ASSESSMENT OF BENZNIDAZOLE AND CCR4 ANTAGONIST COMBINATION FOR Trypanosoma cruzi CHRONIC INFECTION TREATMENT

ESTEFANÍA PROCHETTO; IVÁN BONTEMPI; MIGUEL VICCO; LUZ RODELES; GABRIEL CABRERA; JAGADEESH BAYRY; GIULIANA LUPI; CAROLINA ROLDAN; LIHUE GONZALEZ; LUZ PEVERENGO; IVÁN MARCIPAR

Ciudad Autónoma de Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

SAP

Benznidazole (Bz) is the main drug used to treat T. cruzi infection. Besides itsparasiticide effect it is able to stimulate T cell specific effector responses.Taking in mind that this immunological modulation has shown to be importantfor parasite eradication, in this work we hypothesized that the efficacy of Bztreatment could be improved by inhibiting T regulatory cells, using a CCR4antagonist receptor (CCR4a). BALB/c mice were infected with 10 6trypomastigotes of Sylvio T. cruzi strain. Treatment was administered at 120days post infection (dpi) and groups were assigned as follow: CCR4a+Bz(treated with subcutaneous CCR4a and oral administration of Bz 100 mg/kg);CCR4a alone; Bz alone (100 mg/kg); PBS (untreated infected group) and NI(non-infected group). At 188 and 273 dpi, parasitemia was evaluated byqualitative PCR. Also, specific IgG1 and IgG2a levels were measured byindirect ELISA. At 273 dpi, electrocardiograms (ECG) were carried out andheart parasite load was determined by PCR real time. In all infected groups, thepresence of the parasite was found before and after different treatments. Heartparasite load at day 273 was not significantly different in all infected groups.Levels of specific antibodies were meaningfully increased in all groups aftertreatment (p <0.05), being IgG2a levels higher than IgG1 levels in all cases (p<0.05). IgG2a levels decreased in CCR4a+Bz in relation to the PBS group (p<0.05). NI mice did not present electrical disturbances in ECG. In the sameway, CCR4a+Bz group demonstrated a trend to a lower frecuency ofarrhythmias comparing to PBS (p = 0.059). Otherwise, groups with CCR4a andBz alone did not decrease these alterations. Our results suggest a possiblesynergy of both drugs although it would be necessary to enlarge the groups tocorroborate these findings.