Polydeoxyribonucleotide Enhances Liver Regeneration Following Partial Hepatectomy in Rats in Association with Growth...

Background and Objectives: Liver regeneration following partial hepatectomy (PHx) is essential for restoring hepatic function. Polydeoxyribonucleotide (PDRN), an adenosine A_2A receptor (A_2AR) agonist, has demonstrated regenerative and proangiogenic properties in various tissues. However, its therapeutic potential for promoting liver regeneration after PHx has not been fully elucidated. The primary objective was to evaluate the effect of PDRN on liver regeneration after PHx, and the secondary objective was to examine associated changes in proliferation-related proteins and A_2AR/cAMP, HGF/c-Met, and VEGF/VEGFR2 signaling. Materials and Methods: A rat model of 70% PHx was established, and PDRN (8 mg/kg) was administered intraperitoneally once daily for 5 consecutive days with or without the A_2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 8 mg/kg). Liver regeneration was evaluated using biochemical, histological, and molecular analyses. Results: PDRN enhanced liver regeneration following PHx, as demonstrated by reduced serum liver enzyme levels, enhanced recovery of liver mass, and improved histological architecture. PDRN also increased the expression of the proliferation-associated proteins proliferating cell nuclear antigen (PCNA) and cyclin D1. These effects were accompanied by increased A_2AR expression and cyclic adenosine monophosphate (cAMP) levels, elevated hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels, and enhanced phosphorylation of c-Met and VEGFR2. Co-administration of DMPX attenuated the regenerative and molecular effects of PDRN, suggesting a potential involvement of A_2AR-related signaling. Conclusions: Collectively, these findings suggest that PDRN may facilitate liver regeneration following PHx in association with increased expression of proliferation-associated proteins and changes in HGF/c-Met and VEGF/VEGFR2 signaling, supporting its potential as a therapeutic strategy following hepatic resection.