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Effects of eicosapentaenoic omega-3 fatty acid (EPA) supplementation on wound healing in diabetic mice: focus on the NLRP3 pathway

Grant number: 18/00529-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2018
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Physiology - General Physiology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Hosana Gomes Rodrigues
Grantee:Beatriz Burger
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Associated research grant:13/06810-4 - Mechanisms of action of omega-3 and omega-6 in the tissue repair process: neuro-immune focus, AP.JP
Associated scholarship(s):19/00481-5 - Effects of omega-3 fatty acids in bioactive metabolome in macrophages of human blood and diabetic mice scar tissue, BE.EP.MS


The skin is the first immunological barrier against physical, chemical or biological agents from the external environment and thus, must be repaired quickly when damaged. However, the delay in wound healing affects millions of people worldwide increasing susceptibility to infections, amputations and death, especially in diabetic individuals. Studies conducted by our group have demonstrated that the oral administration of omega-6 (É-6) and omega-9 (É-9) fatty acids accelerates the inflammatory response in wound healing in rats. On the other hand, É-3 fatty acids impair healing in normal mice by inhibiting the inflammatory response. However, the effects of these fatty acids on wound healing in diabetics are unknown. Preliminary data show that É-3 fatty acids inhibit the production of interleukin-1² (IL-1²) in the inflammatory phase of wound healing in diabetic animals. One of the pathways that regulate the production / activation of IL-1² is the inflammassome, mainly NLRP-3. Thus, in the present study we will investigate the effects of oral administration with É-3-rich oil during the healing process in diabetic animals, focusing on the NLRP3 inflammatory pathway. For this purpose, male C57Black / 6 mice, with streptozotocin-induced diabetes, will be divided into two groups: (D) diabetics; (EPA-D) diabetic animals that will receive EPA. The animals will receive EPA rich oil for four weeks and then the wounds will be done on the backs of the animals. The analyzes of scar tissue will be performed at times 0h, 1, 3, 7, 10, 14 and 21 days. The methods to be used will be macroscopic wound closure analysis, mass spectrometry for the quantification of lipid inflammatory mediators, ELISA (Immunoenzymatic Assay) to quantify inflammatory mediators, flow cytometry for cellular immunophenotyping, immunoblot and PCRrt for the evaluation of the proteins of the inflammoma complex NLRP3. In addition, animal knockouts for NLRP3 will be used to evaluate the importance of NLRP3 for the tissue repair process in diabetic mice supplemented with EPA. The data will be analyzed Student's t test or ANOV A One-way. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BURGER, Beatriz. Effects of eicosapentaenoic (EPA) omega-3 fatty acid supplementation on wound healing in diabetic mice. 2019. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.

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