title: 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.
abstract: 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.
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, P. R. China.|Basis medical college, Hubei University of Science and Technology, Xianning, P. R. China.
authors.forename: Wanxia
authors.initials: W
authors.lastname: Gao
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, P. R. China.|Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan, P. R. China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, P. R. China.|Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan, P. R. China.
authors.forename: Hailing
authors.identifier: http://orcid.org/0000-0002-5282-586X
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D007501:Iron / Q000008:administration & dosage; D019190:Iron Overload / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009574:Nitro Compounds / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014305:Triose-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D009574:Nitro Compounds; D000431:Ethanol; D007501:Iron; D014305:Triose-Phosphate Isomerase