Document Detail


Cellular pharmacology of liposomal cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum (II) in mouse resident peritoneal macrophages, Kupffer cells, and hepatocytes.
MedLine Citation:
PMID:  3342409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The in vitro and in vivo interaction of liposomal cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ + (II) (L-NDDP) with mouse resident peritoneal macrophages (RPM), Kupffer cells (KC), and hepatocytes was studied. The peak in vitro uptake of L-NDDP by RPM was 12.5 ng elemental platinum/100 micrograms cell protein and constituted 0.2% of the platinum available for phagocytosis. The subsequent release of platinum by RPM was rapid initially, with a 20-fold increase over the first 4 h, followed by a plateau; ultrafilterable (free) platinum constituted 50% of the total platinum released at 24 h. The retained intracellular platinum in RPM at 24 h was close to 50% of that initially present. The peak in vitro uptake of L-NDDP by KC was 11.3 ng platinum/100 micrograms cell protein and amounted to 0.2% of the platinum available for phagocytosis. The release of platinum by KC was detectable only after 4 h of incubation and increased 3-fold over the next 14 h. The ultrafilterable platinum released by KC at 18 h was 40% of the total platinum released. The retained intracellular platinum in KC at 18 h was 33% of that initially present. The peak in vitro uptake of L-NDDP by hepatocytes was almost 50 ng platinum/100 micrograms cell protein and constituted 0.8% of the platinum available for intake. Following the i.v. injection of L-NDDP, hepatocytes contained up to 6-fold higher platinum concentrations than KC. This observation was supported by transmission electron microscopy showing a higher concentration of multilamellar vesicles within hepatocytes than in KC, 5 min after i.v. injection of L-NDDP. These findings suggest that L-NDDP becomes available to the liver following i.v. injection, that both macrophages and hepatocytes play a role in the metabolism of L-NDDP, and that Kupffer cells could mediate a sustained release of platinum in the liver following the interaction with L-NDDP, indicating the potential of L-NDDP for the treatment of tumors in the liver.
Authors:
J Lautersztain; R Perez-Soler; J Turpin; A R Khokhar; Z H Siddik; K Schmidt; G Lopez-Berestein
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  48     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1988 Mar 
Date Detail:
Created Date:  1988-03-28     Completed Date:  1988-03-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1300-6     Citation Subset:  IM    
Affiliation:
Department of Clinical Immunology and Biological Therapy, University of Texas M. D. Anderson Hospital and Tumor Institute, Houston 77030-2603.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / administration & dosage,  pharmacokinetics*
Kupffer Cells / metabolism*
Liposomes / administration & dosage*
Liver / metabolism*,  ultrastructure
Macrophages / metabolism*
Male
Mice
Organoplatinum Compounds / pharmacokinetics*
Platinum / pharmacokinetics
Grant Support
ID/Acronym/Agency:
CA41581/CA/NCI NIH HHS; RR5511-23/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Liposomes; 0/Organoplatinum Compounds; 113427-19-3/bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II); 7440-06-4/Platinum

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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