Metabolism in vitro of sulindac. Sulfoxide-reducing enzyme systems in guinea pig liver.
The sulfoxide reduction of sulindac (cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl)-benzylidenyl]indene-3-acetic acid), an anti-inflammatory agent, was demonstrated in vitro by cell-free preparations of guinea pig liver. The sulfoxide reductase activity was located in both fractions of microsomes and 105000X g supernatant. The microsomal reductase was NADPH- or NADH-dependent, and required the factor present in the soluble fraction for its activity. The factor was heat-labile and non-dialyzable. Furthermore, a partial purification of the microsomal NADPH-cytochrome c reductase resulted in a paralleled increase of the sulfoxide reductase activity. The present observations suggest that the soluble factor described above functions as an electron transfer component coupled with NADPH-cytochrome c reductase.
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007192:Indenes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D013454:Sulfoxides / Q000378:metabolism; D013467:Sulindac / Q000378:metabolism*
D007192:Indenes; D013454:Sulfoxides; D013467:Sulindac; D002248:Carbon Monoxide; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase