Biliary excretion of taurocholate, organic anions and vinblastine in rats with α-naphthylisothiocyanate-induced cholestasis
Biliary excretion of taurocholate, organic anions and vinblastine in rats with α-naphthylisothiocyanate-induced cholestasis
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DOI：
10.1111/j.1440-1746.2005.03794.x
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发表时间：
2005-07-01
影响因子：
4.1
通讯作者：
Takikawa, H
中科院分区：
文献类型：
--
作者：
Kurihara, H;Sano, N;Takikawa, H
背景和目的：已知α-萘异硫氰酸酯（ANIT）可损伤胆管上皮细胞导致胆汁淤积。本研究的目的是研究单剂量的ANIT对胆汁排泄的各种亲胆化合物和小管transporters.Methods的量的影响：24小时后，口服ANIT（100 mg/kg），牛磺胆酸，白三烯C-4，普伐他汀和长春碱的胆汁排泄进行了研究。胆盐输出泵和多药耐药蛋白2的蛋白水平和多药耐药蛋白2在肝脏的免疫染色也examined.Results：ANIT治疗显着降低胆汁排泄的示踪量的牛磺胆酸，白三烯C-4，普伐他汀和长春碱。ANIT治疗后，胆汁中牛磺胆酸盐的最大排泄量也明显减少。ANIT治疗对胆盐输出泵和多药耐药蛋白2的蛋白水平和多药耐药蛋白2在liver.Conclusions的免疫染色没有影响：这些研究结果支持小管转运蛋白对ANIT诱导的胆汁淤积的胆汁排泄的显着损害的影响不大。(C)2005年Blackwell Publishing Asia Pty Ltd.
Background and Aims: alpha-Naphthylisothiocyanate (ANIT) is known to cause cholestasis due to injury of the bile duct epithelial cells. The aim of the present study was to examine the effect of a single dose of ANIT on the biliary excretion of various cholephilic compounds and on the amount of canalicular transporters.Methods: Twenty-four hours after the oral administration of ANIT (100 mg/kg), the biliary excretion of taurocholate, leukotriene C-4, pravastatin and vinblastine was studied. The protein levels of the bile salt export pump and multidrug resistance protein 2 and the immunostaining of multidrug resistance protein 2 in the liver were also examined.Results: The ANIT treatment markedly decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C-4, pravastatin and vinblastine. The biliary excretory maximum of taurocholate was also markedly decreased after ANIT treatment. The ANIT treatment had no effect on the protein levels of bile salt export pump and multidrug resistance protein 2 and the immunostaining of multidrug resistance protein 2 in the liver.Conclusions: These findings support canalicular transporters having little effect on the marked impairment of biliary excretion of cholephilic compounds in ANIT-induced cholestasis.(C) 2005 Blackwell Publishing Asia Pty Ltd.