Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

Abstract

Cadmium (Cd) impairs blood-testis barrier (BTB). Polydeoxyribonucleotide (PDRN), an adenosine A2A agonist, has positive effects on male reproductive system. We investigated the effects of PDRN on the morphological and functional changes induced by Cd in mice testes. Adult Swiss mice were divided into four groups: controls administered with 0.9% NaCl (1 ml/kg, i.p., daily) or with PDRN (8 mg/kg, i.p. daily), animals challenged with Cd chloride (CdCl2; 2 mg/kg, i.p, daily) and animals challenged with CdCl2 (2 mg/kg, i.p., daily) and treated with PDRN (8 mg/kg, i.p., daily). Experiments lasted 14 days. Testes were processed for biochemical, structural, and ultrastructural evaluation and hormones were assayed in serum. CdCl2 increased pERK 1/2 expression and Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels; it decreased testosterone (TE) and inhibin-B levels and induced structural damages in extratubular compartment and in seminiferous epithelium, with ultrastructural features of BTB disruption. Many TUNEL-positive germ cells were present. CdCl2 increased tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin, and N-cadherin immunoreactivity. PDRN administration reduced pERK 1/2 expression, FSH, and LH levels; it increased TE and inhibin-B levels, ameliorated germinal epithelium changes and protected BTB ultrastructure. Few TUNEL-positive germ cells were present and the extratubular compartment was preserved. Furthermore, PDRN decreased TGF-β3 immunoreactivity and enhanced claudin-11, occludin, and N-cadherin immunoreactivity. We demonstrate a protective effect of PDRN on Cd-induced damages of BTB and suggest that PDRN may play an important role against Cd, particularly against its harmful effects on gametogenesis.

Neuroprotective Effects of Polydeoxyribonucleotide in a Murine Model of Cadmium Toxicity

“…Therefore, the mechanism of Cd neurotoxicity should be better clarified, and measures should be taken to reduce Cd exposure in the general population to minimize the risk of adverse human health effects [ 46 ]. In this context, we previously demonstrated a positive effect of PDRN, an ADORA2A, which was demonstrated on Cd-induced damages of the blood-testis barrier, suggesting that it should also counteract the role of Cd as an endocrine disruptor [ 36 ].…”

“…A positive role of PDRN on Cd-induced structural changes of the blood-testis barrier was already demonstrated, suggesting that it may have a positive effect against Cd-induced structural lesions on gametogenesis [ 36 ].…”

Combined Treatment with Polynucleotides and Hyaluronic Acid Improves Tissue Repair in Experimental Colitis

“…Previous works from our laboratories [ 15 , 16 , 17 ] have demonstrated the anti-inflammatory and tissue repair activity of a A 2A receptor agonist, polydeoxyribonucleotide (PDRN), that contains a mixture of polynucleotides. To investigate the effects of a combined treatment with polynucleotides and hyaluronic acid in an experimental colitis setting, this mixture was employed to improve tissue remodelling and reduce inflammation.…”

A multidisciplinary experimental study on the effects of breeders diet on newborn seahorses (Hippocampus guttulatus)

“…Then, the tissues were dehydrated with increasing alcohol concentrations. The dehydrated pieces were embedded in Durcupan ACM (Squadrito et al, 2017). Finally, the sections were obtained with a Reichert Jung Ultracut E. Semi-thin sections (1 μm) were stained with toluidine blue and examined with a light microscope.…”