Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model

Masao Saito, Toyofumi F. Chen-Yoshikawa, Kimitaka Suetsugu, Ryo Okabe, Akihiro Takahagi, Satohiro Masuda, Hiroshi Date

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Objective: Lung ischemia-reperfusion injury is among the complications seen after lung transplantation, resulting in morbidity and mortality. Pirfenidone, an antifibrotic agent for the treatment of idiopathic pulmonary fibrosis, is reported to have cytoprotective properties in various disease models. The purpose of this study was to investigate the effect of pirfenidone on lung ischemia-reperfusion injury. Methods: Male Lewis rats (260-290 g) were divided into 3 groups: sham group (n = 5), warm ischemia (WI) group (n = 10), and WI plus pirfenidone (WI+PFD) group (n = 10). The sham group underwent 210 minutes of perfusion without ischemia. The WI and WI+PFD groups underwent 90 minutes of warm ischemia and 120 minutes of reperfusion. In the WI+PFD group, pirfenidone (300 mg/kg) was administered orally by gavage 30 minutes before ischemia. After reperfusion, arterial blood gas analysis, lung mechanics, lung wet-to-dry weight ratio, and histologic findings were obtained. The gene expressions of proinflammatory cytokines in lung tissue were measured by quantitative reverse transcription polymerase chain reaction. Results: Compared with the WI group, the WI+PFD group had significantly better dynamic pulmonary compliance (P <.01) and oxygenation levels (P <.05). The wet-to-dry ratio was lower in the WI+PFD group (P <.05). Histologic analysis showed that the WI+PFD group had reduced perivascular edema and neutrophil infiltration. The expression of tumor necrosis factor-α messenger RNA was decreased in the WI+PFD group (P <.05). Conclusions: Our results revealed that in a rat hilar clamp model, pirfenidone alleviated lung ischemia-reperfusion through anti-inflammatory effects.

Original languageEnglish
Pages (from-to)289-296
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number1
Publication statusPublished - Jul 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model'. Together they form a unique fingerprint.

Cite this