Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is a drug used against Chagas' disease, a parasitic disease afflicting several millions of Latin Americans. Bz administration to Sprague-Dawley male rats at 100 mg/kg p.o. caused subcellular alterations in the adrenal cortex involving fasciculata and reticularis zones but not in the glomerulosa. There is Bz nitroreductase activity in the adrenal microsomal and mitochondrial fractions but most of it is localized in mitochondria. Activity in the two fractions requires NADPH under anaerobic conditions. Mitochondrial Bz nitroreductase activity was inhibited by oxygen. A minor but statistically significant inhibition was observed in mixtures incubated under carbon monoxide. Microsomal Bz nitroreductase activity was not detected under oxygen atmosphere and was not inhibited under carbon monoxide. No Bz nitroreductase activity mediated by xanthine oxidase or aldehyde oxidase was detected in the cytosolic fraction from rat adrenals. Electron microscopic examination of the adrenal cortex from Bz-treated animals revealed cells with marked lipid accumulation and alterations in nuclei, endoplasmic reticulum and mitochondria in the reticularis and fasciculata zones. In vitro results suggest a Bz nitroreductive activation, with minor or null P-450 participation, leading to reactive metabolites able to cause damage in various organelles.
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PMID:Benznidazole-induced ultrastructural alterations in rat adrenal cortex. Mechanistic studies. 151 44

Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole-acetamide) is a drug used against Chagas' disease. Rat liver microsomal and cytosolic fractions, but not mitochondria, exhibited Bz nitroreductase activity under anaerobic conditions in the presence of NADPH. Microsomal nitroreductase activity was enhanced by FAD and was inhibited totally by oxygen and partially by carbon monoxide. Liver cystosol fraction was able to reduce Bz nitrogroups in the presence of either N-methylnicotinamide or hypoxanthine as substrates. These enzyme activities were inhibited by menadione or allopurinol respectively. Under every experimental condition leading to enzymatic reduction of Bz nitrogroups and its inhibition or enhancement, reactive metabolites that bind covalently to proteins were also produced. This covalent binding was effectively prevented by reduced glutathione. Results suggest the participation of cytochrome P-450 and cytochrome c reductase in liver microsomal processes and of xanthine oxidase and aldehyde oxidase in liver cytosolic processes of Bz nitroreduction and activation to reactive metabolites that bind covalently to proteins. Possible pharmacological and toxicological implications of the described observations were discussed.
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PMID:Reductive metabolism and activation of benznidazole. 671 14

Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas' disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4+/-4.0 and 149.2+/-14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.
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PMID:Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus. 1296 22