title: Decreased hepatic iron in response to alcohol may contribute to alcohol-induced suppression of hepcidin.
abstract: Hepatic Fe overload has often been reported in patients with advanced alcoholic liver disease. However, it is not known clearly whether it is the effect of alcohol that is responsible for such overload. To address this lacuna, a time-course study was carried out in mice in order to determine the effect of alcohol on Fe homoeostasis. Male Swiss albino mice were pair-fed Lieber-DeCarli alcohol diet (20 % of total energy provided as alcohol) for 2, 4, 8 or 12 weeks. Expression levels of duodenal and hepatic Fe-related proteins were determined by quantitative PCR and Western blotting, as were Fe levels and parameters of oxidative stress in the liver. Alcohol induced cytochrome P4502E1 and oxidative stress in the liver. Hepatic Fe levels and ferritin protein expression dropped to significantly lower levels after 12 weeks of alcohol feeding, with no significant effects at earlier time points. This was associated, at 12 weeks, with significantly decreased liver hepcidin expression and serum hepcidin levels. Protein expressions of duodenal ferroportin (at 8 and 12 weeks) and divalent metal transporter 1 (at 8 weeks) were increased. Serum Fe levels rose progressively to significantly higher levels at 12 weeks. Histopathological examination of the liver showed mild steatosis, but no stainable Fe in mice fed alcohol for up to 12 weeks. In summary, alcohol ingestion by mice in this study affected several Fe-related parameters, but produced no hepatic Fe accumulation. On the contrary, alcohol-induced decreases in hepatic Fe levels were seen and may contribute to alcohol-induced suppression of hepcidin.
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Joe
authors.initials: J
authors.lastname: Varghese
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Jithu Varghese
authors.initials: JV
authors.lastname: James
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Sreerohini
authors.initials: S
authors.lastname: Sagi
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Subhosmito
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Abitha
authors.initials: A
authors.lastname: Sukumaran
authors.affiliation: 2Department of Pathology,Christian Medical College,Vellore, 632004,Tamilnadu,India.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Ramakrishna
authors.affiliation: 1Department of Biochemistry,Christian Medical College,Vellore, 632002,Tamilnadu,India.
authors.forename: Molly
authors.initials: M
authors.lastname: Jacob
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005234:Fatty Liver; D005293:Ferritins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood / Q000378:metabolism*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D000431:Ethanol; D005293:Ferritins; D064451:Hepcidins; D007501:Iron; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
keywords: ALD alcoholic liver disease; ALT alanine transaminase; Alcoholic liver disease; BMP6 bone morphogenetic protein 6; CYP2E1 cytochrome P2E1; HO-1 haeme oxygenase 1; Hepcidin; Iron; Tfr1 transferrin receptor 1