The Effect of Inhaled Ozone Therapy in Two-Hit Rat Model of Lipopolysaccharides-Induced Acute Lung Injury and Bleomycin-Induced Pulmonary Fibrosis

Considering the limited treatment options for acute lung injury (ALI) and pulmonary fibrosis (PF), ozone treatment may be promising as a new immunological agent with its ability to modulate cytokines and interferons. We aimed to investigate the effects of inhaled ozone therapy on both ALI and PF in rat models. A total of 48 albino Wistar male rats were included in the study. Lipopolysaccharide (LPS) was used to induce the ALI model, and bleomycin was used for the PF model. The effects of inhaled ozone (O3) were investigated using the ELISA method. Hematoxylin&eosin staining, Masson’s trichrome staining, and immunohistochemical methods were used for histopathological evaluation. The Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Nuclear Factor kappa B subunit p65 (NF-κB p65) levels in the ALI + 0.08 ppm O3, ALI + 0.12 ppm O3, PF + 0.08 ppm O3, and PF + 0.12 ppm O3 groups statistically decreased to the same extent and approached the levels of control animals. It was observed that IL-1β, IL-6, TNF-α, and NF-κB p65 levels in lung tissues were significantly and dose-dependently decreased compared to the untreated PF and ALI groups, respectively. While fibrosis was severe in the PF + 0.08 ppm O3 group, it decreased to more moderate levels in the PF + 0.12 ppm O3 group. The cytokine levels confirmed that inhaled ozone protected the lungs from both ALI and the development of PF. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.