Animals Models of Gastrointestinal and Liver Diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges

Abstract

Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

Consumo De Álcool E a Influência Do Exercício Físico Na Atividade Enzimática De Ratos Wistar

“…Diversos autores 3,6,7,10,11 tentam demonstrar os mecanismos envolvidos na injuria hepática causada pelo álcool que corroboram para a elevação plasmática das aminotransferases. O etanol é oxidado no fíga-do até a forma de acetaldeído, que em excesso compromete a função de organelas dos hepatócitos, em especial as mitocôndrias.…”

“…Doenças pulmonares 5 , cardíacas e cerebrovasculares, eventos fatais e transtornos psiquiátricos 6 , traumas 7 , várias neoplasias 8 , doenças sexualmente transmissíveis 9 e o desenvolvimento de doenças no fígado decorrente da ingestão alcoólica são as principais alterações fisiológicas descritas devido ao abuso de álcool 10 . Em humanos, assim como em animais, as doenças hepáticas associadas podem abranger quadros como esteatose, cirrose e carcinoma hepatocelular 11,12 .…”

“…As atividades enzimáti-cas plasmáticas da AST, ALT, ALP, amilase e GGT foram determinadas por métodos cinéticos específicos utilizando-se conjuntos diagnósticos comerciais BioSystems ® (BioSystems, Curitiba, Paraná, Brasil Em relação a experimentação animal, o tamanho mínimo da amostra foi definida de acordo com uma variância estimada previamente descritos na literatura 10 . A fórmula proposta por Callegari-Jacques e Cochran foi utilizado para o cálculo.…”

Role of phosphodiesterase-4 in alcohol-induced organ injury.

“…Significantly, there are pathogenic changes in the gut barrier function leading to increased intestinal permeability and systemic endotoxemia and inflammation in the Lieber De Carli alcohol feeding model [179]. Hence, this model of chronic alcohol feeding was utilized in the present study to examine the link between alcohol-induced systemic endotoxemia and development of brain inflammation [219,220]. Indeed, results of our study showed that alcohol feeding significantly increased endotoxin levels.…”

“…The Lieber De Carli diet that we used was a very useful tool to simulate the American diet and human chronic alcohol drinking [220,234]. Rodents are given 5% of ethanol in the liquid diet, which is similar to a strong beer.…”