Name: BRUNO MAIA COSTA
Publication date: 08/02/2021
Advisor:
Name |
Role |
|---|---|
| GLAUCIA RODRIGUES DE ABREU | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| CÍNTIA HELENA SANTUZZI | External Examiner * |
| GLAUCIA RODRIGUES DE ABREU | Advisor * |
| SONIA ALVES GOUVEA | Internal Examiner * |
Summary: Oxidative stress, resulting from cardiovascular disease and estrogen deficiency, is a favorable condition for the development of ventricular diastolic dysfunction as well as progression and severity of cardiac insufficiency. In this sense, studies seek new therapeutic options that can reduce oxidative stress through natural alternative therapy, in which ellagic acid (EA) has been shown as an option for presenting antioxidant properties. The aim of this study was to analyze whether treatment with EA can reduce the production of reactive oxygen species (ROS) and preventing diastolic dysfunction (DD), as well as investigating CaMKII's involvement in this pathophysiology. Wistar rats were ovariectomized and subdivided into 4 groups: SHAM diastolic dysfunction (Sham); Sham + EA; DD; DD + EA. Treatment with EA was carried out for 4 weeks, starting on the first day after induction of DD. At the end of treatment, cardiac hemodynamics was performed to analyze the systolic (LVSP) and final diastolic pressure of the left ventricle (LVEDP) and the maximum LV contraction and relaxation derivatives (dP/dt+ and dP/dt-, respectively). Cardiac oxidative stress "in situ" was evaluated by dihydroethidium fluorescence, CaMKII protein expression and pro and antioxidant enzymes by Western blotting, as well as antioxidant enzymatic activity by spectrophotometry. The animals with DD showed an increase in LVEDP and a reduction in the derivatives dP/dt + and dP/dt-, however, the treatment with EA attenuated the LVEDP and, in addition, it reduced the LVSP in the DD+EA group. The high production of EROS in the DD group was accompanied by an increase in gp91phox expression and a reduction in superoxide dismutase (SOD-2), which was reversed in the DD+EA group together with the increase in catalase expression. An increase in SOD activity was observed in the DD+EA group, on the other hand, the same did not occur with catalase. In addition, treatment with EA reduced CaMKII activation, analyzed by the low expression of p-CaMKII in the treated DD group, compared to the untreated one. Therefore, it is concluded that treatment with EA is able to attenuate diastolic dysfunction in an experimental model of menopause, via reduction of oxidative stress associated with decreased p-CaMKII, which makes EA a promising natural therapeutic option for better prognosis of cardiac dysfunction in women affected during menopause.
