title: Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury.
abstract: Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the synaptic space, and has been clinically used for aesthetic indications, neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that BTX-A enhanced the blood flow and improved ischemia in animal models. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The number of CD31(+) vessels and αSMA(+) pericytes or myofibroblasts in wounds were significantly increased in the I/R mice treated with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. In an in vitro assay, BTX-A significantly prevented the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in vascular endothelial cells. Furthermore, the administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. Exogenous application of BTX-A might have therapeutic potential for cutaneous I/R injuries.
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Uchiyama
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Buddhini
authors.initials: B
authors.lastname: Perera
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Sei-Ichiro
authors.initials: S
authors.lastname: Motegi
mesh_terms: D000818:Animals; D017209:Apoptosis; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D004249:DNA Damage; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000860:Hypoxia; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012883:Skin Ulcer / Q000473:pathology / Q000517:prevention & control
chemical_list: D016877:Oxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D019274:Botulinum Toxins, Type A