Novartis Pharma AG, Preclinical Safety, Discovery and Investigative Safety, Basel, Switzerland.
Drug Safety and Epidemiology, Novartis Pharma AG, Basel, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Clin Res Hepatol Gastroenterol. 2016 Jun;40(3):257-266. doi: 10.1016/j.clinre.2015.12.017. Epub 2016 Feb 10.
Bile acid research has gained great momentum since the role of bile acids as key signaling molecules in the enterohepatic circulation was discovered. Their physiological function in regulating their own homeostasis, as well as energy and lipid metabolism make them interesting targets for the pharmaceutical industry in the context of diseases such as bile acid induced diarrhea, bile acid induced cholestasis or nonalcoholic steatohepatitis. Changes in bile acid homeostasis are also linked to various types of drug-induced liver injury (DILI). However, the key question whether bile acids are surrogate markers for monitoring DILI or key pathogenic players in the onset and progression of DILI is under intense investigation. The purpose of this review is to summarize the different facets of bile acids in the context of normal physiology, hereditary defects of bile acid transport and DILI.
自发现胆汁酸作为肠肝循环中关键信号分子的作用以来,胆汁酸研究取得了巨大进展。它们在调节自身内稳态以及能量和脂质代谢方面的生理功能,使它们成为制药行业在胆汁酸诱导性腹泻、胆汁酸诱导性胆汁淤积或非酒精性脂肪性肝炎等疾病领域的有趣靶点。胆汁酸内稳态的变化也与各种类型的药物性肝损伤(DILI)有关。然而,胆汁酸是否是监测 DILI 的替代标志物还是 DILI 发生和进展的关键致病因素这一关键问题仍在深入研究中。本文综述了胆汁酸在正常生理学、胆汁酸转运遗传性缺陷和 DILI 中的不同方面。