Decrements in fibrosis, cell infiltrates and oxidative stress, but not in ventricular hypertrophy by melatonin in isoproterenol-induced heart injury of mice

Cardiac muscle is characterized by an adverse structural remodeling when damaged, which induces cardiac insufficiency, deregulation of homeostasis and death. Agents that could attenuate these effects, such as melatonin (ME), have been proposed as potential cardio-protectors. To evaluate this possibility, most of the studies focus on acute heart damage treatments, giving less attention to schemes associated to repetitive events of heart injury. The aim of our study was to evaluate the effect of melatonin on the heart of young male mice treated with repeated administrations of isoproterenol (ISO), a-adrenergic agonist. One control (saline solution (SS)) and three experimental groups (ISO, ME and ME/ISO) were considered. Ventricular hypertrophy (VH), proportion of myocardial collagen fibers (CF) and cell infiltrates (CI), as well as detection of myocardial nitrotyrosine (3-NT) were quantified. Our results show that VH, CF, CI and 3-NT were no different between SS and ME-groups. VH in ISO and ME/ISO-groups was 15.07 and 12.72% higher than in SS, respectively. In ME/ISO-group, CF, CI and 3-NT were 78.74 +/- 0.45, 61.87 +/- 2.45 and 75.48 +/- 0.70% lower than in ISO-group, but always above SS (p< 0.001). These results suggest that melatonin could attenuate heart injury by modifying important processes involved in cardiac remodeling, such as fibrosis, inflammation and oxidative stress as is demonstrated in the present study by the decrements in CF, CI and 3-NT. Studies comparing the effect of antioxidant, antifibrotic and anti-inflammatory agents should provide evidences with regard to the mechanisms of action of melatonin.