Mustard vesicant-induced lung injury: Advances in therapy

Toxicol Appl Pharmacol. 2016 Aug 15;305:1-11. doi: 10.1016/j.taap.2016.05.014. Epub 2016 May 19.

Abstract

Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.

Keywords: Fibrosis; Inflammatory mediators; Lung injury; Mustard gas; Therapeutic approaches; Vesicant.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemical Warfare Agents / toxicity*
  • Fibrin / metabolism
  • Humans
  • Irritants / toxicity*
  • Lung / drug effects
  • Lung / metabolism
  • Lung Injury / chemically induced*
  • Lung Injury / metabolism
  • Lung Injury / therapy*
  • Matrix Metalloproteinases / metabolism
  • Mesenchymal Stem Cells
  • Mustard Gas / toxicity*
  • RNA, Untranslated
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transient Receptor Potential Channels / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemical Warfare Agents
  • Irritants
  • RNA, Untranslated
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Transforming Growth Factor beta
  • Transient Receptor Potential Channels
  • Tumor Necrosis Factor-alpha
  • Fibrin
  • Matrix Metalloproteinases
  • Mustard Gas