Газоподібний хлор: молекулярні механізми токсичності, клінічні прояви, діагностичні біомаркери та сучасна лікувальна стратегія

Abstract

The hostilities on the territory of our state are accompanied by the destruction of the infrastructure of cities and industrial enterprises, which critically increased the risk of toxic gas emissions (including chlorine) and the occurrence of mass poisoning. Aim. To summarize modern knowledge about the molecular mechanisms of chlorine gas toxicity, clinical biomarkers of the toxic process, and modern treatment strategy. Material and Methods. Information data of the Ministry of Health of Ukraine, the State Emergency Service of Ukraine (SES of Ukraine), the American Health Service (CDC), the American Association of Poison Control Centers (AAPCC), materials of scientific libraries PubMed, Medline, Elsevier. Content analysis, systematic and comparative analysis were used. Results and their Discussion. Chemical accidents with the release of chlorine and the occurrence of mass poisonings are registered in various countries. Until now, the mechanisms of the toxic action of chlorine remain completely unstudied, especially at the level of intracellular structures. The results of recent studies demonstrate that irritant and irritant-necrotic effects are not directly caused by chlorine molecules, but by their hydration products – hydrochloric and hypochlorous acids. These acids directly provide a high production of reactive superoxides and nitrogen oxidants, which form oxidative stress in the epithelial cells of the mucous membrane of the bronchopulmonary structure in deeper tissues. The destruction of the cells of the ciliated epithelium occurs, the functioning of ion channels is disturbed and the permeability of cell membranes increases, inflammatory reactions develop: hyperemia, edema, bronchospasm, and surfactant destruction. These processes are facilitated by a massive release of biologically active substances – proinflammatory cytokines – IL-1β, IL-6, IL-18, nuclear factor (NF-KB), 8-isoprostane and tumor necrosis factor (TNF-β) – one of the main biomarkers of oxidative stress. These processes cause: damage to intracellular structures – mitochondria; imbalance in the functioning of the signaling molecule cAMP and disruption of autophagy processes; a decrease in the energy potential of cells with the development of endothelial dysfunction, a violation of the vascular mechanisms of NO homeostasis, both in the cells of the respiratory tract and outside the lungs, which contributes to anatomical damage and impaired function of the organs of the cardiovascular system and kidneys. Conclusion. The mechanism of the toxic action of chlorine at the level of intracellular structures undoubtedly requires further study. Another relevant direction of research may be the search for new sensitive biomarkers of the toxic process, which will allow us to objectively assess the severity of poisoning and increase the effectiveness of the rather complex process of treating patients, in the absence of antidotes. Key Words: chlorine gas, toxicity, mechanism of action, acute poisoning, treatment of poisoning.