کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602555 1133783 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
BSEP inhibition – In vitro screens to assess cholestatic potential of drugs
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
BSEP inhibition – In vitro screens to assess cholestatic potential of drugs
چکیده انگلیسی

Bile salt export pump (BSEP, ABC11) is a membrane protein that is localized in the cholesterol-rich canalicular membrane of hepatocytes. Its function is to eliminate unconjugated and conjugated bile acids/salts from hepatocyte into the bile. In humans there is no compensatory mechanism for the loss of this transporter. Mutations of BSEP result in a genetic disease, called progressive familial intrahepatic cholestasis type 2 (PFIC2), that is characterized with decreased biliary bile salt secretion, leading to decreased bile flow and accumulation of bile salts inside the hepatocyte, inflicting damage. BSEP inhibitor drugs produce similar bile salt retention that may lead to severe cholestasis and liver damage. Drug-induced liver injury is a relevant clinical issue, in severe cases ending in liver transplantation.Therefore, measurement of BSEP inhibition by candidate drugs has high importance in drug discovery and development. Although several methods are suitable to detect BSEP-drug interactions, due to interspecies differences in bile acid composition, differences in hepatobiliary transporter modulation, they have limitations. This review summarizes appropriate in vitro methods that could be able to predict BSEP-drug candidate interactions in humans before the start of clinical phases.


► The function of BSEP is to eliminate bile acids from hepatocyte into the bile.
► Drugs can cause drug induced liver injury (DILI) via several different and overlapping mechanisms.
► One possible cause of DILI is inhibition of BSEP.
► We summarize in vitro methods that could be able to point out BSEP-drug candidate interaction in humans.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 26, Issue 8, December 2012, Pages 1294–1299
نویسندگان
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