Effects of eicosapentaenoic (EPA) omega-3 fatty acid supplementation on wound healing in diabetic mice

Author(s)

Beatriz Bürger

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2019-11-11

Examining board members

Hosana Gomes Rodrigues; Dennys Esper Cintra; Daniela Carlos Sartori

• Advisor: Hosana Gomes Rodrigues

Abstract

The skin is the first immune barrier against physical, chemical or biological agents from the external environment and thus must be repaired quickly when damaged. Delayed wound healing results in longer hospital stays, high costs to health services and poor quality of life. Such delay may be related to diseases such as diabetes mellitus (DM). Although several therapeutic approaches have been developed for the wound healing of diabetic patients in recent years, diabetic ulcer remains a major clinical challenge. Omega-3 (?-3) eicosapentaenoic fatty acid (EPA, 20:5) impairs collagen reorganization in healthy mouse wounds by increasing IL-10 in scar tissue. However, the effects of these fatty acids on wound healing in diabetic patients are unknown, so the aim of present study is investigating the effects of oral administration with EPA rich oil on the wound healing in diabetic mice. C57Black/6 male mice were divided into three groups: (C) Control that received water as placebo; (D) diabetics with streptozotocin-induced diabetes and were supplemented with water; (ED) diabetic animals that received oral supplementation of EPA-rich oil. We evaluated macroscopic wound closure, histological characteristics of scar tissue, wound tensile strength; cell immunophenotyping by flow cytometry, cytokine quantification by ELISA, collagen gene expression by quantitative PCR. In the inflammatory phase (1 and 3 days), diabetic animals reduced the proinflammatory cytokines (TNF-? and IL-6) which may be related to the reduction of granulation tissue in these animals. In the proliferative phase (7 and 10 days) there was an increase of cytokines (IL-1?, IL-6) and chemokine CXCL1, with consequent increase of inflammatory infiltrate and edema in granulation tissue. EPA-rich oil supplementation in diabetic mice increased the concentration of anti-inflammatory cytokine IL-10 in the inflammatory phase, which may be related to reduced neutrophil migration to scar tissue. In the proliferative phase, EPA-rich oil also had anti-inflammatory effects such as increased IL-10 and neutrophil/macrophage ratio indicating a reduction in apoptotic neutrophil phagocytosis. Reduction of 1A1 collagen gene expression was also observed, and consequently increased fragility of scar tissue. Cellular and molecular changes during wound healing in diabetic mice supplemented with EPA-rich oil produced a less resistant tissue and easier to be broken again. Keywords: Tissue repair, diabetes, omega-3, collagen (AU)

• FAPESP's process: 18/00529-5 - Effects of eicosapentaenoic omega-3 fatty acid (EPA) supplementation on wound healing in diabetic mice: focus on the NLRP3 pathway
• Grantee: Beatriz Burger
• Support Opportunities: Scholarships in Brazil - Master