Abstract
S-Methyl N, N-diethylthiolcarbamate sulfone (DETC-Me sulfone) was investigated for its rat liver mitochondrial low K m aldehyde dehydrogenase (ALDH 2) inhibitory properties. DETC-Me sulfone inhibited ALDH 2 in vitro ( ic 50 = 3.8 μ M ) and in vivo ( id 50 = 170 μ mol/kg; 31 mg/kg ). Maximum inhibition (60%) of ALDH 2 was observed 8 hr after DETC-Me sulfone administration. In addition, incubation of S-methyl N, N-diethylthiolcarbamate (DETC-Me) or S-methyl N, N-diethylthiolcarbamate sulfoxide (DETC-Me sulfoxide) with rat liver microsomes and an NADPH-generating system failed to produce DETC-Me sulfone. Furthermore, DETC-Me sulfone could not be detected in plasma from rats treated with either DETC-Me sulfoxide or DETC-Me sulfone. In conclusion, DETC-Me sulfone inhibited ALDH 2 in vitro and in vivo. However, there was no evidence suggesting that DETC-Me sulfoxide was metabolized to DETC-Me sulfone.
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