Benznidazole and nifurtimox nitroreductase activity in liver microsomes from male rats preinduced with phenobarbital or 3-methylcholanthrene
- PMID: 3841223
Benznidazole and nifurtimox nitroreductase activity in liver microsomes from male rats preinduced with phenobarbital or 3-methylcholanthrene
Abstract
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.
Similar articles
-
Species and sex differences in the liver microsomal nitroreductive biotransformation of nifurtimox and benznidazole.Arch Int Pharmacodyn Ther. 1987 Jun;287(2):181-7. Arch Int Pharmacodyn Ther. 1987. PMID: 3632141
-
Liver microsomal benznidazole and nifurtimox nitroreductase activity in male rats of different age.Arch Int Pharmacodyn Ther. 1987 Sep;289(1):11-7. Arch Int Pharmacodyn Ther. 1987. PMID: 3435199
-
Nitroreduction of benznidazole and nifurtimox by rat and human feces.Res Commun Chem Pathol Pharmacol. 1983 Aug;41(2):341-4. Res Commun Chem Pathol Pharmacol. 1983. PMID: 6688884
-
Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease).Biomed Environ Sci. 1988 Jun;1(1):19-33. Biomed Environ Sci. 1988. PMID: 3151755 Review.
-
Free radical metabolism of antiparasitic agents.Fed Proc. 1986 Sep;45(10):2471-6. Fed Proc. 1986. PMID: 3017765 Review.
Cited by
-
Interaction of benznidazole reactive metabolites with nuclear and kinetoplastic DNA, proteins and lipids from Trypanosoma cruzi.Experientia. 1988 Oct 15;44(10):880-1. doi: 10.1007/BF01941187. Experientia. 1988. PMID: 3053234
-
Evidence for hydroxyl free radical formation during paraquat but not for nifurtimox liver microsomal biotransformation. A dimethyl-sulfoxide scavenging study.Arch Toxicol. 1988;62(5):355-8. doi: 10.1007/BF00293623. Arch Toxicol. 1988. PMID: 3242445
-
Regulation of biotransformation systems and ABC transporters by benznidazole in HepG2 cells: involvement of pregnane X-receptor.PLoS Negl Trop Dis. 2012;6(12):e1951. doi: 10.1371/journal.pntd.0001951. Epub 2012 Dec 13. PLoS Negl Trop Dis. 2012. PMID: 23272261 Free PMC article.