Efeito da melatonina em células mononucleares do sangue materno e da placenta de mães diabéticas

Abstract

Diabetes mellitus is a heterogeneous group of metabolic disorders that presents in common the hyperglycemia that when associated with gestation can cause several complications for both mother and fetus. Diabetic pregnant women are at higher risk of complications associated with placenta.During pregnancy, maternal hyperglycemia can alter cellular oxidative metabolism at the maternal-fetal interface leading to oxidative stress with imbalance in the formation of reactive oxygen species (ROS) and antioxidant defense. Studies report the effects of the hormone melatonin on the pro and antioxidant mechanisms of cells, but the effects of this hormone on mononuclear (MN) cells of maternal blood and placenta of diabetic mothers are still partially understood.Thus, the objective of this study was to evaluate in pregnancies complicated by diabetes mellitus, oxidative stress and the induction of apoptosis in maternal blood mononuclear cells and placental cells modulated by melatonin.A total of 40 pregnant women were included in the groups: non-diabetic (ND, N = 20) and type 2 diabetes mellitus (DM2, N = 20). Blood and placenta cells were obtained by density gradient and maintained in culture for 24 hours in a hothouse (5% CO2), in the presence or absence of melatonin (100 ng / mL). Oxidative stress was evaluated by the release of the superoxide anion and by the determination of CuZn superoxide dismutase (SOD) in the culture supernatant. Apoptosis was assessed by flow cytometry. Maternal hyperglycemia was observed to increase superoxide release, reduced SOD concentration and SOD / O2- ratio and increased apoptosis in MN cells from maternal blood. Melatonin was able to reduce oxidative stress and apoptosis rates in MN cells in the maternal blood of diabetic mothers. In the maternal layer of placenta (extravilosa) there was reduction of SOD and SOD / O2- ratio and melatonin restored the concentrations of this enzyme. There was greater release of superoxide, reduction of the SOD / O2 ratio. and apoptosis in MN cells of the fetal (villous) layer of the placenta of hyperglycemic mothers. Melatonin was able to act on placental tissue cells by increasing apoptosis rates in the villous layer of the placenta of hyperglycemic mothers. These data suggest that hyperglycemia was able to alter the balance between superoxide anion production and the enzyme superoxide dismutase SOD) in maternal blood and in the placenta of diabetic mothers. These changes reflected in the mechanisms of induction of apoptosis and were modulated by the melatonin hormone. It is possible that this hormone acts in this process favoring the maintenance and development of the fetus in pregnancies of diabetic mothers.