Protective actions of melatonin against heart damage during chronic Chagas disease.
Chronic cardiomyopathy is the most important clinical form of Chagas disease, and it is characterised by myocarditis that is associated with fibrosis and organ dysfunction. Alternative treatment options are important tools to modulate host immune responses. The main goal of this work was to evaluate the anti-inflammatory actions of melatonin during the chronic phase of Chagas disease. TNF-α, IL-10 and nitrite concentrations were evaluated as predictive factors of immune modulation. Creatine phosphokinase-MB (CK-MB), cardiac inflammatory foci and heart weight were assessed to evaluate the efficacy of the melatonin treatment. Male Wistar rats were infected with 1×10(5) blood trypomastigotes of the Y strain of Trypanosoma cruzi and kept untreated for 60 days to mimic chronic infection. After this period, the rats were orally treated with melatonin 50mg/kg/day, and the experiments were performed 90, 120, and 180 days post-infection. Melatonin treatment significantly increased the concentration of IL-10 and reduced the concentrations of NO and TNF-α produced by cardiomyocytes. Furthermore, it led to decreased heart weight, serum CK-MB levels and inflammatory foci when compared to the untreated and infected control groups. We conclude that melatonin therapy is effective at protecting animals against the harmful cardiac inflammatory response that is characteristic of chronic T. cruzi infection.
Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto FCFRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: lgustavo@fcfrp.usp.br.
Luiz Gustavo Rodrigues
LG
Oliveira
Christian Collins
CC
Kuehn
Carla Domingues
CD
dos Santos
Mariza Abreu
MA
Miranda
Cassia Mariana Bronzon
CM
da Costa
Vagner José
VJ
Mendonça
José Clóvis
JC
do Prado Júnior
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002598:Chagas Cardiomyopathy / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology*; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000254:growth & development
D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D016207:Cytokines; D009569:Nitric Oxide; D008550:Melatonin
CK-MB; IL-10; Melatonin; Nitric oxide; TNF-α; Trypanosoma cruzi