Effects of Paroxetine on Cutaneous Wound Healing in Healthy and Diabetic Rats Esra Pancar Yuksel, MD; Fatih Ilkaya, MD; Levent Yildiz, MD; Fatma Aydin, MD; Nilgun Senturk, MD; Hilal Denizli, MD; Tayyar Canturk, MD; and Ahmet Yasar Turanli, MD ABSTRACT OBJECTIVE: The aim of this study was to evaluate the histologic effects of acute paroxetine administration on wound healing in healthy and streptozotocin-induced diabetic rats. DESIGN: This study has a randomized controlled experimental design. SETTING: Healthy (n = 32) and diabetic (n = 32) rats were further divided into 2 groups of saline or paroxetine administration. PARTICIPANTS: Sixty-four male Sprague-Dawley rats were used in this study. INTERVENTIONS: Paroxetine was injected intraperitoneally every day. Full-thickness excision wounds were created with a 4-mm dermal punch on the back of all rats. The healing wound area was removed with a 6-mm dermal punch at postwounding days 1, 3, 7, and 14. MAIN OUTCOME MEASURES: Polymorphonuclear leukocyte, mononuclear inflammatory cell, fibroblast, and blood vessel counts and epithelialization were evaluated under light microscope. MAIN RESULTS: There was no statistically significant difference observed in the polymorphonuclear leukocyte, mononuclear inflammatory cell, and blood vessel counts in the healthy and diabetic rats with and without paroxetine administration. The number of fibroblasts was significantly higher at postwounding day 14 of the paroxetine-administered healthy rats compared with the saline-administered healthy rats ( P = .04). However, the number of fibroblasts did not show any difference by paroxetine administration in the diabetic rats. There was no statistically significant difference in epithelialization regarding all the postwounding days, but complete epithelialization was observed in all rats on postwounding day 14 in the healthy and paroxetine-administered group. CONCLUSION: Short-term paroxetine administration may enhance cutaneous wound healing by increasing the number of fibroblasts and causing better epithelialization over time in healthy rats but not in diabetic rats. KEYWORDS: paroxetine, cutaneous wounds, epithelialization, fibroblasts ADV SKIN WOUND CARE 2014;27:216Y21 INTRODUCTION Wound healing represents the complex process involving the in- teraction of several types of cells, cytokines, and mediators. It has 3 phases: inflammation, proliferation, and remodeling. During these phases, polymorphonuclear leukocytes (PMNs) appear within 24 hours, replaced by macrophages by day 3, followed by neovas- cularization and proliferation of fibroblasts seen on the second week. 1,2 The PMN count increases after injury, and these PMNs function in phagocytosis of invading microbes, necrotic tissue, and the release of cytochemoattractants. Neutrophils exist within the wound longer in case of wound contamination and may result in delayed healing. 1,3 After entering the wound site, monocytes dif- ferentiate into tissue macrophages that proliferate within the wound, clearing the wound of contaminating microbes as well as nonviable tissue. These monocytes are also responsible for the formation of oxygen-free radicals, inflammatory cytokines, and tissue growth factors to induce the proliferative phase of the repair process and a new connective tissue matrix. The proliferative phase includes re-epithelialization, angiogenesis, and fibroplasia. Fibroblast pro- liferation occurs as an early response to injury in the fibroplasia process, and new vessel formation from the preexisting vessels is part of the angiogenesis. 1,3,4 It is known that there are many local and systemic factors that can disturb this repair process. Of these factors, diabetes mellitus is one of the well-known systemic dis- eases that cause impairment of wound healing. 3Y5 Researchers have been focused on accelerating the wound healing in diabetes by using topical and oral agents. 6,7 Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of depression and other psychiatric disorders. They down- regulate the postsynaptic A-receptors and serotonin receptors in the brain. 7 In recent years, studies have focused on the use of these agents on wound healing. Selective serotonin reuptake inhibitors were suggested as potential candidates for treatment of wounds because of their effects on interleukin and interferon (IFN) pro- duction as well as on increasing intracellular Ca +2 levels. 8Y10 Thus, paroxetine, as an SSRI, might affect the wound healing process ADVANCES IN SKIN & WOUND CARE & VOL. 27 NO.5 216 WWW.WOUNDCAREJOURNAL.COM ORIGINAL INVESTIGATION Esra Pancar Yuksel, MD, is Assistant Professor of Dermatology at the Department of Dermatology, Faculty of Medicine, Ondokuz Mayis University, Samson, Turkey. Fatih Ilkaya, MD, is Assistant Professor of Pharmacology at the Department of Pharmacology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. Levent Yildiz, MD, is Professor of Pathology at the Department of Pathology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. Fatma Aydin, MD, and Nilgun Senturk, MD, are Professors of Dermatology at the Department of Dermatology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. Hilal Denizli, MD, is a Resident in Dermatology at the Department of Dermatology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. Tayyar Canturk, MD, and Ahmet Yasar Turanli, MD, are Professors of Dermatology at the Department of Dermatology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. The authors have disclosed that they have no financial relationships related to this article. This study was supported by project number PYO.TIP.1901.12.020 by Ondokuz Mayis University. Submitted April 1, 2013; accepted in revised form August 16, 2013. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.