Efeito da exposição pré-natal ao álcool no miocárdio de camundongos C57BL/6: impactos na expressão de RNA mensageiro de componentes das vias de cinética do cálcio, inflamação, apoptose e estresse oxidativo em machos e fêmeas adultos

Abstract

Alcohol is a psychoactive substance with addictive properties that has been widely used in many cultures for centuries. The abusive use of alcohol causes a large number of illnesses, in addition to a social and economic burden on countries. Women are more vulnerable to alcohol consumption due to a lower amount of enzymes that metabolize it. Alcohol consumption during pregnancy can induce molecular, physiological and behavioral changes in the fetus, often irreversible, such as cell death and imbalance between the production of reactive oxygen species (ROS) and the ability of fetal cells to protect themselves with endogenous antioxidants . This work aimed to analyze the effect of prenatal alcohol exposure (PAE) on the myocardium of C57BL/6 mice and its impacts on messenger RNA (mRNA) expression of components of calcium kinetic pathways, inflammation, apoptosis and stress oxidative in males and females. To obtain the offspring, object of study of this project, 20 inbred mice (15 females and 5 males) of the C57Bl/6 lineage were used. Females were randomized into two groups: Control group – CT (n = 4) and prenatal alcohol exposure group – PAE (n = 11). Five males and 5 females per offspring were analyzed. Ninety days after birth (PN90), animals in both groups were anesthetized by inhalation with isoflurane (<20 seconds) and decapitated. A total of 17 genes were selected according to their participation in signal transduction pathways (VTS) of calcium kinetics, inflammation, apoptosis and oxidative stress in dysfunction cardiovascular. The differential expression of these genes was analyzed in male and female mice submitted to PAE. For statistical analysis, two-way ANOVA was performed, followed by Bonferroni's ad hoc test. We verified an increase in mRNA expression of oxidative stress genes GPX4, Cat, Hspa1a/b, Sod1 in males in the PAE group compared to the control group. There was no increase for females in the PAE group of the Cat and Hspa1a/b genes. We also observed a difference in mRNA expression between males and females in the PAE group, with a significant increase in GPX4 mRNA. Males and females in the PAE group showed an increase in mRNA expression in the IL-6, Tnfrsf1a, Tnf-α inflammation genes compared to the control group. Males showed an increase in the Tnfrsf1 gene compared to females in the PAE group. In the apoptosis genes Bax, Mapk1, Mapk14 and TP53, the PAE group showed a significant increase compared to the control group, there was no increase in the FAS gene. The PAE group showed increased Atp2a2, PLN and RYR-2 compared to the control group, while the female CAsq2 and SLC8a1as genes in the PAE group showed a decrease in mRNA expression compared to the control group. We conclude that PAE can trigger significant alterations in the expression of genes related to calcium kinetics, apoptosis and inflammation and oxidative stress in animals of both sexes. We found that males suffered a greater injury. The presence of estrogen, which attenuates the development of heart disease, may have been essential for the greater protection observed in females.