Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats

Aim: To demonstrate the possible protective efficacy of nintedanib, a tyrosine kinase inhibitor with demonstrated antifibrotic and antitumor activity, in a model of acute lung injury (ALI), a severe lung disease, through NLR family pyrin domain containing 3 (NLRP3) and nuclear factor kappa B (NF-kappa B) pathways. Materials and Methods: In this study, 40 male Wistar albino rats were used. These rats were divided into 5 groups of equal sizes. Before the experiment began, nintedanib was administered orally to selected groups at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg. At 24 hours, 12 hours, or 1 hour after nintedanib administration, rats selected for the lung injury model were administered intratracheal LPS. Interleukin (IL)-1 beta and tumor necrosis factor-alpha (TNF-alpha) amounts were measured by ELISA method and NLRP3, caspase-1, IL-1 beta and NF-kB gene expressions were measured by reverse-transcriptase polymerase chain reaction. Results: It was observed that administration of nintedanib lowered the elevated NLRP3, caspase-1, IL-1 beta, and NF-kappa B expressions and the IL-1 beta and TNF-alpha cytokine levels in the tissues of rats with LPS-induced ALI. The findings obtained for the rats included in the lung injury group that received 50 mg/kg nintedanib were most similar to those of the healthy control group. Conclusion: In rats modeled with ALI, nintedanib was shown to modulate the NLRP3/NF-kappa B signaling pathway and reduce the effects of ALI.