Alcohol and iron: a complex relationship

Sandra HelinskiLeave a Comment

Sebastian Mueller

Department of Internal Medicine, Salem Medical Center and

Center for Alcohol Research, University of Heidelberg

Zeppelinstraße 11 – 33

69121 Heidelberg, Germany

 

sebastian.mueller@urz.uni-heidelberg.de

www.sebmueller.com

 

 

Alcoholic liver disease (ALD) is the major liver disease in the developed world. It is characterized by hepatic iron overload in ca. 50% of all patients which is an independent factor of disease progression, hepatocellular carcinoma and survival. Since simple phlebotomy does not allow the efficient removal of excess iron in ALD, a better understanding of the underlying mechanisms is urgently needed to identify novel targeted treatment strategies. Multiple sides of the cellular and systemic iron homeostasis are affected during alcohol consumption with the liver being in the epicenter. It is not only an important iron storage side but also secretes the 25 amino acid peptide hepcidin, the central master switch of systemic iron homeostasis. Hepcidin controls both iron uptake in the small bowl and the release of iron from macrophages.  Notably, hepcidin is not only modulated by only iron itself but also reactive oxygen species, namely hydrogen peroxide (H2O2). For instance, depending on the level, H2O2 may both strongly suppress and induce the expression of hepcidin that could partly explain the anemia and iron overload observed in these patients. Novel recent suggest that H2O2-mediated hepcidin regulation is drastically amplified under hypoxic conditions which is also a hallmark of ethanol metabolism. Moreover, new clinical data from ongoing prospective studies indicate an important role of ethanol-mediated hemolysis directly interfering with hecpidin expression. Current strategies include the development of hepcidin-mimicking drugs, a more optimal identification of ALD subcohorts with distinct patterns of iron dysregulation and matched therapeutic approaches and novel strategies to detect liver iron in a truly non-invasive, bedside fashion.

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