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  • Title: Effects of cephem antibiotics on rat liver aldehyde dehydrogenases.
    Author: Yamanaka Y, Yamamoto T, Egashira T.
    Journal: Jpn J Pharmacol; 1983 Aug; 33(4):717-23. PubMed ID: 6632378.
    Abstract:
    Effects of cephem antibiotics, 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 greater than LMOX greater than CPZ. Disulfiram inhibited the enzyme activity by 50% at approx. 40 microM. The antibiotics (except CTM) at a dose of 1,000 mg/kg i.v. inhibited the low-Km ALDH activity by 36-52% of the control 24 hr after pretreatment, but did not alter the high-Km ALDH activity. The degrees of inhibition were in the order: LMOX = CMD greater than CPZ greater than CMZ. Disulfiram at a dose of 300 mg/kg p.o. 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 hr at a dose of 1,000 mg/kg i.v. The degrees of elevation at 1 hr after ethanol injection were in the order: LMOX greater than CMD greater than CPZ greater than CMZ. The present experiments demonstrated that the rise in blood acetaldehyde levels coincided with the inhibition rates of the low-Km ALDH activity by the cephem antibiotics.
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