Dados do Trabalho

Título

Effects of treatment with the association of benznidazole with ICM20a on infection chronic murine with the Colombian strain of Trypanosoma cruzi

Objetivo(s)

To evaluate the effects of treatment with the association of benznidazole (BZ) and ICM-20a in mice inoculated with Trypanosoma cruzi during the chronic phase of the infection

Material e Métodos

Balb/c mice were divided into the following groups: 1) Uninfected and untreated (NI); 2) Infected and untreated (NT); 3) Infected and treated with BZ 100 mg/kg/day; 4) Infected and treated with ICM20a; 5) Infected and treated with ICM20a + BZ 5 mg/kg/day. The animals were inoculated intraperitoneally with 500 blood trypomastigotes of the Colombian strain of T. cruzi, considered drug resistant, and submitted to a fresh blood test. At 60 days after inoculation (dpi) no parasites were observed in the blood, characterizing the chronic phase of the experimental infection, and treatments were started for 20 consecutive days. The blood, heart and skeletal muscle (SM) of the animals were submitted to evaluations by qPCR and the heart and SM to immunomodulatory evaluation, with dosage of pro-inflammatory cytokines (IL-6, TNF-α, INF-γ, IL-2 and IL-17) and anti-inflammatory (IL-4, IL-10)

Resultados e Conclusão

Treatment with ICM20a promoted a reduction (p≤0.0001) of the parasite load (PC) detected by qPCR in blood and cardiac tissue compared to NT animals and animals treated with BZ 100 mg. Treatment with ICM20a+BZ 5 mg promoted a reduction (p≤0.0001) of CP in the three types of tissue in relation to NT animals, and in blood and heart in relation to those treated with BZ 100 mg. Treatment with ICM20a+BZ 5 mg eliminated the parasite DNA from the MS and heart, and almost completely from the blood. NT animals showed higher levels (p≤0.0001) of IL-6, TNF-α and IFN-γ compared to NI, and those treated with 100 mg BZ and ICM20a showed a reduction (p≤0.0001) in the levels of these cytokines compared to NT. The animals treated with ICM20a+BZ 5 mg showed a reduction (p≤0.0001) in the levels of pro-inflammatory cytokines compared to NT, and values similar to those of NI animals. Treatment with ICM20a+BZ 5 mg showed anti-T. cruzi similar to treatment with BZ 100 mg but without the inflammatory response induced by the latter. The treatments evaluated promoted a reduction in CP without resulting in a parasitological cure. However, the combination ICM20a+BZ 5 mg promoted a greater reduction in CP and in the three different tissues, requiring further investigations into the use of this association, as a potential alternative treatment for Chagas disease.

Palavras-chave

mice, Trypanosoma cruzi, drug association, chronic phase