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

• Grant number: 12/04325-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2013
• End date: November 30, 2015
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Lusânia Maria Greggi Antunes
• Grantee: Carla da Silva Machado
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANTUNES, L. G.; MACHADO, C. S.; AISSA, A. F.; RIBEIRO, D. L.. Evaluation of DNA damage and modulation of gene expression in the heart of rats that received vitamin D3 supplemented or deficient diets. Toxicology Letters, v. 295, p. 1-pg., 2018-10-10. (12/04325-9)

MACHADO, CARLA DA SILVA; VENANCIO, VINICIUS PAULA; AISSA, ALEXANDRE FERRO; HERNANDES, LIVIA CRISTINA; DE MELLO, MICHELA BIANCHI; CAVALCANTI DEL LAMA, JOSE EDUARDO; GREGGI ANTUNES, LUSANIA MARIA. Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 798, p. 19-26, MAR 2016. (12/04325-9)

MACHADO, CARLA DA SILVA; AISSA, ALEXANDRE FERRO; RIBEIRO, DIEGO LUIS; GREGGI ANTUNES, LUSANIA MARIA. Vitamin D supplementation alters the expression of genes associated with hypertension and did not induce DNA damage in rats. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 82, n. 4, p. 299-313, FEB 16 2019. (12/04325-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACHADO, Carla da Silva. Evaluation of genomic instability, oxidative stress and modulation of gene expression by vitamin D in a model of spontaneously hypertensive rats. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.