Role of glutathione in the susceptibility of Trypanosoma cruzi to drugs

• Published in: Comparative biochemistry and physiology. C, Comparative pharmacology Vol. 94; no. 1; pp. 87 - 91
• Main Authors: Moncada, C., Repetto, Y., Aldunate, J., Letelier, M.E., Morello, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 1989; New York, NY Pergamon Press
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimetabolites - pharmacology; Antiparasitic agents; Biological and medical sciences; Buthionine Sulfoximine; Diazooxonorleucine - pharmacology; gamma-Glutamyltransferase - antagonists & inhibitors; gamma-Glutamyltransferase - metabolism; Glutathione - biosynthesis; Glutathione - physiology; Glutathione Transferase - metabolism; Medical sciences; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - pharmacology; Nifurtimox - pharmacology; Nitrofurans - pharmacology; Nitroimidazoles - pharmacology; Pharmacology. Drug treatments; Tropical medicine; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects; Therapeutic efficiency; Protozoa; Drug combination; Tripeptide; In vitro; Trypanosoma cruzi; Sensitivity resistance; Synthesis; Epimastigote; Parasiticid; Rhizoflagellata; Inhibitor; Comparative study; Glutathione
• ISSN: 0306-4492; 0742-8413
• DOI: 10.1016/0742-8413(89)90148-5

1. Glutathione (G-SH) concentration, γ-glutamyltranspeptidase and glutathione S-transferase activities were studied in several strains of T. cruzi epimastigotes. GSH varied from li]1.04 mM for the LQ strain to 0.61 mM for the Tulahuen strain. 2. Cultures of the LQ strain presented more resistance to drugs than those of the Tulahuen. It was necessary a concentration of nifurtimox 4 times higher and one of benznidazole 10 times higher in order to inhibit approximately to 50% the growth of LQ strain cultures when compared with the Tulahuen strain. 3. Buthionine sulfoximine decreased the concentration of glutathione to about 50% in the LQ and Tulahuen strains and potentiated the toxicity of nifurtimox and benznidazole in T. cruzi epimastigote cultures. These results suggest that glutathione is an important factor in the resistance of T. cruzi to nifurtimox and benznidazole.