Effects of cephem antibiotics on rat liver aldehyde dehydrogenases.

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Abstract
Effects of cephem antibiotics [active against Enterobacter, Proteus and Pseudomonas aeruginosa], which have a tetrazolethiol side chain, on rat liver mitochondrial aldehyde dehydrogenases (ALDH) were investigated in vitro and in vivo. The antibiotics tested were cefmetazole (CMZ), cefamandole (CMD), cefotiam (CTM), cefoperazone (CPZ) and latamoxef (LMOX). The antibiotics inhibited low-Km ALDH activity by 17-30% at 5 mM in vitro. The degrees of inhibition were in the order: CMZ = CTM = CMD > LMOX > CPZ. Disulfiram inhibited the enzyme activity by 50% at approximately 40 .mu.M. The antibiotics (except CTM) at a dose of 1000 mg/kg i.v. inhibited the low-Km ALDH activity by 36-52% of the control 24 h after pretreatment, but did not alter the high-Km ALDH activity. The degrees of inhibition were in the order: LMOX = CMD > CPZ > CMZ. Disulfiram at a dose of 300 m/gkg p.o. [orally] markedly inhibited the low-Km ALDH activity, but did not alter the high-Km ALDH activity. The blood acetaldehyde levels during ethanol metabolism were elevated 1.3-2.6 times in rats treated with the cephem antibiotics (except CTM) for 24 h at a dose of 1000 mg/kg i.v. The degrees of elevation at 1 h after ethanol injection were in the order: LMOX > CMD > CPZ > CMZ. The rise in blood acetaldehyde levels coincided with the inhibition rates of the low-Km ALDH activity by the cephem antibiotics.