PMID: 2106446Feb 1, 1990Paper

Ultrastructural effects of Nifurtimox on rat adrenal cortex related to reductive biotransformation

Experimental and Molecular Pathology
Carmen Rodríguez de CastroJ A Castro

Abstract

Nifurtimox (Nfx) (4(5-nitrofurfurylidene)amino)-3-methylthiomorpholine-1, 1-dioxide) is a drug used against Chagas' disease, a parasitic sickness afflicting several million Latin Americans. Nfx administration to Sprague-Dawley male rats (220-250 g) at a dose of 100 mg/kg caused pronounced alterations in the adrenal cortex involving the fasciculata and reticularis zones but which were not evident in the glomerulosa. Alterations observed involved mitochondria, nuclei, Golgi apparatus, and the endoplasmic reticulum but were more intense in the mitochondria. There is Nfx nitroreductase activity in the adrenal microsomal, mitochondrial, and cytosolic-rich fractions but most of it is in the mitochondrial-rich fraction. Activity in the first two fractions requires NADPH and that in the cytosol is only observed in the presence of hypoxanthine as substrate. Enzymatic activity in all fractions is inhibited by oxygen. CO does not inhibit mitochondrial Nfx nitroreductase and inhibits only 10% of the microsomal enzyme activity. Hypoxanthine-dependent cytosolic activity is inhibited by allopurinol. Present results suggest that Nfx is activated to damage-producing reactive metabolites by nitroreductive biotransformation in rat adrenal organel...Continue Reading

References

Jan 1, 1976·Pharmacology & Therapeutics. Part B: General & Systematic Pharmacology·E R Simpson, J I Mason
Feb 1, 1961·The Journal of Biophysical and Biochemical Cytology·J H LUFT

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Citations

Apr 18, 2006·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·M J IatropoulosG M Williams
Aug 30, 2006·Human & Experimental Toxicology·José A CastroLaura C Bartel
Feb 13, 2010·Human & Experimental Toxicology·Laura Cecilia BartelJosé Alberto Castro
Nov 21, 2007·Human & Experimental Toxicology·L C BartelJ A Castro

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