Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.

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Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.

Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas' disease, decreased metallothion...

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Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi.

l-Buthionine (S,R)-sulfoximine (BSO) increased the toxicity of nifurtimox and benznidazole toward the epimastigote, trypomastigote, and amastigote forms of Trypanosoma cruzi. BSO at 500 muM decreased total glutathione-derived thiols by 70 to 80% in 48 h. In epimastigotes, 500 muM BSO decreased the concentration of nifurtimox needed to inhibit constant growth of the parasites by 50%, from 14.0 t...

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INTRODUCTION The current chemotherapy for Chagas disease is unsatisfactory with only two drugs available for treatment. Research to discover new drugs for Chagas disease is urgent. Hexadecyl-phosphocholine (HPC, miltefosine) has been demonstrated to have in vitro activity against Trypanosoma cruzi parasites, but its activity on different Colombian T. cruzi strains is not known. OBJECTIVE To e...

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Nifurtimox chemotherapy: collateral effects in treated Trypanosoma cruzi infected patients.

Nifurtimox, is a nitrofuran compound with a trypanocidal effect against both trypomastigote and amastigote forms of T. cruzi. Its antiparasitic activity is due to the formation of toxic derivatives of oxygen when nifurtimox is reduced. T. cruzi presents low levels of reduced glutathione and lacks catalase and glutathione peroxi-dase, which makes the parasite very sensitive to hydrogen perox-ide...

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Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activit...

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ژورنال

عنوان ژورنال: Biological Research

سال: 2004

ISSN: 0716-9760

DOI: 10.4067/s0716-97602004000100007