Linked Life Data

2588308

Source:http://linkedlifedata.com/resource/pubmed/id/2588308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1990-1-9
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-54
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Glutathione conjugation of synthetic steroids in isolated rat hepatocytes.
pubmed:affiliation
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
pubmed:publicationType
Journal Article, In Vitro