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Vitamin C in gene expression of oxidative stress markers on cultivated fibroblasts from patients with burn injury

Grant number: 15/02161-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2015
Effective date (End): September 30, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alfredo Gragnani Filho
Grantee:Marcelo Moraes Trincado
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

INTRODUCTION: Burn injury is a major public health problem in the world. Occur, each year, more than 300,000 deaths caused by accidents with fire, without considering the scald burns, electrical burns, chemical burns and other forms that do not have their statistics available on global levels. During a burn at the molecular perspective, both the activation of the complement system and the stimulation of intravascular neutrophils result in the production of reactive oxygen species (ROS). Increased activity of histamine, reinforced by the catalytic properties of xanthine oxidase causes a progressive local increases in vascular permeability. Toxic byproducts of xanthine oxidase, including hydrogen peroxide (H2O2) and hydroxyl radical (OH) appear to damage directly dermal structures. The initial response to burn injury is often associated with secondary damage to other tissues distant from the thermally injured site. This response appears to be mediated by ROS and activated neutrophils. The production of ROS and RNS in a burn may have implications for mechanical responses, patolológica and cell signaling in affected organs, causing damage to cells of the immune system attacking and damaging cellular components like proteins, lipids and DNA. The defense mechanisms against oxidative stress induced by free radicals involve: (i) prevention mechanisms, (ii) repairing mechanisms, (iii) physical defenses and (iv) antioxidant defenses. Enzymatic antioxidant defenses include superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT). Non-enzymatic antioxidants are represented by ascorbic acid (vitamin C), alpha tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids and other antioxidants (VALKO et al., 2007). Glutathione peroxidase is essential for the conversion of glutathione to oxidized glutathione during H2O2 is converted into water. Vitamin C (ascorbic acid) is a water-soluble micronutrient necessary for many biological functions. It acts as a cofactor in enzymatic reactions such as the synthesis of collagen and is an important antioxidant in human plasma, removing free radicals and protecting the organism against lipid peroxidation. Reduced plasma levels of vitamin C were found in burned patients who developed multiple organ failure, compared with higher levels in patients who did not develop multiple organ failure.METHODS: This study has an experimental research design, in vitro, interventional analytical, controlled, conducted in a single center. Study groups will be divided into: fibroblast culture with ascorbic acid from burnt patients; fibroblast culture without ascorbic acid from burnt pacients. To obtain skin samples necessary for the development of the research, a standard surgical procedure used for the treatment of burned-discipline of Burn Care Unit of Plastic Surgery UNIFESP-HU / HSP and the skin sample will be conduced to the laboratory insted of be discarded.OBJECTIVE: Evaluate the action of vitamin C in the expression of 84 genes related to oxidative stress in cultured dermal fibroblasts from the skin of burnt patients.COMMENTS AND CONSIDERATIONS SEARCH: It is expected that the dermal cells treated with ascorbic acid, from burnt patients, when compared to the control group, alter the expression patterns in some of 84 genes related to oxidative stress that will be analyzed.