دورية أكاديمية
Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport
| العنوان: | Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport |
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| المؤلفون: | Wolf, Kristina K., Vora, Sapana, Webster, Lindsey O., Generaux, Grant T., Polli, Joseph W., Brouwer, Kim L.R. |
| المصدر: | Toxicology in Vitro - An International Journal Published in Association with BIBRA, 24(1) |
| سنة النشر: | 2010 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | lactate dehydrogenase, biliary excretion index, BEIbiliary excretion index, High-throughput screening, in vitro biliary clearance, Taurocholate, SCHsandwich-cultured hepatocytes, in vitro Clbiliaryin vitro biliary clearance, Sandwich-cultured hepatocytes, In vitro models, LDHlactate dehydrogenase, DILIdrug-induced liver injury, Hanks’ balanced salts solution, HBSSHanks’ balanced salts solution, Hepatotoxicity, drug-induced liver injury, Hepatobiliary transport |
| الوصف: | Hepatocellular accumulation of bile acids due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) is one proposed mechanism of drug-induced liver injury (DILI). Some hepatotoxic compounds also are potent inhibitors of bile acid uptake by Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1). This study used a cassette dosing approach in rat and human sandwich-cultured hepatocytes (SCH) to determine whether known or suspected hepatotoxic drugs inhibit bile acid transport individually or in combination. [3H]-Taurocholate served as the NTCP/BSEP probe substrate. Individually, cyclosporin A and rifampin decreased taurocholate in vitro biliary clearance (Clbiliary) and biliary excretion index (BEI) by more than 20% in rat SCH, suggesting that these drugs primarily inhibited canalicular efflux. In contrast, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, carbamazepine, pioglitazone, and troglitazone decreased the in vitro Clbiliary by more than 20% with no notable change in BEI, suggesting that these drugs primarily inhibited taurocholate uptake. Cassette dosing (n=2–4 compounds per cassette) in rat SCH yielded similar findings, and results in human SCH were consistent with rat SCH. In summary, cassette dosing in SCH is a useful in vitro approach to identify compounds that inhibit the hepatic uptake and/or excretion of bile acids, which may cause DILI. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/3yv9-0837Test; https://cdr.lib.unc.edu/downloads/0c483s87d?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/0c483s87dTest |
| DOI: | 10.17615/3yv9-0837 |
| الإتاحة: | https://doi.org/10.17615/3yv9-0837Test https://cdr.lib.unc.edu/downloads/0c483s87d?file=thumbnailTest https://cdr.lib.unc.edu/downloads/0c483s87dTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.EE0FA148 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/3yv9-0837 |
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