The aerobic metabolism of metronidazole by Trypanosoma cruzi epimastigotes.
Trypanosoma cruzi epimastigotes actively metabolize metronidazole under aerobic conditions to a polar compound tentatively identified as 2-methyl-5-nitroimidazole-1-yl-acetic acid. The rate of metabolite formation is increased by more than 50% by pretreatment with phenobarbital and inhibited by SKF-525A and metyrapone. The reaction is dramatically stimulated by the addition of flavone which suggests that the metabolite is produced via the cytochrome P-450 system. Apparently the nitro group in the metabolite is maintained intact. Detoxication reactions catalyzed by cytochrome P-450 appear to be more important than previously suspected as a basis to explain at least partially the resistance of these organisms to known antimicrobial agents. However, other factors such as the fate of nitro substituent in metronidazole require further evaluation.
D000332:Aerobiosis; D000818:Animals; D008795:Metronidazole / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D013045:Species Specificity; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000378:metabolism*
D008795:Metronidazole; D011335:Proadifen; D010634:Phenobarbital; D008797:Metyrapone