Article ; Online: Iron overload in alcoholic liver disease: underlying mechanisms, detrimental effects, and potential therapeutic targets.
Cellular and molecular life sciences : CMLS
2022 Volume 79, Issue 4, Page(s) 201
Abstract: Alcoholic liver disease (ALD) is a global public health challenge due to the high incidence and lack of effective therapeutics. Evidence from animal studies and ALD patients has demonstrated that iron overload is a hallmark of ALD. Ethanol exposure can ... ...
Abstract | Alcoholic liver disease (ALD) is a global public health challenge due to the high incidence and lack of effective therapeutics. Evidence from animal studies and ALD patients has demonstrated that iron overload is a hallmark of ALD. Ethanol exposure can promote iron absorption by downregulating the hepcidin expression, which is probably mediated by inducing oxidative stress and promoting erythropoietin (EPO) production. In addition, ethanol may enhance iron uptake in hepatocytes by upregulating the expression of transferrin receptor (TfR). Iron overload in the liver can aggravate ethanol-elicited liver damage by potentiating oxidative stress via Fenton reaction, promoting activation of Kupffer cells (KCs) and hepatic stellate cells (HSCs), and inducing a recently discovered programmed iron-dependent cell death, ferroptosis. This article reviews the current knowledge of iron metabolism, regulators of iron homeostasis, the mechanism of ethanol-induced iron overload, detrimental effects of iron overload in the liver, and potential therapeutic targets. |
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MeSH term(s) | Animals ; Hepatocytes/metabolism ; Humans ; Iron/metabolism ; Iron Overload/complications ; Iron Overload/therapy ; Liver Diseases, Alcoholic/metabolism |
Chemical Substances | Iron (E1UOL152H7) |
Language | English |
Publishing date | 2022-03-24 |
Publishing country | Switzerland |
Document type | Journal Article ; Review |
ZDB-ID | 1358415-7 |
ISSN | 1420-9071 ; 1420-682X |
ISSN (online) | 1420-9071 |
ISSN | 1420-682X |
DOI | 10.1007/s00018-022-04239-9 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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