Establishment of an easy-to-construct liver injury mouse model for longitudinal analysis by drinking-water administration of MDA

Abstract

AbstractCompound actions are diverse, capable of inducing various biological responses, making them a valuable exploratory tool for understanding biological mechanisms. While widely employed in liver dysfunction research, models requiring continuous administration for longitudinal studies come with high construction costs. Although drinking water models are useful, currently utilized compounds are limited, with thioacetamide being one of the few examples. Is it possible to expand drinking water models for liver dysfunction research? Addressing this question, our study focused on constructing a novel drinking water-induced liver injury model. Through data mining and literature research, 4,4’-methylenedianiline (MDA) was identified, whose drinking water administration consistently exhibited elevated ALT levels over 28 days. To evaluate differences in pathophysiological profiles compared to existing thioacetamide models, we acquired multi-view data of early biochemical test values, immune cell trafficking, and transcriptome over time. The analysis revealed unique features such as elevated total bilirubin in serum, increased monocyte-derived macrophages in the liver, and enhanced fibrinolysis in the liver, suggesting a model of cholestatic liver injury. This study proposes the first cholestatic liver injury model for compound drinking water administration, expanding the scope of longitudinal analysis in liver dysfunction research.