OZONE THERAPY AMELIORATES LPS-INDUCED ACUTE LUNG INJURY IN MICE BY INHIBITING THE NLRP3/ASC/CASPASE-1 AXIS.

Abstract: Background: Acute lung injury (ALI) is a common respiratory emergency with high incidence and mortality. Among its main pathologic mechanisms is the rapid and intense inflammatory response. Ozone is a naturally occurring compound and is known for its properties as an oxidizing agent. Ozone therapy is the clinical application of a mixture of ozone (O 3 ) and oxygen, used within nontoxic, safe concentrations. It could be used for the treatment of several diseases. Ozone rectal insufflation (O 3 -RI) is a treatment in which medical O 3 is introduced into the rectum to treat and prevent disease. Although O 3 therapy exerts anti-inflammatory effects, its function in ALI remains unclear. The aim of this study was to preliminarily investigate the role and function of O 3 -RI in ALI. Methods: A mouse model of ALI was established by intratracheal administration of LPS. O 3 -RI was administered 4 h following the modeling procedure. Lung histopathology, lung wet/dry ratio, protein content in bronchoalveolar lavage fluid (BALF), and myeloperoxidase activity in lung tissues, as well as the number of inflammatory cells and inflammatory cytokines in BALF, were assessed. The expression levels of NOD-like receptor thermal protein domain associated protein (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis-related proteins in lung tissues were examined by real-time fluorescence quantitative polymerase chain reaction and Western blotting. Results: Ozone therapy reduced the wet/dry ratio of lung tissue and total protein content in BALF and attenuated lung edema and microvascular leakage in ALI mice. Ozone therapy reduced the myeloperoxidase content in the lung tissue, the number of inflammatory cells, and the content of inflammatory cytokines in BALF and attenuated lung tissue inflammation in mice with ALI. Ozone therapy ameliorated lung tissue morphological damage in ALI mice. Ozone therapy downregulated the expression of NLRP3/ASC/caspase-1 axis-related proteins. Conclusion: Ozone therapy attenuated LPS-induced ALI in mice, possibly by inhibiting NLRP3/ASC/caspase-1 axis. Ozone therapy is a valuable potential therapeutic modality for ALI.