A mini-review of the rodent models for alcoholic liver disease: shortcomings, application, and future prospects

Abstract

Rodents are the most common models in studies of alcoholic liver disease (ALD). Although several rodents ALD models have been established and multiple mechanisms have been elucidated based on them, these models have some non-negligible shortcomings, specifically only inducing early stage (mainly steatosis, slight to moderate steatohepatitis) but not the whole spectrum of human ALD. The resistance of rodents to advanced ALD has been suggested to be due to the physiological differences between rodents and human beings. Previous studies have reported significant interstrain differences in the susceptibility to ethanol-induced liver injury and in the manifestation of ALD (such as different alteration of lipid profiles). Therefore, it would be interesting to characterize the manifestation of ethanol-induced liver damage in various rodents, which may provide a recommendation to investigators of ALD. Furthermore, more severe ALD models need to be established for the study of serious ALD forms, which may be achieved by using genetic modified rodents.

Enhanced lupus progression in alcohol‐administered Fc gamma receptor‐IIb–deficiency lupus mice, partly through leaky gut‐induced inflammation

“…As such, the rate of alcohol metabolism in rodents is higher than that in humans as mice and rats metabolize ethanol at the rate of 550 and 300 mg −1 kg −1 h −1 , respectively, whereas the rate in humans is 100 mg −1 kg −1 h −1 38 . As the dose of alcohol administration in the rodent model is usually higher than that in human patients, 39,40 the model might represent patients with significant alcohol consumption. Accordingly, the standard drink is 14 g of alcohol for 60–80‐kg humans (0.18–0.23 g of alcohol per kg body weight) and the recommended 2 or less standard drink per day in humans 41,42 is much lower than the alcohol administration in our model (4.2 g of alcohol per kg mouse body weight per day).…”

Advancements in the Alcohol-Associated Liver Disease Model

“…This is also why patients with end-stage ALD usually have end-stage viral hepatitis, diabetes, and other comorbidities [ 15 ]. However, because of the nonalcoholic effect in the second hit model, the results of the modelling may be different from the mechanism and pathological changes caused by alcohol alone [ 9 , 205 ].…”

“…Therefore, further rigorous research is needed to clarify the differences in the susceptibility of rodents to ALD in different environments [ 10 ]. At present, rodent ALD models are still ideal and effective tools for improving our understanding of ALD [ 205 ]. Although there are differences in the degree and stage of ALD between rodents and humans, with continuous improvements and development in ALD animal models, future models could gradually simulate each stage and the pathological characteristics of human ALD [ 9 ].…”

Unveiling the Therapeutic Potential of Vitamin-E in Preventing Inflammation and Stromal Congestion in Alcoholic Liver Injury

“…Groups B and C were administered a daily dose of 30 ml/kg/day of 30% ethanol via a pediatric nasogastric tube. Moreover, group C underwent an additional treatment regimen, wherein they were provided with vitamin E at a dosage of 50 mg/kg/day, dissolved in 2 ml of distilled water, and also administered through a nasogastric tube [ 14 , 15 ]. Each of the three groups was further segmented into two subgroups, labeled as I and II, based on the duration of the experiment: one group underwent an eight-week experimental period, while the other experienced a four-week experimental duration.…”