Abstract
Several β-lactam antibiotics, especially those containing N-methyl- tetrazolylthiomethyl groups at the 3-position of the cephalosporin nucleus, affect the alcohol-metabolizing system in rats. These effects were compared those with disulfiram, well-known as a potent inhibitor of aldehyde dehydrogenase (ALDH). Both disulfiram and antibiotics containing the N-methyltetrazolylthiome- thyl group inhibited both mitochondrial low Km ALDH and acetaldehyde oxidation in rat livers. The high Km ALDH and alcohol dehydrogenase activities in livers were not affected by these treatments. When ethanol was given to rats pretreated with disulfiram or these antibiotics, the blood acetaldehyde concentration increased markedly concomitant with a decrease in activity of the low Km ALDH. Administration of N-methyltetrazolethiol alone suppressed the low Km enzyme activity and also increased the blood acetaldehyde level; both effects were pronounced and observed several hours after administration. β-Lactam antibiotics without N-methyltetrazolethiol in their molecule did not affect the liver mitochondrial enzyme activity or the blood acetaldehyde level.
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