Allopurinol is effective to modify the evolution of Trypanosoma cruzi infection in mice.
There is a real need for new and less toxic drugs for the treatment of Chagas disease, as nifurtimox and benznidazole are effective but toxic and provoke unpleasant side effects, especially in adult patients. Allopurinol, commonly used to treat the hiperuricemia, is also used by the Trypanosoma cruzi's hypoxantine guanine fosforyltransferase as an alternative substrate incorporating it into the parasite's ribonucleic acid, provoking the death of the parasite. However, the results of using allopurinol as chemotherapy for Chagas disease are not clear. For that, we investigated the evolution of the T. cruzi infection in mice treated with allopurinol (5, 10 or 15 mg/kg for 90 days) obtaining a reduction in the parasitaemia (p<0.05), no electrocardiographic alterations (p<0.05) and a conserved myocardial and cardiac beta-receptors' affinity values with the highest dose of the drug, compared to those of the uninfected mice. Cruzipain immunoglobulin G levels remained high in all the groups as well as the survival (70%, 90 days post-infection). Allopurinol prevented the acute phase evolving into the chronic cardiac disease.
Gobbi
Paola
P
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000, Córdoba, Argentina.
Lo Presti
María S
MS
Fernández
Alicia R
AR
Enders
Julio E
JE
Fretes
Ricardo
R
Gea
Susana
S
Paglini-Oliva
Patricia A
PA
Rivarola
Héctor W
HW
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D003546:Cysteine Endopeptidases / Q000276:immunology; D004562:Electrocardiography; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia; D015800:Protozoan Proteins; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; D000493:Allopurinol; D003546:Cysteine Endopeptidases; C063214:cruzipain