Dados do Trabalho

Título

Intraperitoneal Administration of 17-DMAG, a Hsp90 Inhibitor, as an Effective Treatment Against Leishmania braziliensis Infection in BALB/c Mice

Introdução

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa. Current treatments have limitations, necessitating the development of new therapeutic interventions. Previous studies showed the leishmanicidal effects of Hsp90 inhibitors, including 17-DMAG. This study evaluates the efficacy of intraperitoneal 17-DMAG in controlling L. braziliensis infection.

Objetivo (s)

To assess the efficacy of intraperitoneal 17-DMAG in controlling L. braziliensis infection in vivo.

Material e Métodos

BALB/c mice were infected with L. braziliensis promastigotes. After two weeks, mice were intraperitoneally treated with 17-DMAG at different doses (20 mg/kg daily, 30 mg/kg every two days, or 50 mg/kg every five days) to determine the optimal protocol. Subsequent assays involved daily treatment with the effective dose (20 mg/kg daily) or a glucose control for varying durations. Lesion size, lymph node size, histopathological findings, parasite burden, and cytokine production were evaluated. Parasite persistence after treatment cessation and lesion development was also assessed.

Resultados e Conclusão

RESULTS: Treatment with 17-DMAG (20 mg/kg/daily) reduced lymph node and lesion size after two, four, and seven weeks (reduction of 6, 7, and 500 times). Additionally, the treatment led to decreased production of proinflammatory cytokines IL-6 (three times), TNF (seven times), and IFN (36 times). Inflammatory infiltrate was also decreased at the lesion site after 7 days. After four weeks, ear parasite burden was reduced by 250 times, and complete clearance of parasite burden was achieved in the lymph nodes. Following four weeks of treatment cessation, the ear of the treated group exhibited a persistent parasite burden similar to that observed at the end of treatment, while the control group showed no parasites. However, in the lymph nodes, the parasite burden was found to be 36 times lower in the treated group compared to the control group. When treatment was initiated five weeks after infection, both groups showed complete elimination of parasites in the ear, while only the treated group demonstrated parasite clearance in the lymph nodes. In contrast, the control group exhibited persistent parasites with a burden 550 times greater than the treated group. CONCLUSION: Intraperitoneal 17-DMAG exhibits potent anti-leishmanial effects against L. braziliensis in vivo.

Palavras-chave

Leishmaniasis; Leishmania braziliensis; 17-DMAG; Hsp90; Treatment.

Agradecimentos

IGM (Fiocruz BA); PgBSMI; CAPES; CNPq; FAPESB; INOVA; Innovative products, 2nd round.