Sulfoxides as urinary metabolites of S-allyl-L-cysteine in rats: evidence for the involvement of flavin-containing monooxygenases.
S-Allyl-L-cysteine (SAC), a component of garlic and a metabolite of allyl halides, is a known substrate for multiple flavin-containing monooxygenases (FMOs). In the current study, we characterize the in vivo SAC metabolism by investigating the presence of SAC, N-acetyl-S-allyl-L-cysteine (NASAC), and their corresponding sulfoxides in the urine of rats given SAC (200 or 400 mg/kg i.p.). In some experiments, rats were given aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate beta-lyase, or methimazole, an alternative FMO substrate, 30 min prior to treatment with 200 mg/kg SAC. Nearly 40 to 50% of the dose was recovered in the 24-h collection period. In all treatment groups, the majority of the metabolites were excreted within 8 h. The major metabolites detected were NASAC and NASAC sulfoxide (NASACS; nearly 30-40% and 5-10% of the dose, respectively). Only small amounts of the dose (approximately 1.5%) were recovered as SAC and SAC sulfoxide (SACS). Methimazole pretreatment significantly reduced amounts of both SACS and NASACS detected in the urine when compared with rats given SAC only, whereas AOAA pretreatment had no effect. In vitro assays using rat liver microsomes were also carried out to compare the sulfoxidation rates of SAC and NASAC. The results showed that SAC was much more readily oxidized than NASAC. Collectively, the results provide evidence for the involvement of FMOs in the in vivo metabolism of SAC and that SAC is a much better substrate for FMOs than its corresponding mercapturic acid.
Krause
Renee J
RJ
Department of Comparative Biosciences and the Center for Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Glocke
Steven C
SC
Elfarra
Adnan A
AA
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides / Q000378:metabolism / Q000652:urine*
D013454:Sulfoxides; C065299:S-allylcysteine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D003545:Cysteine