Abstract
The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.
Highlights
The effect of high adherence to a Mediterranean-type diet has been widely demonstrated to reduce the incidence of any type of cardiovascular disease and mortality from any cause [1,2]
The results obtained in the present study showed that the experimental model of diabetes used in this study presented an evident oxidative and nitrosative stress, as well as an increase in the biomarkers involved in cardiovascular disease in humans, which justified its use to study the association of HT and DHPG in a disease that is a risk factor for cardiovascular disease
In this study we demonstrated that DHPG showed these effects in ex vivo conditions in a model of diabetes mellitus, as well as the synergistic effect of both polyphenols in the inhibition of these mediators of cardiovascular damage
Summary
The effect of high adherence to a Mediterranean-type diet (high content in fruits, vegetables, legumes, fish, and extra-virgin olive oil) has been widely demonstrated to reduce the incidence of any type of cardiovascular disease and mortality from any cause [1,2]. The main source of fat in this diet is extra-virgin olive oil (EVOO). There is much evidence that shows that a large part of the beneficial effects of the Mediterranean diet are 4.0/). Antioxidants 2021, 10, 1983 due to the intake of EVOO [3]. It is even established that the necessary amount of EVOO to demonstrate these effects, especially at the cardiovascular level, is 25–50 g/day [4,5]. Many studies have been published, both experimental studies and studies of humans, on the influence of EVOO on certain biomarkers that are altered in cardiovascular diseases: oxidation of low-density lipoproteins (oxLDL), platelet and endothelial dysfunction, oxidative stress, inflammatory mediators, etc. [4,6,7]
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