Alcoholic liver disease: Utility of animal models

Abstract

Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats

“…Excessive drinking can lead to different degrees of alcoholic liver injury, which is reversible during early stages of liver injury. In this study, our liver injury model, which was induced by ethanol, is the usually used ALD animal model for evaluating the hepatoprotective effects of drugs [5,40,41,42]. Currently, liver injury can be evaluated by monitoring serum biomarkers such as ALT, AST and ALP [43].…”

Inflammation in Primary and Metastatic Liver Tumorigenesis–Under the Influence of Alcohol and High-Fat Diets

“…Specifically, diets high in saturated fat are more obesogenic than diets enriched in mono-and poly-unsaturated fatty acids [51]. Current models of ALD vary in ethanol dosage, route of administration and the duration of exposure, however none of these models recapitulate the full spectrum and timeline of ALD pathogenesis, including the development of fibrosis [52]. Combining ethanol feeding with a second hit such as carbon tetrachloride, a hepatotoxin, does result in liver fibrosis, but importantly, this does not reflect the pathology of human ALD [52,53].…”

“…Current models of ALD vary in ethanol dosage, route of administration and the duration of exposure, however none of these models recapitulate the full spectrum and timeline of ALD pathogenesis, including the development of fibrosis [52]. Combining ethanol feeding with a second hit such as carbon tetrachloride, a hepatotoxin, does result in liver fibrosis, but importantly, this does not reflect the pathology of human ALD [52,53]. These models require improvement in order to more accurately mimic the course of human ALD, although they have provided essential understanding as to mechanisms of alcohol-induced toxicity in the liver.…”

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

“…Therefore, hepatic diseases are highly likely to be fatal, and studies targeting the liver have been actively conducted [ 6 ]. In addition to basic research aimed at developing animal models of liver disease [ 7 ] and exploring liver disease treatments [ 8 ], the development of efficient methods to introduce foreign genes into mouse hepatocytes in vivo is important. Hydrodynamics-based gene delivery (HGD) is an efficient method that enables in vivo transfer of nucleic acids (NAs) into mouse hepatocytes via the caudal vein [ 9 , 10 ].…”