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

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.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering

“…Furthermore, co-administration of Ok-PDRN and pirfenidone was found to alleviate the effects of acute respiratory distress syndrome in human lung epithelial cells, which was induced using a combination of LPS (1 μg/mL) and tissue growth factor-β (TGF-β) (5 ng/mL) [ 24 ]. This study demonstrated that PDRN inhibited the expression of basic fibroblast growth factor (FGF), collagen (COL) I, connective TGF, and hydroxyproline.…”

Could natural products modulate early inflammatory responses, preventing acute respiratory distress syndrome in COVID-19-confirmed patients?

“…Inhibition of collagen type I and fibroblast growth factor expressions. [ 43 ] Docosahexaenoic acids derived Resolvin D1 Mechanical stretch and acid-induced pulmonary fibrosis in mice and human lung epithelial (BEAS-2B) cells In vivo and in vitro Mice had the pulmonary fibrosis induced by intratracheal acid aspiration following mechanical ventilation for 24 h. Subsequently, mice were treated with resolvin D1 at 0.01, 0.1 and 1 μg for five consecutive days. Resolvin D1 at 0.01 nM/μL was used as pretreatment in BEAS-2B cells, which were exposed to acid for 10 min before being subjected to 48 h of mechanical stretch.…”

“…Although less usual, the use of animal-derived PANPs could also be an interesting approach for the treatment of mild respiratory and asthma-like symptoms in unhospitalized COVID-19 patients. A noteworthy example is the use of nucleotides from DNA blends [ 43 ]. Polydeoxyribonucleotide and pirfedidone were assessed against LPS and TGF-β-induced ARDS in human lung epithelial cells (A549).…”

“…Polydeoxyribonucleotide and pirfedidone were assessed against LPS and TGF-β-induced ARDS in human lung epithelial cells (A549). Hwang et al (2020) showed that the genetic material, individually or combined, were able to suppress TNF-α and IL-1β along with tissue growth factor [ 43 ].…”

Polydeoxyribonucleotide Attenuates Airway Inflammation Through A2AR Signaling Pathway in PM10-Exposed Mice

“…It has been reported that the increase in inflammatory factors can be reduced by adenosine A2A receptor (A2AR) stimulation in lung injury [9,10]. One of the adenosine agonists, polydeoxyribonucleotide (PDRN) is known as a candidate for anti-inflammatory drugs by inhibiting inflammation and apoptosis by selectively stimulating A2AR in lung-injured animals.…”