Biliary excretion of taurocholate, organic anions and vinblastine in rats with alpha-naphthylisothiocyanate-induced cholestasis.
OBJECTIVE
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.
Kurihara
Hiroko
H
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Sano
Naoyo
N
Takikawa
Hajime
H
D015058:1-Naphthylisothiocyanate / Q000008:administration & dosage / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D000838:Anions; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000493:pharmacokinetics*; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000493:pharmacokinetics*; D014747:Vinblastine / Q000493:pharmacokinetics*
D000838:Anions; D000972:Antineoplastic Agents, Phytogenic; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D015058:1-Naphthylisothiocyanate; D013656:Taurocholic Acid; D014747:Vinblastine