Biliary excretion of taurocholate, organic anions and vinblastine in rats with alpha-naphthylisothiocyanate-induced cholestasis.

Abstract

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.

• Authors: Hiroko Kurihara, Naoyo Sano, Hajime Takikawa
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 20 Issue 7 Pg. 1069-74 (Jul 2005) ISSN: 0815-9319 [Print] Australia
• PMID: 15955216 (Publication Type: Comparative Study, Journal Article)
• Copyright: (c) 2005 Blackwell Publishing Asia Pty Ltd.

Chemical References

• Anions
• Antineoplastic Agents, Phytogenic
• Bile Acids and Salts
• Cholagogues and Choleretics
• 1-Naphthylisothiocyanate
• Taurocholic Acid
• Vinblastine

Topics

• 1-Naphthylisothiocyanate (administration & dosage, toxicity)
• Administration, Oral
• Animals
• Anions
• Antineoplastic Agents, Phytogenic (pharmacokinetics)
• Bile (metabolism)
• Bile Acids and Salts (metabolism)
• Biological Transport (drug effects)
• Cholagogues and Choleretics (pharmacokinetics)
• Cholestasis (chemically induced, metabolism)
• Disease Models, Animal
• Male
• Rats
• Rats, Sprague-Dawley
• Taurocholic Acid (pharmacokinetics)
• Vinblastine (pharmacokinetics)