Study of Palmitoleic Acid in Mechanisms Involved in the Wound Healing Process

• Grant number: 11/15360-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Elaine Hatanaka Dermargos
• Grantee: Eleine Weimann
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

Wound healing defines a series of events aimed at restoring the injured tissue. This process is divided into three phases: (i) inflammation, (ii) formation of granulation tissue with deposition of extracellular matrix and (iii) remodeling. The healing process has a fine regulation of specific signals that are triggered by diferents cell types and that can be modulated by fatty acids. Several studies have been demonstrating the beneficial effect of topical application of fatty acids in the treatment of wounds, as follows: (a) fatty acids are substances that have low cost and it are widely used as healing agents by the popular culture of different countries, (b) oils acts as a protective barrier against microorganisms, prevents dehydration, keeps the body temperature and decrease injuries while changing the dressings, (c) studies involving the role of fatty acids on immune system cells show the important immunomodulatory functions (d) fatty acid nutritional deficiency slows the healing process. Although the effects of fatty acids in modulating the inflammatory response is largely studied, the role of fatty acids in the tissue repair are poorly understood. Palmitoleic acid is found in the skin, especially in young and as we age, the amount palmitoleic acid skin decreases. Macadamia oil, rich in palmitoleic and oleic acid is used to treat wounds and as a cosmetic, but little is known about the mechanisms of action of this substance. Thus, this study aims to determine the effects of palmitoleic acid in cells at different stages of the healing process, through in vitro and in vivo, studies: (i) In vivo studies: injured rats, will be treated topically with palmitoleic acid and after that we will perfomed: (a) Macroscopic analysis of the healing process, (b) analysis of cellularity and (c) detection of TNF-±, IL-1², CINC-2± / ², MIP-1 a, a-VEGF and collagen produced locally at different times. (II) In vitro studies: We will study the influence of wound of the following functions of neutrophils and macrophages (a) chemotaxis, (b) respiratory burst (c) microbicidal activity, (d) release of TNF-±, IL- 1², CINC-2± / ², MIP-1 and VEGF-a a. In fibroblasts will be evaluated the effect of palmitoleic acid on the production of reactive oxygen species, proliferation and release of cytokines and growth factors (FGFs and VEGF-a) and collagen. Data from in vivo experiments will be correlated with data obtained in vitro experiments. Our future outlook is that, if occurs any beneficial effect, these are highlighted as well as the specific mechanism involved. We believe that if the palmitoleic acid has a possitive effect on the tissue repair process the mechanisms of action need to be studied for the further possibility of developing formulations (biomembranes, gels, ointments) for application in humans.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

WEIMANN, ELAINE; BARROS SILVA, MAYSA BRAGA; MURATA, GILSON MASAHIRO; BORTOLON, JOSE RICARDO; DERMARGOS, ALEXANDRE; CURI, RUI; HATANAKA, ELAINE. Topical anti-inflammatory activity of palmitoleic acid improves wound healing. PLoS One, v. 13, n. 10, OCT 11 2018. (11/15360-7, 14/03947-1)

WEIMANN, E.; BELMIRO, B.; SILVA, M. B. B.; MURATA, G. M.; BORTOLON, J. R.; DERMARGOS, A.; HATANAKA, E.. Anti-inflammatory effect of palmitoleic acid on effector mechanisms of neutrophils. FEBS OPEN BIO, v. 8, p. 1-pg., 2018-07-01. (11/15360-7, 14/03947-1)