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Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2021 Jul; Vol. 96, pp. 107593. Date of Electronic Publication: 2021 Apr 02. - Publication Year :
- 2021
-
Abstract
- Background: Antioxidant and anti-inflammatory effects are two main pharmacological mechanisms of pirfenidone (PFD) besides the anti-fibrotic effect. This study aims to investigate whether PFD could mediate cigarette smoke extract (CSE) induced inflammation and oxidative stress in vitro and in vivo.<br />Methods: BALB/C mice and alveolar epithelial (A549) cells treated with CSE were established as disease models in vivo and in vitro. Effects of PFD treatment on disease models were further measured. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in lung tissues of mice. CCK-8 assay kit was applied to measure the viability of A549 cells treated by different concentrations of PFD. Inflammation cytokine expression in cell supernatants was measured with ELISA kits. The mRNA and protein levels of inflammation and oxidative stress-related factors were determined by real-time quantitative polymerase chain reaction analysis (RT-qPCR) and Western blotting. Furthermore, myeloperoxidase (MPO), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) were measured to detect the antioxidative activity of lung tissues. Moreover, an assay kit with fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH-DA) was used to evaluate the intracellular reactive oxygen species (ROS) generation.<br />Results: In vitro and in vivo, PFD significantly reversed TNF-α, IL-6, CCL2, SOD1, and CAT mRNA level changes led by CSE; in addition, PFD significantly decreased the ratios of p-p65 to p65, p-ikBα to ikBα and increased Nrf-2 protein level compared with CSE group. In mice, high-dose (100 mg/kg/d) PFD significantly reversed MPO and MDA increases induced by CSE. However, PFD didn't significantly reverse T-AOC decrease induced by CSE. In A549 cell supernatant, PFD dramatically reversed the elevated levels of TNF-α and IL-1β induced by CSE. Furthermore, PFD could significantly reverse the increased level of ROS induced by CSE in A549 cells.<br />Conclusion: Our study reveals the potential role of PFD in regulating inflammatory response and oxidative stress induced by CSE.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- A549 Cells
Animals
Cytokines metabolism
Humans
Inflammation chemically induced
Inflammation Mediators metabolism
Male
Mice
Mice, Inbred BALB C
Oxidative Stress
Plant Extracts administration & dosage
Reactive Oxygen Species metabolism
Respiratory Mucosa physiology
Signal Transduction
Anti-Inflammatory Agents therapeutic use
Cigarette Smoking adverse effects
Inflammation drug therapy
Lung pathology
Pyridones therapeutic use
Respiratory Mucosa drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33819731
- Full Text :
- https://doi.org/10.1016/j.intimp.2021.107593