title: In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.
abstract: Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects.
authors.affiliation: Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey. Electronic address: dbagdas@uludag.edu.tr.
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.affiliation: Department of Physiology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Betul Cam
authors.initials: BC
authors.lastname: Etoz
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Zulfiye
authors.initials: Z
authors.lastname: Gul
authors.affiliation: Department of Biology, Faculty of Science and Arts, Uludag University, Bursa, Turkey.
authors.forename: Sedef
authors.initials: S
authors.lastname: Ziyanok
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: Sevda
authors.initials: S
authors.lastname: Inan
authors.affiliation: Department of Biology, Faculty of Science and Arts, Uludag University, Bursa, Turkey.
authors.forename: Ozge
authors.initials: O
authors.lastname: Turacozen
authors.affiliation: Department of Surgery, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: Nihal Yasar
authors.initials: NY
authors.lastname: Gul
authors.affiliation: Department of Surgery, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Topal
authors.affiliation: Department of Biology, Faculty of Science and Arts, Uludag University, Bursa, Turkey.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Cinkilic
authors.affiliation: Department of Biology, Faculty of Science and Arts, Uludag University, Bursa, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Tas
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: Musa Ozgur
authors.initials: MO
authors.lastname: Ozyigit
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Mine Sibel
authors.initials: MS
authors.lastname: Gurun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002726:Chlorogenic Acid / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D009569:Nitric Oxide; D008315:Malondialdehyde; D013311:Streptozocin; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D006909:Hydroxyproline
keywords: Antioxidant; Chlorogenic acid; Cytotoxicity; Diabetic wound healing; Genotoxicity; Oxidative stress