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Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi.
Antimicrob Agents Chemother. 2005 Jan; 49(1):126-30.AA

Abstract

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 to 9.0 muM, and decreased that of benznidazole from 43.6 to 24.1 muM. The survival of epimastigotes or trypomastigotes treated with nifurtimox or benznidazole, as measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction, was significantly decreased by 500 muM BSO. In Vero cells infected with amastigotes, 25 muM BSO was able to potentiate the effect of nifurtimox and benznidazole as measured by the percentage of infected Vero cells multiplied by the average number of intracellular amastigotes (endocytic index). At 0.5 muM nifurtimox, the proportion of Vero cells infected decreased from 27 to 20% and the endocytic index decreased from 2,500 to 980 when 25 muM BSO was added. Similar results were obtained with benznidazole- and BSO-benznidazole-treated cells. This study indicates that potentiation of nifurtimox or benznidazole by BSO could decrease the clinical dose of both drugs and diminish the side effects or the length of therapy.

Authors+Show Affiliations

University of Chile, Faculty of Medicine, Molecular and Clinical Pharmacology Program, P.O. Box 70000, Santiago 7, Chile.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15616285

Citation

Faundez, Mario, et al. "Buthionine Sulfoximine Increases the Toxicity of Nifurtimox and Benznidazole to Trypanosoma Cruzi." Antimicrobial Agents and Chemotherapy, vol. 49, no. 1, 2005, pp. 126-30.
Faundez M, Pino L, Letelier P, et al. Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. Antimicrob Agents Chemother. 2005;49(1):126-30.
Faundez, M., Pino, L., Letelier, P., Ortiz, C., López, R., Seguel, C., Ferreira, J., Pavani, M., Morello, A., & Maya, J. D. (2005). Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. Antimicrobial Agents and Chemotherapy, 49(1), 126-30.
Faundez M, et al. Buthionine Sulfoximine Increases the Toxicity of Nifurtimox and Benznidazole to Trypanosoma Cruzi. Antimicrob Agents Chemother. 2005;49(1):126-30. PubMed PMID: 15616285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. AU - Faundez,Mario, AU - Pino,Laura, AU - Letelier,Paula, AU - Ortiz,Carla, AU - López,Rodrigo, AU - Seguel,Claudia, AU - Ferreira,Jorge, AU - Pavani,Mario, AU - Morello,Antonio, AU - Maya,Juan Diego, PY - 2004/12/24/pubmed PY - 2005/2/23/medline PY - 2004/12/24/entrez SP - 126 EP - 30 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 49 IS - 1 N2 - 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 to 9.0 muM, and decreased that of benznidazole from 43.6 to 24.1 muM. The survival of epimastigotes or trypomastigotes treated with nifurtimox or benznidazole, as measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction, was significantly decreased by 500 muM BSO. In Vero cells infected with amastigotes, 25 muM BSO was able to potentiate the effect of nifurtimox and benznidazole as measured by the percentage of infected Vero cells multiplied by the average number of intracellular amastigotes (endocytic index). At 0.5 muM nifurtimox, the proportion of Vero cells infected decreased from 27 to 20% and the endocytic index decreased from 2,500 to 980 when 25 muM BSO was added. Similar results were obtained with benznidazole- and BSO-benznidazole-treated cells. This study indicates that potentiation of nifurtimox or benznidazole by BSO could decrease the clinical dose of both drugs and diminish the side effects or the length of therapy. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/15616285/Buthionine_sulfoximine_increases_the_toxicity_of_nifurtimox_and_benznidazole_to_Trypanosoma_cruzi_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=15616285 DB - PRIME DP - Unbound Medicine ER -