Sulphoxide 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 rabbit tissues. Sulindac reduction was about 10-fold higher in homogenates of rat kidney and liver than in other tissues although the tissue differences decreased when dithiothreitol was used as a co-factor. The greatest sulindac reducing activity in rat liver was in the cytosolic fraction whereas reoxidation of the thioether back to the sulphoxide was largely in the microsomal fraction. Studies using NADPH/NADH, acetaldehyde and dithiothreitol as cofactors showed that aldehyde oxidase was the main sulindac reducing system in rat and rabbit liver cytosols but not in renal cytosols where reduction was probably linked to the thioredoxin system, as reported previously. Menadione and hydralazine caused essentially complete inhibition of sulindac reduction by hepatic but not renal cytosol and the inhibition was dependent on preincubation of the enzyme with the inhibitor, which is indicative of aldehyde oxidase activity. Little reduction of sulphinpyrazone or diphenyl sulphoxide was detected with rat or rabbit kidney or renal cytosols, although increased reduction was detected when acetaldehyde was added as a cofactor to rabbit and rat liver cytosols. The data indicate that different enzyme systems are responsible for sulphoxide reduction in the liver and kidney.
Lee
S C
SC
University of Southampton, U.K.
Renwick
A G
AG
D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011817:Rabbits; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013442:Sulfinpyrazone / Q000378:metabolism; D013467:Sulindac / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology
D001555:Benzene Derivatives; D014812:Vitamin K; D013467:Sulindac; D006830:Hydralazine; C048860:diphenyl sulfoxide; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C030542:sulfoxide reductase; D013442:Sulfinpyrazone