Sulfoxide reduction. In vitro reduction of sulindac by rat hepatic cytosolic enzymes.

The reductive biotransformation of sulindac to the corresponding sulfide has been characterized in vitro in rat preparations with respect to subcellular and tissue distribution, cofactor requirements, kinetic constants, and the effects of inhibitors. The highest activity was found in hepatic and renal cytosolic fractions. Either NADPH or dithiothreitol effectively supported the reaction but NADH was much less effective. The KM and Vmax for sulindac were found to be 36.7 +/- 3.8 microM and 75.7 +/- 9.7 pmol/min/mg of protein, respectively, and the KM and Vmax for NADPH were found to be 0.48 +/- 0.03 microM and 43.3 +/- 4.6 pmol/min/mg of protein, respectively. The most effective inhibitors of the reaction were sulfhydryl reagents and sulfoxides structurally related to sulindac.