Melatonin and dehydroepiandrosterone combination: does this treatment exert a synergistic effect during experimental Trypanosoma cruzi infection?

• Published in: Journal of pineal research 2009-10, Vol.47 (3), p.253-259
• Main Authors: Kuehn, Christian C., Rodrigues Oliveira, Luiz G., Santos, Carla Domingues, Ferreira, Daniele Silva, Alonso Toldo, Míriam P., De Albuquerque, Sérgio, Do Prado Jr, José Clóvis
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - therapeutic use; Animals; Antioxidants - therapeutic use; Biological and medical sciences; Chagas Disease - drug therapy; dehydroepiandrosterone; Dehydroepiandrosterone - therapeutic use; Drug Combinations; Drug Synergism; Fundamental and applied biological sciences. Psychology; Human protozoal diseases; Infectious diseases; Macrophages - drug effects; Macrophages - metabolism; Male; Medical sciences; melatonin; Melatonin - therapeutic use; nitric oxide; parasitemia; Parasitemia - drug therapy; Parasitic diseases; Protozoal diseases; Rats; Rats, Wistar; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosomiasis; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: endocrinology
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.2009.00708.x

:  Previous studies showed that melatonin or dehydroepiandrosterone (DHEA) enhances the immune response against parasitic pathogens. The present study investigated the in vitro activity of melatonin combined with DHEA in a period of 24 hr during the course of in vivo T. cruzi infection. The in vitro activity of melatonin or DHEA alone, as well as together, were tested for the trypomastigote forms (doses ranging from 0.5 to 128 μm). In vitro, neither melatonin nor DHEA alone had any activity against trypomastigote forms, although when the highest concentration of combined melatonin and DHEA was used, it was active against the trypomastigote forms of the parasite. However, for this concentration, a quite toxicity on peritoneal macrophages was observed. For in vivo evaluation, male Wistar rats were infected with the Y strain of T. cruzi. They were orally treated with 10 mg/kg body weight/day of melatonin and subcutaneously with 40 mg/kg body weight/day of DHEA. Treatment with melatonin, DHEA and the association showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection as compared to untreated animals (P