The analysis selleck chemical Baricitinib of organ weight revealed that although parasite infection induced an increase in all studied organs (heart, spleen, liver and kidney), only statistically significant differences were observed in liver weight (p=0.022) from infected and untreated mice as compared to uninfected animal groups (data not shown). As compared to untreated mice, all treated groups �C Bz (p=0.029), DB1965 (p=0.013) and Bz+DB 1965 (p=0.022) lead to a return of heart weight to pre-infection values (data not shown). Regarding liver, only the combined therapy partially restored (p=0.03) the organ weight increase due to parasite infection (data not shown). ECG analysis showed a statistically significant bradycardia (p=0.02) in infected and untreated mice group as already reported in this experimental model of acute T.

cruzi infection [21]. However, none of the therapeutic groups were able to avoid this cardiac electric alteration (data not shown). No statistically significant differences were found in blood pressure analysis among all studied groups (data not shown). Also, among all treatment regimens, only 1 out of 06 surviving mice from the DB1965 treated groups (12.5 mg dose �C scheme 1 and DB1965+Bz �C scheme 3) displayed negative hemocultive. However, both animals displayed positive PCR, showing no parasitological cure (Table 4). Histopathology analysis revealed that no major differences could be found in the cardiac tissues among the different experimental infected mice groups (data not shown).

Aiming to explore the potential cumulative toxicity after a long-term treatment, different clinical and biochemical parameters were evaluated after 20 daily consecutive doses of each compound. Our data showed that all groups presented 100% survival, and that except for the analysis of body weight (variation between mouse groups measured after the end of the treatment), no major toxic side effects could be observed. We found that mice injected with vehicle alone reached 49��11% of body weight gain, while Bz-treated animals showed 25��11% significant decrease (p=0.006) (data not shown). Discussion AIAs belong to a class of amidine compounds with high trypanocidal activity in vitro [14] and in vivo [11] and the present study confirmed and extended previous observations of their properties. The evaluation of both in vitro and in vivo effects of DB1831/DB1965 against T.

cruzi infection showed their excellent efficacy against bloodstream trypomastigotes and intracellular amastigotes, with high selectivity indexes, confirming previous data using Drug_discovery other AIAs [11], [12], [14]. DB1831 exhibited an outstanding effect against intracellular parasites (IC50=5 nM), which is about 560-fold higher than Bz. The high activity of DB1831 and DB1965 was maintained when BT were incubated at different temperatures and with blood mice, also confirming the promising activity of AIAs for a blood decontamination protocol [11], [14].