title: Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction.
abstract: The diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation worldwide and is directly associated with comorbidity, disability and mortality. Oxidative stress mechanisms have been implicated in the pathogenesis of these wounds. Intra-lesional infiltration of epidermal growth factor has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. The aim of this study was to characterise the response of patients with DFUs to epidermal growth factor treatment in terms of redox status markers. Experimental groups included patients with DFUs before and 3-4 weeks after starting treatment with epidermal growth factor; compensated and non-compensated diabetic patients without ulcers; and age-matched non-diabetic subjects. Evaluations comprised serum levels of oxidative stress and antioxidant reserve markers. Patients with DFUs exhibited the most disheveled biochemical profile, with elevated oxidative stress and low antioxidant reserves, with respect to non-ulcerated diabetic patients and to non-diabetic subjects. Epidermal growth factor intra-lesional administration was associated with a significant recovery of oxidative stress and antioxidant reserve markers. Altogether, our results indicate that epidermal growth factor intra-ulcer therapy contributes to restore systemic redox balance in patients with DFUs.
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Ariana García
authors.initials: AG
authors.lastname: Ojalvo
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Jorge Berlanga
authors.initials: JB
authors.lastname: Acosta
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Yssel Mendoza
authors.initials: YM
authors.lastname: Marí
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Maday Fernández
authors.initials: MF
authors.lastname: Mayola
authors.affiliation: Diabetic Foot Ulcer Service, National Institute of Angiology and Vascular Surgery, Salvador Allende Hospital, Havana, Cuba.
authors.forename: Calixto Valdés
authors.initials: CV
authors.lastname: Pérez
authors.affiliation: Diabetic Foot Ulcer Service, National Institute of Angiology and Vascular Surgery, Salvador Allende Hospital, Havana, Cuba.
authors.forename: William Savigne
authors.initials: WS
authors.lastname: Gutiérrez
authors.affiliation: National Center for Integral Diabetes Care, Havana, Cuba.
authors.forename: Ileydis Iglesias
authors.initials: II
authors.lastname: Marichal
authors.affiliation: National Center for Integral Diabetes Care, Havana, Cuba.
authors.forename: Eduardo Álvarez
authors.initials: EÁ
authors.lastname: Seijas
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Alicia Molina
authors.initials: AM
authors.lastname: Kautzman
authors.affiliation: Wound Healing and Cytoprotection Group, Department of Pharmaceuticals, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Angélica Estrada
authors.initials: AE
authors.lastname: Pacheco
authors.affiliation: Southern Arizona Limb Salvage Alliance (SALSA), Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Armstrong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003462:Cuba; D017719:Diabetic Foot / Q000188:drug therapy*; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004815:Epidermal Growth Factor
keywords: Diabetes; Diabetes complications; Diabetic foot ulcers; Epidermal growth factor; Oxidative stress