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Understanding the Mechanism of Nitrogen Mustard-an Analog of a Chemical Warfare Agent Induced Skin Injuries
José Antonio Arellano, MD1, Yusuf Surucu, MD1, Vincent Nerone, BA1, Katherine S. Yang, BS1, Alexey V. Altman1, Rakib ul Islam1, Zayaan Trimzi1, Baris Bengur, MD; Shawn Loder, MD; Jeffrey A. Gusenoff, MD; Francesco Egro1, Asim Ejaz, PhD1
UPMC
2023-01-29
Presenter: José Antonio Arellano
Affidavit:
Peter J. Rubin
Director Name: Peter J. Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction: Alkalizing weaponizable agents have been used in combat situations or terrorism throughout history, yet the mechanism of injury has not been fully explained. Currently there are no reliable model system available having translational potential to humans. We use a novel system of perfused human tissue as a model to induce an insult with an analog of sulfur mustard and study the pathways of the injury in the skin and treatments.
Methods: We use a tissue sample from a dermolipectomy and perfuse it with a special culture media controlling the oxygen and carbon dioxide, pressure, and temperature. We applied to the skin 10mg/cm2 of nitrogen mustard and as acetone was applied as control. Punch biopsies were taken periodically, and they were stained for H&E and TUNNEL (apoptosis). Inflammation, apoptosis, and cell survival associated gene expression was analyzed.
Results: The H&E staining showed that in the nitrogen mustard-induced injury skin had epithelial spongiosis, pyknosis, and vacuoles in keratinocytes. The control group shows minimum damage and changes in cell death or irreversible damage. Tunnel staining showed an increase in cell death of keratinocytes in nitrogen mustard compared to the control. We observed a significant decrease in the anti-apoptotic and pro-survival gene expression in NM treated skin.
Conclusion: Our perfused model of human tissue shows novel preliminary data that can be used to understand the mechanism of cell death and understand the natural course of injury of chemical weapons and provide possible treatments.
