Document Detail

Glutathione conjugation of synthetic steroids in isolated rat hepatocytes.
MedLine Citation:
PMID:  2588308     Owner:  NLM     Status:  MEDLINE    
When designing steroid drugs with multiple double bonds, the influence of glutathione conjugation on the pharmacodynamics of drug action should be considered. We have examined the effect of canrenone, a mineralocorticoid receptor antagonist, on isolated rat hepatocytes and found that 1 mM canrenone injured the hepatocytes during shortterm incubation at 37 C, while an analogue of canrenone which bears 4 double bonds (delta 1,11-CAN) did not manifest such toxicity. To further pursue this, we prepared testosterone analogues comprising multiple double bonds as model compounds, and incubated them with freshly isolated rat hepatocytes. The viability of the hepatocytes was not influenced by any of the steroids, but some of them having a double bond at the C6-C7 position reduced the cellular glutathione levels. This was found to be due to conjugation of glutathione to the C7 position of the steroid molecule, and the rate of conjugation was accelerated when an additional double bond was introduced at C1-C2 or C11-C12 positions. The finding is interesting as glucuronidation or sulfation are common as conjugation processes of steroids.
J Higaki; T Matsui; Y Ikenishi; M Hirata
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Steroids     Volume:  54     ISSN:  0039-128X     ISO Abbreviation:  Steroids     Publication Date:  1989 Sep 
Date Detail:
Created Date:  1990-01-09     Completed Date:  1990-01-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0404536     Medline TA:  Steroids     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  345-54     Citation Subset:  IM    
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
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MeSH Terms
Canrenone / metabolism*,  pharmacology
Cell Survival / drug effects
Glutathione / metabolism*
Liver / metabolism*
Mass Spectrometry
Pregnadienes / metabolism*
Rats, Inbred Strains
Testosterone / analogs & derivatives*,  metabolism
Reg. No./Substance:
0/Pregnadienes; 58-22-0/Testosterone; 70-18-8/Glutathione; 976-71-6/Canrenone

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

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