title: Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats.
abstract: BACKGROUND
  Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals.
  
  
  OBJECTIVE
  We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats.
  
  
  METHODS
  Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process.
  
  
  RESULTS
  LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2).
  
  
  CONCLUSIONS
  Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.
authors.affiliation: School of Applied Sciences, University of Campinas, Limeira, Brazil.|Department of Physiology and Biophysics, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Hosana G
authors.initials: HG
authors.lastname: Rodrigues
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Marco A R
authors.initials: MA
authors.lastname: Vinolo
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Fabio T
authors.initials: FT
authors.lastname: Sato
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Magdalon
authors.affiliation: School of Applied Sciences, University of Campinas, Limeira, Brazil.
authors.forename: Carolina M C
authors.initials: CM
authors.lastname: Kuhl
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Yamagata
authors.affiliation: Cell and Developmental Biology Department, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Ana Flávia M
authors.initials: AF
authors.lastname: Pessoa
authors.affiliation: Cell and Developmental Biology Department, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Malheiros
authors.affiliation: Cell and Developmental Biology Department, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Marinilce F
authors.initials: MF
authors.lastname: Dos Santos
authors.affiliation: Department of Clinical and Toxicology Analyses, School of Pharmaceutical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Lima
authors.affiliation: Department of Clinical and Toxicology Analyses, School of Pharmaceutical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Farsky
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Camara
authors.affiliation: Food Sciences and Nutrition, School of Biochemistry and Biological Sciences, National University of Litoral, Santa Fé, Argentina.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Williner
authors.affiliation: Food Sciences and Nutrition, School of Biochemistry and Biological Sciences, National University of Litoral, Santa Fé, Argentina.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Bernal
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.|NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
mesh_terms: D000284:Administration, Oral; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D005786:Gene Expression Regulation / Q000187:drug effects; D019787:Linoleic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D042702:Angiopoietin-2; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013311:Streptozocin; D019787:Linoleic Acid