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Effect of penicillin G on the biliary excretion of cholephilic compounds in rats.
MedLine Citation:
PMID:  21431887     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM: Penicillin G is reported to increase bile flow by increasing biliary glutathione excretion, as well as the biliary excretion of penicillin G itself. In order to study the effect of penicillin G on the hepatic excretory pathway, the effect of colchicine and genipin on the increase of biliary glutathione excretion induced by penicillin G was studied in rats. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin was also studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide. METHODS: After bile duct cannulation, penicillin G was administered to rats at the rate of 0.5 μmol/min/100 g. The effect was examined of colchicine pretreatment (0.2 mg/100 g) and genipin administration (0.5 μmol/min/100 g) on biliary glutathione excretion increased by penicillin G infused at the rate of 0.5 μmol/min/100 g. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin (0.2 and 0.1 μmol/min/100 g for 90 min, respectively) was studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide (0.075 μmol/min/100 g for 20 min). RESULTS: Penicillin G increased bile flow and biliary glutathione excretion, which were not inhibited by colchicine or genipin. Biliary penicillin G excretion was markedly reduced in Eisai hyperbilirubinemic rats (EHBR) and Mrp2-deficient rats. Biliary sulfobromophthalein and erythromycin excretion was unchanged by penicillin G. Cholestasis induced by estradiol-17β-glucuronide was not relieved by penicillin G. CONCLUSIONS: It was shown that colchicine-sensitive vesicular transport has no role on the penicillin G-induced insertion of Mrp2 into the canalicular membrane, as has been observed with genipin. Although the choleresis of penicillin G is thought to be due to the increased biliary excretion of glutathione and penicillin G itself by Mrp2, the mechanism of Mrp2 insertion by penicillin G is thought to be partly different from that by genipin.
Authors:
Masako Fukami; Atsushi Tanka; Hajime Takikawa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-24
Journal Detail:
Title:  Journal of hepato-biliary-pancreatic sciences     Volume:  -     ISSN:  1868-6982     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528587     Medline TA:  J Hepatobiliary Pancreat Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, 173-8605, Japan.
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