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. Author manuscript; available in PMC: 2015 Nov 1.
Published in final edited form as: Clin Pharmacol Ther. 2014 Jul 28;96(5):589–598. doi: 10.1038/clpt.2014.158

Figure 1. Mechanism of troglitazone (TGZ) hepatotoxicity.

Figure 1

Bile acids are taken up into the hepatocytes primarily by sodium-taurocholate cotransporting polypeptide (NTCP) and also by organic anion transporting polypeptides (OATPs). Hepatocellular bile acids are excreted into bile primarily via the bile salt export pump (BSEP). Bile acids also can be transported across the basolateral membrane to sinusoidal blood via basolateral efflux transporters such as multidrug resistance-associated protein (MRP)4, MRP3, and/or organic solute transporter (OST)α/β. TGZ and its major metabolite, TGZ sulfate (TS), are potent inhibitors of hepatic bile acid transporters, which might lead to hepatic bile acid accumulation and subsequent toxicity.