Efeito de terpenos no envelhecimento cardiovascular: o papel da senescência e do estresse oxidativo

Abstract

The population over 60 is growing substantially, reaching 22% in 2050. Cardiovascular diseases (CVDs), the leading cause of morbidity and mortality around the world, have an increased prevalence with age. Therefore, strategies are urgently needed to combat and/or prevent them. In this context, this work aimed to evaluate the anti-senescent effect of 20 terpenes and characterize the effect of the most promising in vitro and in vivo. For this, rat aortic endothelial cells (RAEC) and Wistar rats were used. D-(+)Galactose (Dgal) was used as an aging model. Initially, a triple screening was performed for anti-senescent cell viability and antioxidant action with 20 terpenes. Terpinolene (TPO) was effective in the three trials, with concentrations of 10-7 and 106 mo.L-1 having a triple beneficial effect. The Annexin V/7-AAD assay confirmed the ability of TPO to improve cell viability. For in vivo tests, doses of 5 and 25 mg/kg were used for 56 days. In parallel, the animal received saline or Dgal intraperitoneally to induce the accelerated aging model. During treatment, there were no changes in the body weight of the groups. The day before euthanasia, systolic blood pressure and heart rate were evaluated without significant changes. Capillary glycemia was unchanged between the CTL group (108.00 ± 1.64; n=8) and Dgal (111.87 ± 2.30; n=8); however, the TPO25 group had a reduction in glycemic levels (103.12 ± 2.57; n=8 ). After the anaesthetic, electrocardiographic recordings were carried out, with subsequent blood collection for biochemical and haematological tests and removing the aorta artery and the heart, liver, and kidney organs. The biochemical parameters were divided into lipid, protein, renal, and hepatic. Furthermore, total protein levels were elevated in the Dgal group compared to CTL, and TPO5 and TPO25 restored these levels. The haematological profile was unchanged between the groups. However, for coagulation tests, the increased TP in the Dgal group was restored to baseline levels by TPO25. The TPPA did not detect changes between the groups, as well as platelet reactivity. Furthermore, tests were performed for vascular reactivity in aortic rings, which showed no significant changes between the groups in Emax for contraction against FEN nor relaxation induced by NPS. On the other hand, AChinduced relaxation was compromised in the Dgal group (Emax: 85.20 ± 2.18; n=8) when compared to the CTL group (Emax: 100.5 ± 2.40; n=6) and restored by TPO25 (Emax: 98.60 ± 2.91; n=7). This finding was accompanied by vascular oxidative stress, evidenced by the DHE probe in the CTL (100.00 ± 4.05; n=6), DGAL (157.59 ± 6.01; n=6) groups, restored by TPO25 (105.28 ± 6.96; n=6). Finally, we analyzed the electrocardiographic aspects, such as P wave duration with an upward trend in the Dgal group compared to the CTL, restored by TPO25. Furthermore, the cardiac hypertrophy index in Dgal (0.360 ± 0.012, n=8) increased in relation to CTL (0.312 ± 0.011, n=7) and was restored by TPO25 (0.301 ± 0.006, n=10). Therefore, the TPO selected by Screening was able to exert beneficial effects on cardiovascular aging, being a promising candidate in the search for healthy aging.