https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1136&context=usarmyresearch

Inflammatory effects of inhaled sulfur mustard in rat lung

Airway instillation into rats of 2-chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co-instillation with CEES of liposomes containing pegylated (PEG)-catalase (CAT), PEG-superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co-instillation of liposomes containing the reducing agents, N-acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti-oxidant compounds maximally attenuated CEES-induced lung injury by nearly 80%. Delayed airway instillation of anti-oxidant-containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes.

/pdf/attenuation-of-half-sulfur-mustard-gas-induced-acute-lung-v32x75abt5.pdf

Attenuation of half sulfur mustard gas-induced acute lung injury in rats.

Exposure to liquid sulfur mustard.

Possible immediate and long-term health effects following exposure to chemical warfare agents.

Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.

Sulfur mustard and respiratory diseases.

In 1984 and 1985, a total of eleven Iranian patients were transferred to hospitals in Munich, Germany, after a reported gas attack in the Iran-Iraq war. The initial symptoms and pretreatment in Teheran, Iran, as well as the admittance examination data, the clinical courses of the patients, and the clinical laboratory data in Germany, are reported. The main injuries were to the skin, the eyes, and the respiratory tract. One patient stopped breathing suddenly on the third day of treatment (eight days after the exposure). A large piece of mucous membrane blocking a bronchus was removed during an immediate bronchoscopy, but attempts at resuscitation failed. The most important autopsy findings in this case were severe pseudomembranous inflammation of the trachea and the bronchial tubes. The histological findings are reported. Chemical proof of the poison (mustard gas) was established. A review of the history of chemical warfare, the physical and chemical properties of mustard gas, and a literature survey of clinical findings (including, especially, experiences from World Wars I and II) contribute to the understanding of the actual cases.

/pdf/clinical-and-morphological-findings-on-mustard-gas-bis-2-55y44ze98h.pdf

E Kretschmer

Papers

Clinical and morphological findings on mustard gas [bis(2-chloroethyl)sulfide] poisoning.