Mustard vesicant-induced lung injury: Advances in therapy

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• 作者：Barry Weinberger^a ; ^{bweinberger@northwell.edu" class="auth_mail" title="E-mail the corresponding author} ; Rama Malaviya^b ; Vasanthi R. Sunil^b ; Alessandro Venosa^b ; Diane E. Heck^c ; Jeffrey D. Laskin^d ; Debra L. Laskin^b
• 关键词：Mustard gas ; Vesicant ; Lung injury ; Fibrosis ; Inflammatory mediators ; Therapeutic approaches
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：305
• 期：Complete
• 页码：1-11
• 全文大小：779 K

文摘

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.