Metronidazole (Flagyl), lactate and ethanol: enhancement of cytotoxic action and the effect of a dehydrogenase inhibitor and a drug metabolite.
The cytotoxicity of metronidazole towards CHO cells in culture has been found to be enhanced by the presence of lactate and ethanol. For 20 mM lactate the maximum enhancement was observed with 5 mM metronidazole. The enhancement by lactate was reduced by the additional presence of 5 mM oxamate (an LDH inhibitor) and 5 mM hydroxyethyl oxamate (a metronidazole metabolite). The cytotoxicity of 5 mM metronidazole was also enhanced by the presence of 30 mM ethanol. The results suggest an involvement of dehydrogenase enzyme systems in the hypoxic activation and toxicity of some nitroimidazoles.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008795:Metronidazole / Q000494:pharmacology*; D010053:Ovary; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D007773:Lactates; D008795:Metronidazole; D019344:Lactic Acid; D000431:Ethanol; C029371:hydroxyethyloxamic acid; D007770:L-Lactate Dehydrogenase; D010072:Oxamic Acid