Protective Effect of Polydeoxyribonucleotide Against Renal Ischemia-Reperfusion Injury in Mice

Jeong, Eui-Rim; Jang, Hyuk Jai; Kim, S.S.; Lee, S.Y.; Oh, Moon Young; Kim, H.J.; Eom, Dae-Woon; Ham, Jungyeob; Han, Duck Jong

doi:10.1016/j.transproceed.2016.01.028

Cited by 15 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies suggested that PDRN protects against testicular histological damage and markedly improves spermatogenesis, by increasing VEGF expression and angiogenesis, reducing inflammatory cascade and re-balancing the apoptotic machinery. The protective effect might be also ascribed to PDRN ability to limit ischemia reperfusion injury, as observed in the kidney (Jeong et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

View full text Add to dashboard Cite

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Furthermore, Muratsu et al (15) previously suggested that ZA enhances LPS-stimulated proinflammatory reactions in macrophages, with a consequent increase in LPS-induced apoptosis. PDRN has demonstrated effectiveness in decreasing the circulating levels of several inflammatory cytokines and increasing VEGF production in previous studies (20,21). The present study was therefore undertaken to analyze the effect of PDRN on RAW 264.7 cells pretreated with ZA and stimulated with LPS, by measuring inflammatory mediators.…”

Section: Discussionmentioning

confidence: 95%

“…Adenosine, a purine nucleoside, activates adenosine A 2A receptor and the stimulation of the receptor is suspected to decrease inflammatory cytokine secretion (16,18,19). Previous studies have demonstrated that PDRN significantly reduces the clinical signs of arthritis in mice, by decreasing the circulating levels of several inflammatory cytokines (20) and increasing vascular endothelial growth factor (VEGF) production, indicating decreased ischemic tissue damage and an enhanced oxygen supply (21). Ramanathan et al (22) also reported that the adenosine A 2A receptor and LPS increased VEGF expression through transcriptional regulation of the VEGF promoter.…”

Section: Anti-inflammatory Effect Of Polydeoxyribonucleotide On Zoledmentioning

confidence: 99%

Anti‑inflammatory effect of polydeoxyribonucleotide on zoledronic acid‑pretreated and lipopolysaccharide‑stimulated RAW 264.7 cells

et al. 2018

View full text Add to dashboard Cite

Bisphosphonates are generally used as therapeutic agents for bone diseases. However, previous reports on bisphosphonates-related osteonecrosis of the jaw (BRONJ) demonstrated that inflammation triggers and worsens the disease. Recently, polydeoxynucleotide (PDRN), an A receptor agonist, has been suggested for the treatment of various diseases and broadly studied for its anti-inflammatory effect. The present study aimed to measure the effect of PDRN on macrophage cells treated with zoledronic acid (ZA) and lipopolysaccharide (LPS). Macrophage cells were cultured with ZA for 24 h, following which they were stimulated with LPS in the presence or absence of varying concentrations of PDRN for 24 h. The cell viability and nitric oxide (NO) production of the cells were analyzed. In addition, protein expression levels were quantified by western blotting. Cell viability was compromised and NO was overexpressed by ZA and LPS stimulation. However, under ZA and LPS stimulation cell viability was enhanced, and NO production, and inducible nitric oxide synthase, interleukin (IL)-1β, -6, and tumor necrosis factor-α overexpression were suppressed on exposure to PDRN. A receptor and vascular endothelial growth factor (VEGF) expression levels increased following PDRN treatment. These results indicate that PDRN treatment of macrophages inhibits the inflammatory cytokines induced by ZA and LPS stimulation. It was hypothesized that the inflammatory cytokines were inhibited through A activation by PDRN. In addition, increased VEGF expression may contribute to increased vascularization and subsequently improve the pathological condition in BRONJ. As inflammation and LPS may stimulate the occurrence of BRONJ, the present study postulated that PDRN is possibly a candidate for the therapeutic management of BRONJ by decreasing inflammation and increasing vascularization.

show abstract

“…Polydeoxyribonucleotide is a DNA mixture with molecular weights ranging between 50 and 1,500 kDa, produced by regulated purification and sterilization processes from Oncorhynchus mykiss (salmon trout) or Oncorhynchus keta (chum salmon) sperm DNA (9). Multiple previous studies have demonstrated that classic PDRN is associated with tissue repair, in addition to anti-ischemia and anti-inflammation responses (26)(27)(28). In the present study, it was investigated whether a diverse range of DNAs may exert similar effects under pathophysiological conditions.…”

Section: Discussionmentioning

confidence: 99%

An effective range of polydeoxyribonucleotides is critical for wound healing quality

et al. 2018

View full text Add to dashboard Cite

Wound healing is a physiological restorative response to tissue and cell injury. This process occurs in collaboration with a complex cascade of cellular events, including biochemical alterations to the extracellular matrix. Polydeoxyribonucleotide (PDRN) is a fragmented DNA mixture from Oncorhynchus mykiss or Oncorhynchus keta sperm known to promote tissue regeneration under different pathophysiological conditions. However, the most effective molecular size of PDRNs for promoting the wound healing process and quality has not been established. In the present study, the regeneration quality with low (<50 kDa), middle [classic PDRN; 50-1,500 kDa] and high (>1,500 kDa) molecular weight PDRNs in a skin wound healing mouse model was examined using hematoxylin and eosin, as well as Masson's trichrome stain. A 4 mm biopsy punch was used to produce wounds in the skin of the mice. PDRN-mediated cellular behavior and signaling were evaluated by in vitro scratch assay and western blot analysis, respectively. It was observed that the apparent surface wound healing processes were not significantly different between PDRN molecular sizes. Immunohistochemical analysis revealed that classic PDRN-injected mice exhibited less lipid accumulation with increased collagen composition. These results suggested that 50-1,500 kDa PDRN offers an effective DNA mixture to improve wound healing quality. Furthermore, classic PDRN increased cell migration via c-Jun N-terminal kinase signaling in human fibroblasts. The present study suggests an optimal PDRN molecular weight to promote wound healing, and novel approaches for therapeutic strategies to improve tissue regeneration quality.

show abstract

Protective Effect of Polydeoxyribonucleotide Against Renal Ischemia-Reperfusion Injury in Mice

Cited by 15 publications

References 23 publications

Pharmacological Activity and Clinical Use of PDRN

Pharmacological Activity and Clinical Use of PDRN

Anti‑inflammatory effect of polydeoxyribonucleotide on zoledronic acid‑pretreated and lipopolysaccharide‑stimulated RAW 264.7 cells

An effective range of polydeoxyribonucleotides is critical for wound healing quality

Contact Info

Product

Resources

About