Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model

Saito, Masao; Chen‐Yoshikawa, Toyofumi F.; Suetsugu, Kimitaka; Okabe, Ryo; Takahagi, A.; Masuda, Satohiro; Date, Hiroshi

doi:10.1016/j.jtcvs.2018.08.098

Cited by 39 publications

(27 citation statements)

References 29 publications

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“…Lung ischemia-reperfusion (I/R) injury can occur during many clinical events, such as lung transplantation, cardiopulmonary bypass, pulmonary embolism, single-lung ventilation, resuscitation for circulatory arrest, and shock, and can contribute to severe organ failure and increased mortality in patients ( Tejwani et al, 2016 ; Saito et al, 2019 ). Lung I/R injury is a complex pathological process that includes oxidative stress injury, the inflammation response, and cell apoptosis and is characterized by poor oxygenation, tissue edema, and neutrophil infiltration ( den Hengst et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway

et al. 2021

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Methane (CH4) exerted protective effects against lung ischemia-reperfusion (I/R) injury, but the mechanism remains unclear, especially the role of pulmonary surfactant. Therefore, this study aimed to explore the effects of CH4 inhalation on pulmonary surfactant in rat lung I/R injury and to elucidate the mechanism. Rats were randomly divided into three groups (n = 6): the sham, I/R control, and I/R CH4 groups. In the sham group, only thoracotomy was performed on the rats. In the I/R control and I/R CH4 groups, the rats underwent left hilum occlusion for 90 min, followed by reperfusion for 180 min and ventilation with O2 or 2.5% CH4, respectively. Compared with those of the sham group, the levels of large surfactant aggregates (LAs) in pulmonary surfactant, lung compliance, oxygenation decreased, the small surfactant aggregates (SAs), inflammatory response, oxidative stress injury, and cell apoptosis increased in the control group (P < 0.05). Compared to the control treatment, CH4 increased LA (0.42 ± 0.06 vs. 0.31 ± 0.09 mg/kg), oxygenation (201 ± 11 vs. 151 ± 14 mmHg), and lung compliance (16.8 ± 1.0 vs. 11.5 ± 1.3 ml/kg), as well as total antioxidant capacity and Nrf2 protein expression and decreased the inflammatory response and number of apoptotic cells (P < 0.05). In conclusion, CH4 inhalation decreased oxidative stress injury, inflammatory response, and cell apoptosis, and improved lung function through Nrf2-mediated pulmonary surfactant regulation in rat lung I/R injury.

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Section: Introductionmentioning

confidence: 99%

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway

et al. 2021

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“…Lung ischemia-reperfusion injury (LIRI) is one of the complications that can potentially arise after lung transplantation ( 1 ). Following lung transplantation, organ ischemia and subsequent reperfusion is unavoidable and frequently leads to acute sterile inflammation in a process known as ischemia reperfusion injury ( 1 , 2 ). LIRI may also develop into pulmonary infection, acute lung injury and bronchiolitis obliterans syndrome, thereby reducing the post-transplant survival rate and increasing risk of mortality ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Chen

Huang

2021

Exp Ther Med

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Lung ischemia-reperfusion injury (LIRI) is one of the complications that can occur after lung transplantation and may lead to morbidity and mortality. Mangiferin (MAF) is a naturally occurring glucosyl xanthone that has been documented to possess anti-inflammatory, immunomodulatory and potent antioxidant effects. The purpose of the present study was to investigate the effect of MAF on LIRI using a hypoxia-reoxygenation (H/R) cell model. In the present study, the viability of lung alveolar epithelial cells (A549) and H/R-A549 were detected by MTT assay. ELISA was used to evaluate the expression levels of IL-6 and IL-1β. TUNEL assay and western blotting were used to evaluate the apoptosis. In addition, H/R-A549 cells were treated with sirtinol, which is known inhibitor of sirtuin 1 (SIRT1) activity, to determine the effects of MAF on proteins associated with the SIRT1/5'AMP-activate protein kinase (AMPK) signaling pathway using western blotting. The results showed that 20 µM MAF exerted a protective effect on A549 cells against H/R mediating no clear cytotoxic effects. In terms of inflammation, MAF reduced IL-6, IL-1β, cyclooxygenase-2 and inducible nitric oxide synthase expression, which was accompanied by activation of the SIRT1/AMPK signaling pathway. In addition, compared with those in the group treated with sirtinol, expression of SIRT1, Bcl-2 and AMPK activity were elevated in MAF-treated H/R-A549 cells, whereas the expression of Bax, cleaved caspase-3 and cleaved caspase-9 was suppressed. TUNEL analysis of H/R-A549 cells treated with MAF in combination with sirtinol revealed that treatment with sirtinol blocked the SIRT1/AMPK signaling pathway and increased the apoptosis rate compared with the MAF group. Taken together, results of the present study revealed that MAF could inhibit lung H/R cell injury through the SIRT1/AMPK signaling pathway.

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“…Studies have shown that the pathogenesis of PIRI is complex, involving many pathophysiological processes and pathways, such as apoptosis (Wagner et al, 2006), autophagy , lymphocyte and macrophage infiltration (van der Kaaij et al, 2009) in oxidative stress injury (Yu et al, 2019), calcium overload (Li et al, 2015) and inflammatory injury (Krishnadasan et al, 2002). Therefore, many pharmacological agents involved in these pathophysiological processes and pathways were studied to alleviate PIRI, for instance, dexmedetomidine (Dex) (Liang et al, 2019), pirfenidone (Saito et al, 2019) and dexamethasone (Zhou et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine alleviates pulmonary ischemia-reperfusion injury through modulating the miR-21-5p/Nr4a1 signaling pathway

et al. 2020

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This study aims to investigate the protection of dexmedetomidine (Dex) against pulmonary ischemia-reperfusion injury (PIRI) in the mouse model and reveal the mechanism in hypoxia reoxygenation (H/R)-induced mouse pulmonary vascular endothelial cells (MPVECs). The lung wet-to-dry weight ratio, histopathological features, and malondialdehyde (MDA) concentrations were measured. The H/R-induced MPVECs were exposed to Dex, and the cell viability, cell apoptosis and protein expressions were assessed by the Cell Counting Kit-8 (CCK8) assay, flow cytometry and western blot, respectively. In addition, the regulatory relationship between miR-21-5p and orphan nuclear receptor 4A1 (Nr4a1) was revealed by several assays, including the dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. We found that the Dex treatment significantly alleviated pulmonary injury and decreased the level of MDA and wet/dry weight ratio in PIRI mice. Dex treatment also increased cell viability, reduced apoptotic ratio and downregulated expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 in H/R induced MPVECs. Furthermore, the expression of miR-21-5p was upregulated, while Nr4a1 was downregulated by Dex in a concentration-dependent manner in H/R induced MPVECs. Moreover, Nr4a1 was verified as a target of miR-497-5p. Overexpression of Nr4a1 could reverse the protective effects of Dex on alleviating H/R-induced injury in MPVECs. Taken together, Dex treatment attenuated ischemia-reperfusion induced pulmonary injury through modulating the miR-21-5p/Nr4a1 signaling pathway.

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Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model

Cited by 39 publications

References 29 publications

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Dexmedetomidine alleviates pulmonary ischemia-reperfusion injury through modulating the miR-21-5p/Nr4a1 signaling pathway

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