stilbenes and ebselen

Modern-day high performance aircraft are more powerful, more efficient, and, unfortunately, frequently produce high noise levels, resulting in noise-induced hearing loss (NIHL) in military aircrew. Military pilots are required to perform many flight duties correctly in the midst of many challenges that may affect mission completion as well as aircraft and aircrew safety. NIHL can interfere with successful mission completion. NIHL may also require aircrew to be downgraded from flying duties, with the incumbent re-training costs for downgraded personnel and training costs for new/replacement aircrew. As it is not possible to control the source of the noise without compromising the efficiency of the engine and aircraft, protecting the aircrew from hazards of excessive noise and treating NIHL are of extreme importance. In this article we discuss various personal hearing protection devices and their efficacy, and pharmacological agents for prevention and management of NIHL.

Topics: Acetylcarnitine; Acetylcysteine; Aerospace Medicine; Aircraft; Anti-Inflammatory Agents; Antioxidants; Azoles; Creatine; Ear Protective Devices; Equipment Design; Excitatory Amino Acid Antagonists; Free Radical Scavengers; Genetic Therapy; Hair Cells, Auditory; Head Protective Devices; Hearing Loss, Noise-Induced; Humans; Hyperbaric Oxygenation; Isoindoles; Magnesium; Methionine; Military Personnel; Nanomedicine; Neuroprotective Agents; Organoselenium Compounds; Regeneration; Resveratrol; Salicylic Acid; Stilbenes; Vitamins

Vesicants are potent blistering agents. The prototype vesicant is sulphur mustard gas, first used in World War I, which still has no effective antidote. We used a mustard gas surrogate 2-chloroethyl ethyl sulphide (CEES) to study the ability of resveratrol (RES) and pterostilbene (PTS), two well-established stilbene antioxidants, ebselen (EB-1), an organoselenium compound, and three EB-1 analogues (EB-2, EB-3, and EB-4) to reduce CEES toxicity in human epidermoid carcinoma cells (A-431). Following a 24-hour incubation of a toxic concentration of CEES (1000 μmol L-1), we used the MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide] test to analyse cell viability. Different concentrations of test antioxidants alone (15 μmol L-1, 30 μmol L-1 or 60 μmol L-1) did not decrease cell viability. Treatment with CEES and test antioxidants for 24 h showed that only EB-1 and its analogues EB-2, EB-3, and EB-4 but not the stilbene compounds could rescue the cells from death. EB-1 and EB-4 were the most effective at reducing CEES cytotoxicity and did so in a concentration-dependent manner, while EB-2 and EB-3 demonstrated the least protective effect. In summary, the data described herein indicate that organoselenium antioxidants, especially EB-4, may prove useful as countermeasures to blistering agents.

Topics: Antioxidants; Azoles; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Chemical Warfare Agents; Humans; Isoindoles; Mustard Gas; Organoselenium Compounds; Oxidative Stress; Protective Agents; Resveratrol; Stilbenes

A series of test compounds were evaluated for an ability to reduce the toxicity of the nitrogen mustard mechlorethamine (HN2) in vitro. The test compounds included resveratrol, pterostilbene, vitamin C, ebselen, ebselen diselenide, and ebselen-sulfur. Among them, ebselen demonstrated the highest degree of protection against HN2 toxicity. To this end, pretreatment of the cells with ebselen offered protection against the toxicant whereas no protection was observed when cells were first incubated with HN2 and then treated with ebselen. Significant increases in caspase 3 and caspase 9 activities were observed in response to HN2, and ebselen was found to reduce these effects. Taken together, the data presented here indicate that ebselen is an effective countermeasure to nitrogen mustard in vitro, which is worthy of future investigation in vivo.

Topics: Antidotes; Antioxidants; Apoptosis; Ascorbic Acid; Azoles; Caspase 3; Caspase 9; Cell Line; Chemical Warfare Agents; Cytoprotection; Humans; Irritants; Isoindoles; Mechlorethamine; Organoselenium Compounds; Resveratrol; Stilbenes