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Fluorofenidone attenuates paraquat‑induced pulmonary fibrosis by regulating the PI3K/Akt/mTOR signaling pathway and autophagy.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2021 Jun; Vol. 23 (6). Date of Electronic Publication: 2021 Mar 31. - Publication Year :
- 2021
-
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.
- Subjects :
- Alveolar Epithelial Cells drug effects
Alveolar Epithelial Cells metabolism
Animals
Cells, Cultured
Humans
Male
Oxidative Stress
Paraquat toxicity
Proto-Oncogene Proteins c-akt metabolism
Pulmonary Fibrosis etiology
Pulmonary Fibrosis metabolism
Pyridones pharmacology
Rats
Rats, Sprague-Dawley
TOR Serine-Threonine Kinases metabolism
Autophagy
Phosphatidylinositol 3-Kinases metabolism
Pulmonary Fibrosis drug therapy
Pyridones therapeutic use
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 23
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 33786626
- Full Text :
- https://doi.org/10.3892/mmr.2021.12044