Journal Article

Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats

dos Santos, Marinilce F., Lima, Camila, Pessoa, Ana Flávia M., Malheiros, Gabriella, Curi, Rui, Vinolo, Marco A. R., Rodrigues, Hosana G., Camara, Niels O. S., Magdalon, Juliana, Sato, Fabio T., Kuhl, Carolina M. C., Williner, Maria R., Bernal, Claudio A., Farsky, Sandra H., Yamagata, Ana S., Calder, Philip C.

2016

Overview

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. We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. 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. 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). Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Administration, Oral / Angiogenesis / Angiopoietin / Angiopoietin-2 - metabolism / Animal tissues / Animals / Biochemistry / Biology and Life Sciences / Biophysics / Cancer / Cell adhesion & migration / Cell migration / Cell Movement - drug effects / Chemotaxis / Cytokines / Cytokines - metabolism / Developmental biology / Diabetes / Diabetes mellitus / Diabetes Mellitus, Experimental - complications / Eicosanoids / Fatty acid composition / Fatty acids / Gene Expression Regulation - drug effects / Growth factors / Inflammation / Leukocyte migration / Leukocytes / Leukotriene B4 / Linoleic acid / Linoleic Acid - administration & dosage / Linoleic Acid - pharmacology / Macrophage inflammatory protein / Macrophage inflammatory protein 1 / Macrophages / Medicine and Health Sciences / Monocyte chemoattractant protein 1 / Neovascularization, Physiologic - drug effects / Neutrophils / Nutrition / Oral administration / Pharmaceutical sciences / Physiology / Rats / Rodents / Skin / Streptozocin / Toxicology / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Unsaturated fatty acids / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - metabolism / Wound care / Wound healing / Wound Healing - drug effects