title: Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing.
abstract: Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti-inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing.
authors.affiliation: Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey, dbagdas@uludag.edu.tr.
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.forename: Nihal Yasar
authors.initials: NY
authors.lastname: Gul
authors.forename: Ayse
authors.initials: A
authors.lastname: Topal
authors.forename: Sibel
authors.initials: S
authors.lastname: Tas
authors.forename: Musa Ozgur
authors.initials: MO
authors.lastname: Ozyigit
authors.forename: Nilufer
authors.initials: N
authors.lastname: Cinkilic
authors.forename: Zulfiye
authors.initials: Z
authors.lastname: Gul
authors.forename: Betul Cam
authors.initials: BC
authors.lastname: Etoz
authors.forename: Sedef
authors.initials: S
authors.lastname: Ziyanok
authors.forename: Sevda
authors.initials: S
authors.lastname: Inan
authors.forename: Ozge
authors.initials: O
authors.lastname: Turacozen
authors.forename: Mine Sibel
authors.initials: MS
authors.lastname: Gurun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D002726:Chlorogenic Acid; D009569:Nitric Oxide