SULFOXIDE REDUCTION BY RAT AND RABBIT-TISSUES IN-VITRO

The reduction of sulindac, sulphinpyrazone and diphenyl sulphoxide to their thioether analogues has been studied in vitro using rat and rabb it tissues. Sulindac reduction was about 10-fold higher in homogenates of rat kidney and liver than in other tissues although the tissue dif ferences decreased when dithiothreitol was used as a co-factor. The gr eatest sulindac reducing activity in rat liver was in the cytosolic fr action whereas reoxidation of the thioether back to the sulphoxide was largely in the microsomal fraction. Studies using NADPH/NADH, acetald ehyde and dithiothreitol as cofactors showed that aldehyde oxidase was the main sulindac reducing system in rat and rabbit liver cytosols bu t not in renal cytosols where reduction was probably linked to the thi oredoxin system, as reported previously, Menadione and hydralazine cau sed essentially complete inhibition of sulindac reduction by hepatic b ut not renal cytosol and the inhibition was dependent on preincubation of the enzyme with the inhibitor, which is indicative of aldehyde oxi dase activity. Little reduction of sulphinpyrazone or diphenyl sulphox ide was detected with rat or rabbit kidney or renal cytosols, although increased reduction was detected when acetaldehyde was added as a cof actor to rabbit and rat liver cytosols. The data indicate that differe nt enzyme systems are responsible for sulphoxide reduction in the live r and kidney.