PMID: 9551679Apr 29, 1998Paper

Rat liver transport and biotransformation of a cytostatic complex of bis-cholylglycinate and platinum (II)

Journal of Hepatology
Jose J G MarinG R Villanueva

Abstract

Bile acids have previously been used as shuttles for directing organic drugs to the liver. The aim of this study was to investigate liver transport and biotransformation of a new cytostatic bioinorganic complex (Bamet-H2), that was obtained by binding platinum(II) to two cholylglycinate moieties. Using rat hepatocytes in primary culture, the kinetics of cholylglycinate, cisplatin and Bamet-H2 uptake were studied. Sodium-dependency of Bamet-H2 uptake was investigated by replacement of 116 mM NaCl by 116 mM choline chloride. Liver biotransformation was investigated by HPLC analysis of bile samples collected from anesthetized rats following intravenous Bamet-H2 administration. Using isolated rat liver preparations, which were perfused with erythrocyte- and albumin-free Krebs-Henseleit solutions for 40 min, measurement of cholylglycinate, cisplatin and Bamet-H2 uptake and bile output was carried out. Interaction between Bamet-H2 and cholylglycinate for liver transport was studied by co-administration of 1 microM Bamet-H2 plus 500 microM cholylglycinate and 1 microM [14C]-cholylglycinate plus 500 microM Bamet-H2. Both cholylglycinate and Bamet-H2 uptake by rat hepatocytes followed saturation kinetics. Comparison between the two comp...Continue Reading

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Citations

Oct 10, 1998·International Journal of Cancer. Journal International Du Cancer·J J MarinM A Serrano
Aug 13, 2013·Chemical Reviews·Franck Le Bideau, Samuel Dagorne
Oct 26, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elina Sievänen
Jun 13, 2013·Molecular Cancer Therapeutics·Cynthia S LancasterAlex Sparreboom

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