Trypanosoma cruzi: in vitro and in vivo antiproliferative effects of epigallocatechin gallate (EGCg).
The trypanocidal activity of catechins on Trypanosoma cruzi bloodstream trypomastigotes has been previously reported. Herein, we present the effect of epigallocatechin gallate (EGCg) on parasitemia and survival in a murine model of acute Chagas' disease as well as on the epimastigote form of the parasite. Upon intraperitoneal administration of daily doses of 0.8 mg/kg/day of EGCg for 45 days, mice survival rates increased from 11% to 60%, while parasitemia diminished to 50%. No side effects were observed in EGCg-treated animals. Fifty percent inhibition of epimastigotes growth was achieved with 311 microM EGCg 120 h after drug addition. No lysis, total culture growth inhibition or morphological changes were observed upon addition of 1-3mM EGCg at 24 h. This treatment also produced oligosomal fragmentation of epimastigotes DNA, suggesting a programmed cell death (PCD)-like process. All these findings point out EGCg as a potential new lead compound for chemotherapy of Chagas' disease.
Güida
María C
MC
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular y Facultad de Ciencias Exactas y Naturales (CONICET-UBA), 1428 Buenos Aires, Argentina. mcguida@dna.uba.ar
Esteva
Mónica I
MI
Camino
Alejandra
A
Flawiá
Mirtha M
MM
Torres
Héctor N
HN
Paveto
Cristina
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D011897:Random Allocation; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
D000975:Antioxidants; D014344:Trypanocidal Agents; D002392:Catechin; C045651:epigallocatechin gallate