Avaliação do efeito protetor da melatonina exógena sobre os neonatos de matrizes submetidas ao consumo crônico de álcool durante a prenhez

Abstract

Alcohol consumption during pregnancy is a serious public health problem because it increases the risk of spontaneous abortions, mental retardation and congenital anomalies, compromising healthy fetal development. Production of acetaldehyde and increase in the liberation of free radicals due to the metabolism of ethanol are the main factors that contribute to the damages induced by alcohol. These products react and injure proteins, lipids and DNA of the cells and thus impair organogenesis and fetal physiology. Melatonin is a powerful antioxidant capable of freely crossing the morphological and physiological barriers found in cells and cell compartments, including the nucleus and mitochondria, protecting cell membranes, proteins and nuclear and mitochondrial genomes. The objective of this study was to evaluate the protective effect of exogenous melatonin on the neonates of matrices submitted to chronic alcohol consumption during pregnancy. Twenty pregnant rats were used and divided into the groups: I - Rats receiving distilled water (control); II - Rats receiving absolute ethyl alcohol (3 g/kg/day); III - Rats receiving absolute ethyl alcohol (3 g/kg/day) and melatonin (10 mg/kg/day); IV - Rats receiving absolute ethyl alcohol (3 g/kg/day) and melatonin (15 mg/kg/day). After birth, dams and 10 neonates (five males and five females) of each experimental group were anesthetized to collect of the dams' blood and liver and of the neonates' blood, liver and brain to verify the frequency of DNA damage by the comet assay. Blood was also used for the micronucleus test. Analyzes of size and birth weight of newborns, as well as, morphometric, histochemical (quantification of glycogen and collagen) and immunohistochemical (tumor necrosis factor alpha - TNF-α and interleukin 6 - IL-6) evaluations in the liver of these animals were also performed. Our results demonstrated a significant increase in DNA damage in the blood and liver cells of the dams and offspring of the alcohol group as well as in the brains of these neonates. Treatments with melatonin (10 and 15 mg/kg/day) significantly reduced the genotoxicity caused by ethanol in the blood of dams and neonates (males and females), liver of dams and male offspring, and in the brain of offspring of females. It was also shown that only the offspring of females exposed to maternal alcohol consumption showed a higher frequency of micronuclei in polychromatic erythrocytes. In addition, intrauterine exposure to alcohol resulted in a significant reduction in neonatal length and birth weight. Moreover, it reduced the number of hepatocytes and their nuclear area, increased the cytoplasmic area of these cells, decreased the accumulation of hepatic glycogen and raised the levels of the proinflammatory cytokines TNF-α and IL-6. However, the number of megakaryocytes and collagen deposition were not altered. Treatments with melatonin at 10 and 15 mg/kg during pregnancy protected the neonates against injuries caused by maternal alcohol consumption on growth, birth weight and hepatic morphophysiology. Thus, we conclude that treatment with exogenous melatonin may be an effective strategy in protecting against damage induced by intrauterine exposure to alcohol.