Fluorofenidone attenuates paraquat‑induced pulmonary fibrosis by regulating the PI3K/Akt/mTOR signaling pathway and autophagy.

Abstract

Paraquat (PQ) is a widely used herbicide that is severely toxic to humans and animals. Pulmonary fibrosis is a disorder that can result from PQ poisoning. Fluorofenidone (AKF-PD) is a novel small molecule pyridone drug with a widespread and clear anti-organ fibrosis effect; however, its mechanism of action on PQ poisoning-induced pulmonary fibrosis is not clear. The purpose of the present study was to investigate the protective effect and underlying mechanism of AKF-PD on PQ poisoning-induced pulmonary fibrosis. Human alveolar epithelial cells (HPAEpiC) and Sprague-Dawley rats were treated with AKF-PD in the presence or absence of PQ. Hematoxylin-eosin and Masson staining were used to observe the morphological changes in lung tissue. Cell Counting Kit-8 and lactate dehydrogenase assays were used to evaluate the viability of HPAEpiC cells. ELISA was used to detect inflammatory factors and the collagen content. Finally, the effects of AKF-PD on pulmonary fibrosis, as well as the underlying mechanisms, were evaluated via western blotting, reverse transcription-quantitative PCR and immunofluorescence analysis. AKF-PD effectively alleviated PQ-induced pulmonary fibrosis and reduced the expression of oxidative stress and inflammatory factors. Moreover, AKF-PD treatment effectively inhibited the PI3K/Akt/mTOR signaling pathway and upregulated autophagy. Overall, these findings suggested that AKF-PD can alleviate PQ-induced inflammation and pulmonary fibrosis by inhibiting the PI3K/Akt/mTOR signaling pathway and by upregulating autophagy.