Current Models for Predicting Drug-induced Cholestasis: The Role of Hepatobiliary Transport System

AuthorFarahnaz Jazaerien
AuthorMohammad Sheibanien
AuthorSadaf Nezamoleslamien
AuthorLeila Moezien
AuthorAhmad-Reza Dehpouren
Issued Date2021-04-30en
AbstractDrug-induced cholestasis is the main type of liver disorder accompanied by high morbidity and mortality. Evidence for the role of hepatobiliary pumps in the cholestasis patho-mechanism is constantly increasing. Recognition of the interactions of chemical agents with these transporters at the initial phases of drug discovery can help develop new drug candidates with low cholestasis potential. This review delivers an outline of the role of these transport proteins in bile creation. It addresses the pathophysiological mechanism for drug-induced cholestasis. In-vitro models, including cell-based and membrane-based approaches and In-vivo models such as genetic knockout animals, are considered. The benefits and restrictions of each model are discussed in this review. Current understandings into the cellular and molecular process that control the activity of hepatobiliary pumps have directed to a better understanding of the pathophysiology of drug-induced cholestasis. A combination of in-vitro monitoring for transport interaction, in-silico predicting systems, and consideration of and metabolic and physicochemical properties must cause more effective monitoring of possible liver problems.en
DOIhttps://doi.org/10.22037/ijpr.2020.113362.14254en
KeywordDrugen
KeywordCholestasisen
KeywordIn-vivoen
KeywordIn-vitroen
KeywordModelsen
KeywordTransport systemen
PublisherBrieflandsen
TitleCurrent Models for Predicting Drug-induced Cholestasis: The Role of Hepatobiliary Transport Systemen
TypeReview Article_importeden

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