Molecular Strategies Against Sulfur Mustard Toxicity
GULHANE MILITARY MEDICAL ACADEMY ANKARA (TURKEY) DEPT OF NBC DEFENSE
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Among the available chemical warfare agents, sulfur mustard SM, also known as mustard gas, has been a widely used chemical weapon. Because of its devastating toxicity, its use during the World War I earned it the sobriquet king of the battle gasses . The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. In our laboratory, we have shown that, acute toxicity of SM is related to reactive oxygen and nitrogen species, DNA damage, polyADP-ribose polymerase activation and energy depletion within the affected cell. Therefore, a variety of antioxidant molecules including N-acetyl cysteine, alpha-tocopherol, and melatonin may exert beneficial effects against acute mustard-induced toxicity. Because excess nitric oxide and peroxynitrite also involve in the pathogenesis of SM-induced toxicity inhibitors of nitric oxide synthase e.g., aminoguanidine, and peroxynitrite scavengers e.g., ebselen may also alleviate the chemical damage. In spite of the knowledge about acute SM-induced cellular toxicity, unfortunately, it is not clear how mustard gas causes severe multi-organ damage years after even a single exposure. Because of difficulties to create delayed toxicity of SM experimentally, we have almost no idea about the efficacy of molecules used against acute SM-induced toxicity. Nevertheless, 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. A variety of treatment modalities including antioxidants, anti-inflammatory drugs and others have resulted no promising results. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Chemical, Biological and Radiological Warfare