"Evaluation of genomic instability, oxidative stress and modulation of gene expression by vitamin D in a model of spontaneously hypertensive rats"

Abstract

In recent years, our group has focused on the line of research in Nutrigenomics, which .the aim of linking technologies "omics" to cytogenetic and biochemical studies to better understand the mechanisms of action of dietary components in health promotion. Unbalanced diets, from deficiencies to excess consumption of micronutrients, macronutrients or dietary supplements may alter metabolism and enhance the development of chronic diseases like cancer, diabetes and cardiovascular diseases. One of the essential micronutrients, vitamin D has recently been associated with the development of endocrine and cardiovascular regulation and expression of genes involved in the production of rennin, proliferation in the liver and heart muscle cells and vascular diseases. Vitamin D is synthesized in the skin following UV exposure and obtained in the diet after consumption of fatty fish like salmon, sardines and mackerel, and foods fortified with vitamin D such as milk and dairy products. The deficiency of this vitamin is present in 30-50% of population, and epidemiological studies have revealed an association between diets deficient in vitamin D and a rise in blood pressure. Vitamin D influences the activation of the renin-angiotensin-aldosterone system, an endocrine axis involved in maintaining hemodynamic stability, and the main regulator of blood pressure. Considering that hypertension is a risk factor for the development of diseases that affect the systems heart, renal and peripheral vascular, that vitamin D plays an important role in cardiovascular physiology and modulation of the expression of genes related to hypertension by vitamin D is unknown, the purpose of this project is to evaluate the effect of diets deficient or supplemented with vitamin D on modulation of the expression of genes related to hypertension by the technique of RT2 Profiler PCR Array in the heart and kidneys of adult spontaneously hypertensive rats(SHR) and normotensive Wistar Kyoto (WKY). Additionally, to evaluate changes in blood pressure and histology of kidneys, genomic instability in heart, kidney, liver, bone marrow and peripheral blood using the comet assay and micronucleus test, biochemical markers of oxidative stress by assays of oxidative damage in isolated blood neutrophils, determination of thiobarbituric acid reactive substances and dosage of glutathione, and the measurement of metabolite 25-hydroxy-vitamin D3 in the plasma.