Role of glutathione in the susceptibility of Trypanosoma cruzi to drugs.
1. Glutathione (G-SH) concentration, gamma-glutamyltranspeptidase and glutathione S-transferase activities were studied in several strains of T. cruzi epimastigotes. GSH varied from 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.
Moncada
C
C
Department of Biochemistry and Chemistry, Faculty of Medicine, University of Chile, Santiago.
Repetto
Y
Y
Aldunate
J
J
Letelier
M E
ME
Morello
A
A
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D003980:Diazooxonorleucine / Q000494:pharmacology; D005978:Glutathione / Q000096:biosynthesis / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009547:Nifurtimox / Q000494:pharmacology*; D009581:Nitrofurans / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000963:Antimetabolites; D009581:Nitrofurans; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D003980:Diazooxonorleucine; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D009547:Nifurtimox; C009999:benzonidazole