Document Detail


Formation, toxicity and inactivation of acrolein during biotransformation of cyclophosphamide as studied in freshly isolated cells from rat liver and kidney.
MedLine Citation:
PMID:  4026579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study the formation and the effects of cyclophosphamide-derived acrolein were investigated using isolated cells from rat liver and kidney, with particular regard to the protective action of low molecular weight thiols against cellular toxicity. The results may be summarized as follows: Cyclophosphamide (CTX)-mediated toxicity to isolated cells is dependent on cytochrome P-450 activity; Loss of viability in cells incubated with cyclophosphamide is preceded by a depletion of cellular GSH; Stimulation of cellular GSH synthesis or the presence of low molecular weight thiols in the incubation medium protects against cyclophosphamide-induced toxicity; Acrolein is probably formed extracellularly as well as intracellularly and can be detoxified by thiol compounds, forming a thiochemiacetal or a thioether.
Authors:
Y Ohno; K Ormstad
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of toxicology     Volume:  57     ISSN:  0340-5761     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  1985 Jun 
Date Detail:
Created Date:  1985-09-19     Completed Date:  1985-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  99-103     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acrolein / metabolism*,  toxicity
Aldehydes / metabolism*
Animals
Biotransformation
Chromatography, High Pressure Liquid
Cyclophosphamide / metabolism*,  toxicity
Glutathione / metabolism
Kidney / cytology,  metabolism*
Kinetics
Liver / cytology,  metabolism*
Male
Metabolic Detoxication, Drug
Metyrapone / pharmacology
Phenobarbital / pharmacology
Rats
Rats, Inbred Strains
Sulfhydryl Compounds / pharmacology
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Sulfhydryl Compounds; 107-02-8/Acrolein; 50-06-6/Phenobarbital; 50-18-0/Cyclophosphamide; 54-36-4/Metyrapone; 70-18-8/Glutathione

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


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