Int Neurourol J.  2020 May;24(Suppl 1):S56-64. 10.5213/inj.2040152.076.

Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells

Affiliations
  • 1Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
  • 2Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea
  • 3Department of Sport & Health Care, College of Art & Culture, Sangmyung University, Seoul, Korea
  • 4Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Korea
  • 5Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea

Abstract

Purpose
Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis.
Methods
The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed.
Results
In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β.
Conclusions
The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

Keyword

Acute respiratory distress syndrome; Polydeoxyribonucleotide; Pirfenidone, Combination therapy
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