Polydeoxyribonucleotide attenuates Lipopolysaccharide-induced Acute Lung Injury in Rats via modulation of the NF-?B and MAPK pathways

Abstract

Acute lung injury(ALI) induction upregulates tumor necrosis factor-α(TNF-α) that activates NF-κB and mitogen-activated protein kinases(MAPK) to induce pro-inflammatory mediators. Polydexyribonucleotide(PDRN) is an adenosine A2A receptor agonist, and it exerts anti-inflammatory effect by suppressing the production of pro-inflammatory cytokines, and suppressing apoptosis. We investigated the therapeutic efficiency of PDRN on ALI induced by lipopolysaccharide(LPS) in rats. Rats were randomly divided into 4 groups(n=8 each group): control, ALI-induced, ALI-induced and PDRN treated, ALI-induced and PDRN+3,7-dimethyl-1-propargylxanthine(adenosine A2A receptor antagonist; DMPX) treated. ALI was induced by intratracheal instillation of LPS(5mg/kg) in 200μL saline. Rats in drugs(PDRN, DMPX) treated groups received a single intraperitoneal injection of 500μL saline including PDRN(8mg/kg) and DMPX(8mg/kg), 1 h after lung injury induction. Rats were sacrificed 6h after PDRN and DMPX administrations, according to each group. Administration of LPS caused lung tissue damages, increased lung injury score and pro-inflammatory cytokines. Both NFκB and MAPK signaling factors were increased by LPS. However, PDRN therapy potently suppressed expressions of NFκB and MAPK signaling factors compared PDRN+DMPX treated group. These alterations led to a reduction of pro-inflammatory cytokines and NFκB and MAPK signaling, which promote recovery of damage pulmonary tissue. PDRN therapy showed more potent therapeutic effect on LPS-induced ALI compared to the non-treated and DMPX-treated group. Therefore, the PDRN may provide new therapeutic guideline for initial treatment in ALI.