Benznidazole and nifurtimox nitroreductase activity in liver microsomes from male rats preinduced with phenobarbital or 3-methylcholanthrene.
Liver microsomes from Sprague-Dawley male rats are able to biotransform Benznidazole (Bz) or Nifurtimox (NFX) by nitroreduction. Pretreatment of the rats during three days with phenobarbital (80 mg/kg/day, ip) but not with 3-methylcholanthrene (35 mg/kg/day ip) increased both Bz and NFX nitroreductase activity. Results suggest that cytochrome P-450 but not cytochrome P-448 is involved in the nitroreduction of these two chemotherapeutic agents against Chagas' disease. Possible pharmacological and toxicological implications of these observations are discussed.
D000818:Animals; D001711:Biotransformation; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009547:Nifurtimox / Q000378:metabolism*; D009581:Nitrofurans / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D009601:Nitroreductases; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009581:Nitrofurans; D009593:Nitroimidazoles; D008748:Methylcholanthrene; D010088:Oxidoreductases; D009601:Nitroreductases; D009547:Nifurtimox; C009999:benzonidazole; D010634:Phenobarbital