Pro-oxidant/pro-inflammatory alterations in the offspring´s heart of mild diabetic rats are regulated by maternal treatments with a mitochondrial antioxidant

Maternal diabetes programs metabolic and cardiovascular diseases in the offspring. Here, we demonstrated increased pro-oxidant/pro-inflammatory markers in the heart of 2-day-old offspring of diabetic rats, previous to the induction of metabolic alterations. At a pre-pubertal stage, sex-dependent changes were evidenced in the diabetic group, as only males showed increased glycemia as well as increased concentrations of nitrated proteins, matrix metalloproteinase-9 and peroxisome proliferator activated receptor α (PPARα) in the heart. Differently, the heart of male and female offspring of diabetic rats showed increased levels of connective tissue growth factor (CTGF). Maternal treatments with idebenone, a mitochondrial antioxidant, led to reductions in all the pro-oxidant and pro-inflammatory markers evaluated and in PPARα protein expression in the heart of the offspring of diabetic rats. The results of the present study highlight the gender dependence and the role of oxidative stress in the diabetes-induced intrauterine programming of heart alterations.