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Evaluation of the protective action of melatonin on the oxidative stress induced by obesity in the aortic perivascular adipose tissue

Grant number: 18/23959-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2019
Effective date (End): March 31, 2020
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Carlos Renato Tirapelli
Grantee:Sabrina Paixão Ficher
Home Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Perivascular adipose tissue (PVAT) is a type of adipose tissue that surrounds large arteries and veins. In addition to provide mechanical support to the blood vessels, PVAT also function as a paracrine and endocrine organ. PVAT secretes several bioactive substances that exert anti-contractile effect thus modulating the vascular response to different vasoactive agents. In obesity, there is an increase in the amount and structural modification of PVAT along the vasculature. These changes include increased reactive oxygen species (ROS) via NAD(P)H oxidase and reduced antioxidant capacity. Together these responses lead to increased oxidative stress, reduced anti-contractile action of PVAT and vascular dysfunction. Melatonin (5-methoxy-N-acetyltryptamine) is a hormone produced centrally by the endocrine cells of the pineal gland. This hormone has been used to protect against oxidative damage and modulation of the anti-inflammatory response in the cardiovascular system. Melatonin is also able to prevent oxidative damage in the aorta of diabetic and septic rats. In obese mice aorta, melatonin restores the levels of superoxide dismutase (SOD) 2 and catalase. In addition, in mesenteric arteries, melatonin prevents the loss of the anti-contractile function of PVAT in a model of senescence. Melatonin has been used in several animal models of obesity as a pharmacological tool for weight reduction and obesity-induced changes. However, there are no studies in the literature that describe the effect of melatonin on the maintenance of oxidative stress and its role in the loss of the anti-contractile function of PVAT during obesity. The hypothesis of this work is that the increase of oxidative stress observed during obesity is associated with the loss of the anti-contractile function of PVAT and that the treatment with melatonin acts directly in the reduction of oxidative stress as a scavenger of free radicals and, indirectly, stimulating the activity and expression of antioxidant enzymes. Thus, the present project was designed with the objective of investigating whether melatonin could reverse the increase of oxidative stress in PVAT induced by obesity.