Abstract
Both chronic and acute (binge) alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD). There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding (Lieber–DeCarli liquid diet model), chronic intragastric EtOH administration (Tsukamoto–French model), and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s) of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.
Highlights
Alcohol consumption, both acute and chronic, is an important social, economic, and clinical problem
alcoholic liver disease (ALD) is manifested as a spectrum of clinical disorders ranging from steatosis to alcoholic hepatitis (AH, a combination of steatosis and inflammation), and may progress further to the more severe forms, cirrhosis and hepatocellular carcinoma
Rodents Models of ALD Utilizing Binge Ethanol Administration: Liver Injury Outcomes and Historically, animal models of ALD utilizing binge EtOH administration have progressed from single or multiple binges alone to single or multiple binges combined with chronic EtOH exposure
Summary
Both acute and chronic, is an important social, economic, and clinical problem. Experimental animal models that effectively reproduce human drinking patterns and mimic the spectrum and severity of alcohol-induced liver injury in humans are a necessity. We discuss the binge alcohol drinking pattern, the effects of binge EtOH intake on blood alcohol concentration (BAC), and review selected studies utilizing current rodent models of ALD that employ binge EtOH administration alone or in combination with chronic EtOH intake, HFD, or endotoxin challenge (Figure 1). Shows effect of long-term chronic EtOH + multiple binges in mice; Examines effect of aging; Shows that model recapitulates features of AH and achieves hepatic fibrosis [29]. Cxcl expression in hepatocytes, hepatic stellate cells and sinusoidal endothelial cells, and adipose tissue
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