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

摘要

Cardiac muscle is characterized by an adverse structural remodeling when damaged, which inducescardiac insufficiency, deregulation of homeostasis and death. Agents that could attenuate these effects, such asmelatonin (ME), have been proposed as potential cardio-protectors. To evaluate this possibility, most of thestudies focus on acute heart damage treatments, giving less attention to schemes associated to repetitive events ofheart injury. The aim of our study was to evaluate the effect of melatonin on the heart of young male micetreated with repeated administrations of isoproterenol (ISO), a β-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 myocardialnitrotyrosine (3-NT) were quantified. Our results show that VH, CF, CI and 3-NT were no different between SSand ME-groups. VH in ISO and ME/ISO-groups was 15.07 and 12.72% higher than in SS, respectively. InME/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, butalways above SS (p<0.001). These results suggest that melatonin could attenuate heart injury by modifyingimportant processes involved in cardiac remodeling, such as fibrosis, inflammation and oxidative stress as isdemonstrated in the present study by the decrements in CF, CI and 3-NT. Studies comparing the effect ofantioxidant, antifibrotic and anti-inflammatory agents should provide evidences with regard to the mechanismsof action of melatonin.