EVALUATION OF POSSIBLE SINERGYSM BETWEEN MELATONIN AND MELOXICAM IN THE ACUTE PHASE OF EXPERIMENTAL CHAGAS DISEASE

AC38

Luiz Gustavo Rodrigues Oliveira(1), Christian Collins Kuehn(2), Carla Domingues Dos Santos(2), Miriam Paula Alonso Toldo(2), José Clóvis do Prado Júnior (3).

Laboratório de Parasitologia, Departamento de Análises Clínicas, Bromatológicas e Toxicológica, Faculdade de Ciências Farmacêutica de Ribeirão Preto – USP

Introduction: Modulation of immune responses by administration of pharmacological active substances in models experimentally infected with Trypanosoma cruzi were hardly contributed in  the  research of new therapies against Chagas’disease. Due immunossupressor characteristics of the acute phase of the disease, the pharmacological interventions on in vivo models capable of modulate the immune system through Th-1 cytokine production are exhaustedly studied, been also relevant the effects of E2 prostaglandin synthesis blocker in the acute phase of  Chagas’disease. Objectives: To evaluate a possible synergic and immunomodulatory effects subsequent to the administration of Meloxican and Melatonin through stimulation of Th-1 cytokines production, increase of the nitric oxide production, and E2 Prostaglangin synthesis block, verifying the impact of treatment on parasitemic blood of male Wistar rats infected by  Trypanosoma cruzi Y strain. Methods: Five male Wistar rats by group weighting 90-100g  being divided into: (IWT) – Infected without treatment; IT (Mel) – Infected Treated with Melatonin; IT (Mx) – Infected Treated with Meloxican, IT (Mel + MX) – Infected Treated with Melatonin and Meloxican. After infection    with 1 x 10⁵ Y strain blood forms of T.cruzi groups were treated only in the morning with an oral solution of the substance diluted in 400 Polietilenoglycol, and distilled water (1:1 proportion). Experiments were accomplished in the 7^th, 14^th, and 21^st days after infection being the parasitemy peak determined by Brener method. Animals were killed by decapitation post anesthesia. Nitric oxide was quantified by means after the peritoneal washed cells recovering, and cytokines were measured after serum extract by specific Immunological kits (R&D Systems). Results: We could observe the increase of I FN-γ and IL-2 levels also a parasitemic decrease in experimental infected groups. Animals presented an increase of NO production which could be explained by the probable modulation of the immune systems of experimental groups treated mainly with the drugs combination in relation to TH1 cytokines production. Conclusion: The results suggested a synergic effect of the studied substances which could contribute to establish alternative treatment mechanisms by a better understanding of the immune responses against T.cruzi acute infection.