Colloids and Surfaces B: Biointerfaces 112 (2013) 499–507 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Investigation of the effects of local glutathione and chitosan administration on incisional oral mucosal wound healing in rabbits C ¸i˘ gdem Kılıc ¸ a , Emine Gülc ¸ eri Gülec ¸ Peker b , Füsun Acartürk c,∗ , Seda M. Sarı Kılıc ¸ aslan d , S ¸ ule C ¸ os ¸ kun Cevher b a Paragon Consultancy, Ankara, Turkey b Department of Biology, Faculty of Science, Gazi University, Ankara, Turkey c Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, Ankara, Turkey d Faculty of Education, Anadolu University, Eskis ¸ ehir, Turkey article info Article history: Received 16 April 2013 Received in revised form 4 August 2013 Accepted 30 August 2013 Available online 8 September 2013 Keywords: Glutathione Chitosan Wound healing Gingiva Antioxidant Oxidative stress Incision wound abstract The aim of the present study was to investigate the effects of local glutathione (GSH) and chitosan applica- tions on the oxidant events and histological changes that occur, during healing processes in rabbits with incisional intraoral mucosal wounds. For this purpose, discs containing glutathione and chitosan (1:1) were prepared and their physicochemical characteristics were evaluated. New Zealand white rabbits were used in in vivo studies. A standard incision was applied to the oral mucosa of rabbits. The rabbits were divided into four groups, being: an untreated incisional group (n = 6), a group treated with discs con- taining GSH + chitosan (n = 6), a group treated with discs containing solely chitosan (n = 5) and a group treated with discs containing solely GSH (n = 5). The levels of malondialdehyde (MDA), glutathione and nitric oxide (NOx) in the oral wound tissues were measured on the fifth day after the injury. Histological changes in the wound tissues were also investigated. The tissue MDA levels in the group treated with the disc containing GSH + chitosan were found to be lower than those in the other groups. There were no statistically significant differences in terms of tissue GSH and NOx levels between the group treated with the disc comprising GSH + chitosan and the control group that had untreated incision wounds. According to the histological findings, wound healing in the group treated with the disc containing solely chitosan was found to be better than in the other groups. The results of the experiments showed that the local application to the intraoral incision wounds of chitosan + GSH, and chitosan alone, can be effective in the wound healing processes of soft tissues and dental implants. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Wound healing is a process including phases of homeostasis, inflammation, proliferation and remodeling as well as many bio- chemical and cellular mechanisms [1,2]. Reactive oxygen species (ROS) are associated with all stages of the healing process. ROS are produced by the inflammatory cells and play an integral role during this process. Neutrophils and macrophages constitute most of the ROS sources. Increasing free oxygen radicals causes tissue necrosis and disruption of cellular integrity, and the severity of the oxidative damage depends on the balance of the antioxidant–oxidant system [2–4]. Antioxidant administration is beneficial for healing. Nitric oxide (NO) and superoxide (O 2- ) form the peroxynitrite (ONOO - ) radical and lead to lipid peroxidation, and malondialdehyde (MDA) is a relatively unchanged final product of lipid peroxidation. ∗ Corresponding author. Tel.: +90 3122139691; fax: +90 3122127958. E-mail addresses: acarturk@gazi.edu.tr, fusun.acarturk@gmail.com (F. Acartürk). Growth factors such as the epidermal growth factor (EGF), trans- forming growth factor beta (TGF-beta), and fibroblast growth factor (FGF) initiate the growth, differentiation, and metabolism of cells, and modulate the process of wound healing. During the wound healing phases, activated neutrophils and macrophages produce large amounts of superoxides, as well as its derivatives, via the phagocytic isoform of nicotinamide adenine dinucleotide phosphate oxidases. These strong oxidants contribute to oxidative damage in cells [2,4–6]. Glutathione (GSH) is a tripeptide composed of three different amino acids: glutamate, cysteine and glycine; it has numerous important functions within cells [7]. Glutathione plays roles in catalysis, metabolism, signal transduction, gene expression and apoptosis. It is the principal intracellular non-protein thiol and plays a major role in the maintenance of the intracellular redox states. Glutathione protects tissues by neutralizing free radicals [8,9]. In cases of damage in the oral cavity, decreases in GSH levels are observed while increases are observed in the oxidized glutathione 0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.08.050