Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

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.

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

“…( 7,8,28 ) The Lieber‐DeCarli feeding model is an accepted model of ALD that results in features of human ALD, including steatosis, inflammation, and liver fibrosis. ( 39 ) Results of these studies suggested that alcohol promotes HCC progression in mice through increasing hepatocyte proliferation, ( 7,8 ) increasing inflammation and tumor‐associated macrophage infiltration, ( 8,28 ) and promoting epithelial‐mesenchymal transition. ( 8,28 ) However, relative contributions of these pathways are unknown.…”

Alcohol-related Liver Disease: Areas of Consensus, Unmet Needs and Opportunities for Further Study

“…An acute binge in animals with chronic alcohol feeding increases liver damage and neutrophil infiltration (63). The continuous intragastric alcohol feeding model with weekly binge achieves most features of alcoholic hepatitis (64)(65)(66) including unique activation of the pyroptotic caspase 4/11-gasdermin-D pathway and its association with liver bacterial load as validated in severe alcoholic hepatitis patients but is expensive and requires special surgical expertise to develop (66).…”

Aplysin Protects Against Alcohol‐Induced Liver Injury Via Alleviating Oxidative Damage and Modulating Endogenous Apoptosis‐Related Genes Expression in Rats

“…Alcohol abuse-associated liver injury (ALD), a multifaceted pathologic change characterized by a broad spectrum of liver injury ranging from hepatic steatosis and hepatitis to fibrosis to cirrhosis, even leading to hepatocellular carcinoma (Ghosh Dastidar, Warner, Warner, McClain, & Kirpich, 2018). Accumulating evidence has suggested that oxidative stress plays a central role in the development of alcoholic liver injury (Dey & Cederbaum, 2006).…”