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Mustard vesicant-induced lung injury: Advances in therapy

TitleMustard vesicant-induced lung injury: Advances in therapy
Publication TypeJournal Article
Year of Publication2016
AuthorsWeinberger B., Malaviya R., Sunil V.R, Venosa A., Heck D.E, Laskin J.D, Laskin D.L
JournalToxicol Appl Pharmacol
Date PublishedAug 15
ISBN Number0041-008X (Linking)
Accession Number27212445
Keywords*Fibrosis, *inflammatory mediators, *Lung injury, *Mustard Gas, *Therapeutic approaches, *Vesicant, Animals, Chemical Warfare Agents/*toxicity, Fibrin/metabolism, Humans, Irritants/*toxicity, Lung Injury/*chemically induced/metabolism/*therapy, Lung/drug effects/metabolism, Matrix Metalloproteinases/metabolism, Mesenchymal Stem Cells, Mustard Gas/*toxicity, Reactive Nitrogen Species/metabolism, Reactive Oxygen Species/metabolism, RNA, Untranslated, Transforming Growth Factor beta/metabolism, Transient Receptor Potential Channels/metabolism, Tumor Necrosis Factor-alpha/metabolism

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)-alpha 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.

Short TitleMustard vesicant-induced lung injury: Advances in therapy

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