products of a nuclear DNA were unaffected. In addition, the changes in the mtDNA integrity showed correlation with reductions in the mRNA levels of mitochondrial gene Cox1 and Nd4. CONCLUSION: Our data suggested that the liver injury associated with excessive iron and alcohol intake involved mtDNA damage and corresponding mitochondrial dysfunction.
