Potencial cardioprotetor da restrição calórica: influência sobre o estresse oxidativo e a sinalização para inflamação

Abstract

Estrogen is an steroid hormone that promotes cardioprotection for combaingt oxidative stress and inflammation. Their low levels, such as after women menopause, increase the propensity to cardiovascular disease. Such diseases are the leading causes of death in Western countries, predominantly affects women after menopause. In this context, it has been increasingly encouraged the discovery of prophylactic therapies which can prevent/delay the pathogenesis of cardiovascular diseases. Caloric restriction (CR) has shown promising role in this regard, althought the mechanisms are not well known. Therefore, it becomes essential to deepen in the investigation of the mechanisms involved in order to suggest new therapeutic approaches. The aim of the study was to determine whether the CR is able to modulate the influence exerted by estrogen on some risk factors associated with cardiovascular diseases. For this, it was used 20 rats Wistar shared in 4 experimental groups (FC-diet ad libitum; FRC-caloric restriction 30%; FOC-diet ad libitum and ovariectomy; FORC-caloric restriction 30% and ovariectomy). After diet acclimatization, they were subjected to CR 30% until the day of sacrifice. Spent 5 weeks of CR 30%, the rats were ovariectomy bilateral castrated or subjected to the same simulation in deep anesthesia. After that, they remained in 30% CR for another 4 weeks, totalizing 9 weeks in 30% CR. After sacrifice by decapitation, blood collection was performed for measurements of serum lipids and paraoxanase 1, and cardiac tissue to oxidative stress measurements and quantification of protein expression TLR4 and NF-kB by western blot. As a result, it was observed that the rats submitted to CR had a gain weight rate less than those fed ad libtum, even with lack of estrogen. In serum parameters, CR decreased the TG of FRC rats compared to FC and estrogenic shortage increased CT levels in FOC rats compared to FC and also raised HDL both in FOC and in FORC. The activity of PON1 was similar in all groups. Already the PON1 / HDL ratio was significantly reduced in the FOC and FORC groups in relation to their control groups. Regarding the oxidative stress parameters evaluated in the heart, the activity of the antioxidant enzyme SOD was lower in rats with less estrogen, the CR was able to decrease lipid peroxidation and total antioxidant capacity was increased in FOC and FRC groups against the FC group. The FORC group had a lower total antioxidant capacity compared to its control (FRC and FOC). As the protein expression of TLR4, we observed a decrease in FOC and FRC groups against the FC group, which did not differ from FORC group. The expression of NF-kB was significantly lower in FORC group compared to the FRC group. We conclude the CR 30%, when promoting the reduction of the expression of key proteins to intracellular signaling of inflammation and cell death, has potential benefit in preventing heart damage caused by estrogen shortage.