Dynamics of aquaporin content in the aero-hematic barrier during the latent phase of toxic pulmonary edema

Abstract

The study evaluates the dynamics of aquaporin (aquaporin-1, aquaporin-5, and epithelial sodium channel) content in the aero-hematic barrier during the latent phase of rat intoxication with carbonyl chloride (phosgene), thermal decomposition products of fluoroplast containing perfluoroisobutylene, and nitrogen dioxide. Rat intoxication was modeled using average lethal concentrations of these toxic substances. At 30 and 60 minutes post-exposure, pulmonary coefficient was measured and histological and immunohistochemical studies were performed. Western blot analysis was used to determine the aquaporin-5 content in rat lung tissues exposed to the thermal decomposition products of fluoroplast. It was found that rat intoxication with phosgene and thermal decomposition products of fluoroplast containing perfluoroisobutylene led to an increase in the relative content of aquaporin-5 and epithelial sodium channel-positive cells in lung tissues as early as 30 minutes post-exposure. At 60 minutes post-exposure, there were signs of the interstitial phase of toxic pulmonary edema and an increase in the pulmonary coefficient. Exposure to nitrogen dioxide resulted in an increase in the pulmonary coefficient and the relative content of aquaporin-5-positive cells, as well as pronounced signs of the interstitial phase of edema 30 minutes post-exposure. Western blot analysis using anti-aquaporin-5 antibodies revealed an increase in the staining intensity of complexes with molecular weights of 25 and 50 kDa, suggesting the formation of aquaporin-5 tetramers and their likely translocation from the intracellular compartment to the plasma membrane of alveolar cells. These findings indicate that aquaporin-5 plays an important role in the pathogenesis of toxic pulmonary edema induced by the studied pneumotoxicants. Targeting these molecules may be a promising approach for pathogenetic therapy of poisoning.

Keywords

aquaporin-1 / aquaporin-5 / nitrogen dioxide / immunohistochemistry / intoxication / carbonyl chloride (phosgene) / perfluoroisobutylene / toxic pulmonary edema / epithelial sodium channel

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