HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Macias, R. I. R. Articles by Marin, J. J. G. Search for Related Content PubMed PubMed Citation Articles by Macias, R. I. R. Articles by Marin, J. J. G. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 39, 1792-1798, September 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Transport and biotransformation of the new cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) by the rat liver

Correspondence to: Jose J. G. Marin.

Rat liver uptake and bile output of the cytostatic complex cis -diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) were studied. Up to 100 µM, Bamet-R2 uptake by rat hepatocytes in primary culture followed saturation kinetics (V_max = 0.65 ± 0.12 nmol/5 min per mg protein; K_M = 45.2 ± 10.7 µM). Bamet-R2 uptake was lower than that of cholylglycinate (CG) but higher than that of cisplatin. Replacement of 116 mM NaCl by 116 mM choline chloride did not significantly reduce Bamet-R2 uptake. Addition of 500 µM CG, cholic acid, estrone sulfate, or ouabain to 50 µM Bamet-R2-containing incubation media inhibited Bamet-R2 uptake. No liver biotransformation of Bamet-R2 occurred, as indicated by HPLC analysis of bile collected from anesthetized rats after intravenous administration of the drug. Bamet-R2 uptake and secretion into bile by isolated rat livers exceeded those of cisplatin but were lower than those of CG. Differences between Bamet-R2 and CG were more marked for bile output than for liver uptake. Thus, higher Bamet-R2 than CG or cisplatin liver content was found. Co-administration of Bamet-R2 and CG revealed that CG induced a slight reduction in Bamet-R2 uptake and a marked inhibition in Bamet-R2 bile output. By contrast, Bamet-R2 had no effect on CG on either liver uptake or bile output.

In sum, the present data indicate that Bamet-R2 is efficiently taken up and secreted into bile by the rat liver by mechanisms shared in part by natural bile acids.—Macias, R. I. R., M. J. Monte, M. Y. El-Mir, G. R. Villanueva, and J. J. G. Marin. Transport and biotransformation of the new cytostatic complex cis -diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) by the rat liver. J. Lipid Res. 1998. 39: 1792–1798.

Supplementary key words: bile acid, cancer, chemotherapy, cisplatin, glycocholate, metal, platinum (Pt)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. Monte, M. R. Ballestero, O. Briz, M. J. Perez, and J. J. G. Marin Proapoptotic Effect on Normal and Tumor Intestinal Cells of Cytostatic Drugs with Enterohepatic Organotropism J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 24 - 35. [Abstract] [Full Text] [PDF]

				O. Briz, R. I. R. Macias, M. Vallejo, A. Silva, M. A. Serrano, and J. J. G. Marin Usefulness of Liposomes Loaded with Cytostatic Bile Acid Derivatives to Circumvent Chemotherapy Resistance of Enterohepatic Tumors Mol. Pharmacol., March 1, 2003; 63(3): 742 - 750. [Abstract] [Full Text] [PDF]

				O. Briz, M. A. Serrano, N. Rebollo, B. Hagenbuch, P. J. Meier, H. Koepsell, and J. J.G. Marin Carriers Involved in Targeting the Cytostatic Bile Acid-Cisplatin Derivatives cis-Diammine-chloro-cholylglycinate-platinum(II) and cis-Diammine-bisursodeoxycholate-platinum(II) toward Liver Cells Mol. Pharmacol., April 1, 2002; 61(4): 853 - 860. [Abstract] [Full Text] [PDF]

				M. F. Dominguez, R. I. R. Macias, I. Izco-Basurko, A. de la Fuente, M. J. Pascual, J. M. Criado, M. J. Monte, J. Yajeya, and J. J. G. Marin Low in Vivo Toxicity of a Novel Cisplatin-Ursodeoxycholic Derivative (Bamet-UD2) with Enhanced Cytostatic Activity versus Liver Tumors J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1106 - 1112. [Abstract] [Full Text]