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<p>Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs’ cholestatic potential. This review outlines the main triggering mechanisms of drug-induced cholestasis and summarizes the currently available in vitro systems and techniques that attempt to forecast and provide mechanistic details of cholestasis caused by drugs.</p>

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Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月11日

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  • Enrique Timor-López,
  • Laia Tolosa,
  • M. Teresa Donato

摘要

Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs’ cholestatic potential. This review outlines the main triggering mechanisms of drug-induced cholestasis and summarizes the currently available in vitro systems and techniques that attempt to forecast and provide mechanistic details of cholestasis caused by drugs.