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Adv Exp Med Biol. 2018;1032:203-221. doi: 10.1007/978-3-319-98788-0_14.

Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer.

Author information

1
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA.
2
Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
3
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Aurora, CO, USA.
4
Department of Clinical Pharmacy, Skaggs School of Pharmacy, University of Colorado, Aurora, CO, USA.
5
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA. vasilis.vasiliou@yale.edu.

Abstract

Excessive consumption of alcohol is a leading cause of lifestyle-induced morbidity and mortality worldwide. Although long-term alcohol abuse has been shown to be detrimental to the liver, brain and many other organs, our understanding of the exact molecular mechanisms by which this occurs is still limited. In tissues, ethanol is metabolized to acetaldehyde (mainly by alcohol dehydrogenase and cytochrome p450 2E1) and subsequently to acetic acid by aldehyde dehydrogenases. Intracellular generation of free radicals and depletion of the antioxidant glutathione (GSH) are believed to be key steps involved in the cellular pathogenic events caused by ethanol. With continued excessive alcohol consumption, further tissue damage can result from the production of cellular protein and DNA adducts caused by accumulating ethanol-derived aldehydes. Much of our understanding about the pathophysiological consequences of ethanol metabolism comes from genetically-engineered mouse models of ethanol-induced tissue injury. In this review, we provide an update on the current understanding of important mouse models in which ethanol-metabolizing and GSH-synthesizing enzymes have been manipulated to investigate alcohol-induced disease.

KEYWORDS:

Acetaldehyde; Alcohol; Aldehyde dehydrogenase; Cancer; Glutathioine; Transgenic; Tumor

PMID:
30362100
DOI:
10.1007/978-3-319-98788-0_14
[Indexed for MEDLINE]

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