Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury

Sci Rep. 2015 Mar 13:5:9072. doi: 10.1038/srep09072.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Botulinum Toxins, Type A / administration & dosage*
  • DNA Damage
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Hypoxia
  • Mice
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects
  • Protective Agents / administration & dosage*
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Skin / blood supply*
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin Ulcer / pathology
  • Skin Ulcer / prevention & control

Substances

  • Oxidants
  • Protective Agents
  • Reactive Oxygen Species
  • Botulinum Toxins, Type A