Lethal concentration of perfluoroisobutylene induces acute lung injury in mice mediated via cytokine storm, oxidative stress and apoptosis

Abstract

Perfluoroisobutylene (PFIB) is a highly toxic gas that targets the lungs. Low-level inhalation of the gas can lead to acute lung injury (ALI), pulmonary edema and even death. No specific anti-PFIB drugs are currently available and the pathogenesis of PFIB-induced ALI is not fully understood. Early direct oxidative injury and a secondary hyper-inflammatory response are recognized as the primary mechanisms of PFIB-induced ALI. In the present study, our data demonstrate for the first time that a cytokine storm is associated with PFIB-induced ALI. Levels of 10 pro-inflammatory cytokines and one anti-inflammatory cytokine were significantly increased in lung tissues of PFIB-exposed mice. PFIB inhalation additionally led to significant oxidative stress in lung tissue. Inflammation-associated CD11bLy6GLy6C neutrophils and CD11bLy6GLy6C monocytes were significantly increased in blood in association with PFIB-induced ALI. Bcl-2/Bax-mediated lung cell apoptosis was significantly increased at 1 h, followed by a sustained decrease after 1 h, which was significant at 4-8 h in PFIB-exposed mice. This suppression of apoptosis is possibly associated with the Akt-signaling pathway.

Perfluoroisobutene: Poisonous Choking Gas

“…ALI remains a significant source of morbidity and mortality in the critically ill patient population. Higher doses cause pulmonary edema with wheezing, difficulty in breathing, coughing up sputum and bluish discoloration of the skin (Brubaker, 1977;Zhang et al, 2017). PFIB toxicity is similar to that of other fluorolefins.…”

Apoptotic mechanisms in rabbits with blast-induced acute lung injury

“…Introduction Acute lung injury (ALI), as a cause of death in explosive blast casualties 1 , is a complex clinical syndrome involving acute inflammation, microvascular damage, and increased pulmonary vascular and epithelial permeability, which results in fatal acute respiratory distress syndrome (ARDS) 2 . ARDS refers to a complex pathological process caused by direct/indirect injury to the body, including assisted ventilation 3 , blood transfusion 4 , inflammation 5 , severe trauma or sepsis 6 , drowning or blast 7 , and even toxins 8 . Currently, the most widely accepted definition of ALI/ARDS is based on the American-European Consensus Conference definition of acute onset respiratory failure with bilateral infiltrates on chest radiograph and pulmonary capillary wedge pressure <18 mmHg or absence of elevated left atrial pressure 9 , which leads to injury in alveolar epithelial cells and capillary endothelial cells.…”

Pulmonotoxicyty of Synthetic Polymers Combustion Products

“…Спектр химических соединений, образующихся в результате горения твердых горючих материалов, не всегда определен, тем не менее можно выделить следующие группы токсичных веществ: общеядовитого (оксид углерода, цианиды, эпихлоргидрин) [2], пульмонотоксического (хлороводород, фосген, фтороводород) [11,20,35], цитотоксического (полихлорированные дибензо-n-оксины и дибензофураны) [24] и раздражающего (акролеин, формальдегид, ацетальдегид) [21,30] Помимо хлорсодержащих полимеров широкое применение в деятельности человека находят фторсодержащие материалы. Применение фторированных полимеров обусловлено их более высокой термостабильностью по сравнению с соот-ветствующими им углеводородными аналогами.…”

“…Примером фторсодержащих полимеров служит политетрафторэтилен (тефлон). При температуре горения, превышающей 380 °С, тефлон разрушается до высокотоксичного перфторизобутилена и фтористого водорода [35].…”

“…Аналогичным механизмом действия обладает фтороводород. Его водный раствор, плавиковая (фтороводородная) кислота, оказывает выраженное прижигающее действие на слизистые оболочки дыхательных путей, что также может приводить к развитию токсического отека легких [35].…”