Antioxidant flavonoids as a therapy in the prevention and treatment of endothelial dysfunction in obese rats

Abstract

Obesity is a worldwide public health problem and its treatment includes limited dietary intake of saturated fats and physical activity. Obesity causes several organic dysfunctions such as vascular dysfunctions because of the reduced bioavailability of vasodilatory substances such as nitric oxide (NO). There are evidences that the reduced vasodilatory substances are related to increased reactive oxygen species (ROS), which leads to an oxidative stress. On the other hand, in obesity there is an increase in the expression/activity of Rho-kinase pathway proteins/enzymes, favoring the contractile state of the smooth muscle, and decreasing NO induced relaxation. Additionally, the intake of antioxidant flavonoids has been largely proposed as a therapy for cardiovascular disorders. However, the main limitation of bioavailability of glycosylated flavonoids regards to its intestinal absorption. Hence, one way to increase the bioavailability of glycosylated antioxidants is to promote its hydrolises using enzymes which are capable to release the glycosidic fraction and make more active compounds. Therefore, the aim of this work is to evaluate the effects of hesperidin, an antioxidant flavonoid with activity on the lipidic metabolism, before and after its enzymatic hydrolysis, in association (or not) with physical exercise, on the vascular function of obese rats. Specifically, it will be evaluated whether these treatments improve vascular reactivity and regulate the oxidative state of the vascular tissue and modulate calcium sensitization (Rho-kinase pathway). Obesity will be induced by a hyperlipidic diet plus fructose given to 4 weeks-old male Wistar rats, lasting 12 weeks. Physical training and/or antioxidant treatment will start along with the 5th week of diet and will last 8 weeks further. It will be evaluated the tolerance to physical exercise, mean blood pressure, lipid profile and aorta and mesenteric artery will be removed for functional and structural evaluation and further protein quantification. (AU)