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Effects of vitamin B12 supplementation in young rats: investigations of genome instability, gene expression profile, and DNA methylation of the genes GR, ppara and mtp involved in cardiovascular disease

Grant number: 10/14862-6
Support type:Regular Research Grants
Duration: December 01, 2010 - November 30, 2012
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Maria de Lourdes Pires Bianchi
Grantee:Maria de Lourdes Pires Bianchi
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Alexandre Ferro Aissa ; Lusânia Maria Greggi Antunes ; Tarsila Daysy Ursula Hermogenes Gomes

Abstract

Effects of vitamin B12 supplementation in young rats: investigations of genome instability, gene expression profile, and DNA methylation of the genes GR, PPARA and MTP involved in cardiovascular diseaseIn the last 12 years our group has been investigating the benefits of dietary antioxidants and its interactions with the antitumor drugs cisplatin and doxorubicin. One of the main focus areas is the possible activities antimutagenic and citoprotector of carotenoids, phenolics and vitamins. Recently, the line of research in Nutrigenomic was established in our laboratory, with support of the FAPESP (Processes 06/55035-0 and 06/61237-4). Nutrigenomics investigates the effects of foods and food components to define how diet-gene interactions influence metabolic and homeostatic pathways that influence a phenotype. The interaction between genotype and diet in the modulation of the risk of development of degenerative diseases emerges as a promising area of the research as for the effect of micronutrients on the DNA. Research in nutrigenomic is emerging as important field because it is each more evident that the risk for degenerative diseases increases with the damage to the DNA that, in turn, is dependent of the level of micronutrients required for the repair and response of the genome. Dietary reference values are intended to provide a guide for the appropriate intake of nutrients for prevention of diseases caused by deficiency or supplementation. Determining these extremes is very important. During the reproductive process, the genome of mammals undergoes a profound reprogramming of methylation patterns in germ cells and in the early stages of pre-implantation embryo. It has been suggested that an inadequate diet during the embryonic development can have delayed consequences in the adult life of the organism. Therefore, disruption of the methylation pathway may cause epigenetic defects during the embryonic period and favor the emergence of diseases throughout the life of the individual. Therefore, this study aims is to investigate the DNA methylation and expression of GR, PPARA and MTP, genes involved in the cardiovascular disease, in the liver of the offspring of rats submitted to a diet supplemented with vitamin B12, also evaluating the influence of this supplementation in the genome instability by the comet assay in the liver and the micronucleus test in peripheral blood.Keywords: comet, nutrigenomics, vitamin, micronucleus, mutagenesis (AU)