Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insu...

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Bibliographic Details
Published in:PloS one 2017-01, Vol.12 (1), p.e0170350-e0170350
Main Authors: Gao, Wanxia, Zhao, Jie, Gao, Zhonghong, Li, Hailing
Format: Article
Language:English
Subjects:
Alcohol use
Alcoholic beverages
Alzheimer's disease
Alzheimers disease
Animals
Antioxidants
Biochemical analysis
Biology and Life Sciences
Chemical engineering
Chemistry
Coexistence
Deactivation
Dextran
Disease Models, Animal
Dosage and administration
Drinking (Alcoholic beverages)
Enzymes
Ethanol
Ethanol - administration & dosage
Ethanol - toxicity
Gene expression
Glycolysis
Health aspects
Immunoprecipitation
Inactivation
Injuries
Iron
Iron - administration & dosage
Iron Overload - complications
Iron Overload - metabolism
Iron Overload - pathology
Iron-dextran complex
Laboratories
Liver
Liver - injuries
Liver - metabolism
Liver - pathology
Liver diseases
Liver Diseases, Alcoholic - complications
Liver Diseases, Alcoholic - metabolism
Liver Diseases, Alcoholic - pathology
Low alcohol
Male
Medicine and Health Sciences
Metabolism
Mice
NAD
NADH
Nicotinamide adenine dinucleotide
Nitration
Nitric oxide
Nitro Compounds - metabolism
Oxidative stress
Oxidative Stress - drug effects
Physical Sciences
Polyclonal antibodies
Proteins
Proteomics
Research and Analysis Methods
Risk factors
Rodents
Science
Triose-phosphate isomerase
Triose-Phosphate Isomerase - antagonists & inhibitors
Triose-Phosphate Isomerase - metabolism
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Summary:It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0170350