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.