Stereoselective glutathione conjugation of a uricosuric diuretic.
A reduction of cellular glutathione (GSH) content was observed when isolated rat hepatocytes were incubated with a stereoisomer of a uricosuric diuretic (S-8666) at a high concentration. Subsequent studies have revealed it was due to conjugation of GSH and S-8666 (-)-enantiomer in the liver cytosol. The (+)-enantiomer strongly inhibited the conjugation reaction, therefore, GSH depletion did not take place when a racemic form of S-8666 was incubated with the liver cells. A possible chemical structure of the GSH-conjugate is tentatively proposed.
Higaki
J
J
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hirata
M
M
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004232:Diuretics; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013449:Sulfonamides / Q000378:metabolism*; D014528:Uricosuric Agents
D004232:Diuretics; D013449:Sulfonamides; D014528:Uricosuric Agents; C052960:S 8666; D005978:Glutathione