Biliary excretion of taurocholate, organic anions and vinblastine in rats with α‐naphthylisothiocyanate‐induced cholestasis

Abstract

These findings support canalicular transporters having little effect on the marked impairment of biliary excretion of cholephilic compounds in ANIT-induced cholestasis.

Bile Acids Metabonomic Study on the CCl4- and α-Naphthylisothiocyanate-Induced Animal Models: Quantitative Analysis of 22 Bile Acids by Ultraperformance Liquid Chromatography−Mass Spectrometry

“…However, ANIT is known to cause cholestasis due to injury of the bile duct epithelial cells. In CCl 4 -induced hepatic injury rats, the patho- logical changes indicated liver cell degeneration and necrosis, while ANIT-induced hepatic injury was characterized by cholangiolitic hepatitis and acute cholestasis (14,16,21). Our metabonomics analysis was just correlated with the different hepatotoxic mechanisms of CCl 4 and ANIT.…”

Large dose means significant effect – dose and effect relationship of Chi-Dan-Tui-Huang decoction on alpha-naphthylisothiocyanate-induced cholestatic hepatitis in rats

“…ANIT is a hepatotoxican widely used in rodents to imitate human intrahepatic cholestasis over the years [ 30 ]. Furthermore, ANIT induced hepatotoxicity animal model is considered to be useful for evaluating the therapeutic effect of medicines [ 31 , 32 ].In this research, the relationship between the dose of CDTHD and protective effects was investigated under ANIT induced cholestatic hepatitis. We firstly performed a subacute toxicity study of CDTHD.…”

In Silico Prediction of Biliary Excretion of Drugs in Rats Based on Physicochemical Properties

“…When the same computational model was applied to 25 structurally diverse compounds whose rat biliary excretion data were published by different laboratories (Hirom et al, 1972b;Russell and Klaassen 1973;Fahrig et al, 1989;Monsarrat et al, 1990;Masuda et al, 1997;Hinchman et al, 1998;Payan et al, 1999;Song et al, 1999;Arimori et al, 2003;Chong et al, 2003;Funakoshi et al, 2003;Moriwaki et al, 2003;Kamath et al, 2005aKamath et al, ,b, 2008Kurihara et al, 2005;Takayanagi et al, 2005;Akashi et al, 2006;Beconi et al, 2007), the predicted and observed biliary excretion values were again very close for most compounds. The clear exceptions were cephradine and paclitaxel (Monsarrat et al, 1990;Moriwaki et al, 2003).…”

“…For example, pravastatin and losoxantrone were found to be mainly eliminated as intact parent through biliary excretion in humans (Hatanaka 2000;Joshi et al, 2001). In rats, pravastatin and methotrexate were minimally metabolized and were primarily excreted intact into bile (Masuda et al, 1997;Kurihara et al, 2005). Extensive biliary excretion can be linked to a high clearance (Arimori et al, 2003), enterohepatic recirculation (Caldwell and Cline 1976;Rollins and Klaassen 1979), toxic gastrointestinal side effects (Kato et al, 2002), and potential drug-drug interactions (Luo et al, 2007).…”