title: Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model.
abstract: Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans.
authors.affiliation: School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Carla da Silva
authors.initials: Cda S
authors.lastname: Machado
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Vinicius Paula
authors.initials: VP
authors.lastname: Venancio
authors.affiliation: School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil; School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Alexandre Ferro
authors.initials: AF
authors.lastname: Aissa
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Lívia Cristina
authors.initials: LC
authors.lastname: Hernandes
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Michela Bianchi
authors.initials: MB
authors.lastname: de Mello
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: José Eduardo Cavalcanti
authors.initials: JE
authors.lastname: Del Lama
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Cleni Mara
authors.initials: CM
authors.lastname: Marzocchi-Machado
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Maria Lourdes Pires
authors.initials: ML
authors.lastname: Bianchi
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil. Electronic address: lusania@fcfrp.usp.br.
authors.forename: Lusânia Maria Greggi
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D000818:Animals; D002762:Cholecalciferol / Q000172:deficiency* / Q000502:physiology / Q000627:therapeutic use; D004249:DNA Damage; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species; D016897:Respiratory Burst
chemical_list: D017382:Reactive Oxygen Species; D002762:Cholecalciferol
keywords: Cholecalciferol; Comet assay; Hypertension; Micronucleus; Oxidative stress; SHR