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The Journal of Pharmacology and... Jan 2024Phosgene oxime (CX), categorized as a vesicating chemical threat agent, causes effects that resemble an urticant or nettle agent. CX is an emerging potential threat...
Phosgene oxime (CX), categorized as a vesicating chemical threat agent, causes effects that resemble an urticant or nettle agent. CX is an emerging potential threat agent that can be deployed alone or with other chemical threat agents to enhance their toxic effects. Studies on CX-induced skin toxicity, injury progression, and related biomarkers are largely unknown. To study the physiologic changes, skin clinical lesions and their progression, skin exposure of SKH-1 and C57BL/6 mice was carried out with vapor from 10 l CX for 0.5-minute or 1.0-minute durations using a designed exposure system for consistent CX vapor exposure. One-minute exposure caused sharp (SKH-1) or sustained (C57BL/6) decrease in respiratory and heart rate, leading to mortality in both mouse strains. Both exposures caused immediate blanching, erythema with erythematous ring (wheel) and edema, and an increase in skin bifold thickness. Necrosis was also observed in the 0.5-minute CX exposure group. Both mouse strains showed comparative skin clinical lesions upon CX exposure; however, skin bifold thickness and erythema remained elevated up to 14 days postexposure in SKH-1 mice but not in C57BL/6 mice. Our data suggest that CX causes immediate changes in the physiologic parameters and gross skin lesions resembling urticaria, which could involve mast cell activation and intense systemic toxicity. This novel study recorded and compared the progression of skin injury to establish clinical biomarkers of CX dermal exposure in both the sexes of two murine strains relevant for skin and systemic injury studies and therapeutic target identification. SIGNIFICANCE STATEMENT: Phosgene oxime (CX), categorized as a vesicating agent, is considered as a potent chemical weapon and is of high military and terrorist threat interest since it produces rapid onset of severe injury as an urticant. However, biomarkers of clinical relevance related to its toxicity and injury progression are not studied. Data from this study provide useful clinical markers of CX skin toxicity in mouse models using a reliable CX exposure system for future mechanistic and efficacy studies.
Topics: Animals; Mice; Phosgene; Disease Models, Animal; Mustard Gas; Mice, Inbred C57BL; Skin; Irritants; Erythema; Biomarkers; Oximes; Chemical Warfare Agents
PubMed: 37652710
DOI: 10.1124/jpet.123.001718 -
Environmental Science. Processes &... Jul 2023Sensing of gaseous environment pollutants and health hazards is in demand these days and in this regard, lethal phosgene has emerged as a leading entrant. In this...
Sensing of gaseous environment pollutants and health hazards is in demand these days and in this regard, lethal phosgene has emerged as a leading entrant. In this contribution, we have successfully developed a facile chemodosimeter (ANO) based on an anthracene fluorophore and oxime recognition site with an interesting mechanism to sense lethal phosgene evolved from bleaching powder, a very popular disinfectant and sanitizer. The ANO probe is highly competent in recognizing deadly phosgene in solution and in the gaseous phase with a detection limit in the nanomolar range (1.52 nM). The sensing mechanism is confirmed by UV-vis, emission spectroscopy, mass spectrometry, and computational studies.
Topics: Phosgene; Cost-Benefit Analysis; Spectrometry, Fluorescence; Gases; Fluorescent Dyes
PubMed: 37345355
DOI: 10.1039/d3em00171g -
Chemico-biological Interactions May 2024The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine,... (Review)
Review
The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated. The limited efficacy of current antidotes, known as AChE reactivators, pushes research towards new treatments. Numerous paths have been explored, from modifying the original pyridinium oximes to developing hybrid reactivators seeking a better affinity for the inhibited AChE. Another crucial approach resides in molecules more prone to cross the blood-brain barrier: uncharged compounds, bio-conjugated reactivators or innovative formulations. Our aim is to raise awareness on the threat and toxicity of organophosphorus nerve agents and to present the main synthetic efforts deployed since the first AChE reactivator, to tackle the task of efficiently treating victims of these chemical warfare agents.
Topics: Humans; Nerve Agents; Organophosphorus Compounds; Animals; Cholinesterase Reactivators; Medical Countermeasures; Acetylcholinesterase; Cholinesterase Inhibitors; Chemical Warfare Agents; Antidotes; Oximes
PubMed: 38574837
DOI: 10.1016/j.cbi.2024.110973