Adenosine A2A Receptor Agonist Polydeoxyribonucleotide Alleviates Interstitial Cystitis-Induced Voiding Dysfunction by Suppressing Inflammation and Apoptosis in Rats

Abstract

Background Interstitial cystitis (IC) is a chronic disorder that indicates bladder-related pain or discomfort. Patients with IC often experience urination problems, such as urinary frequency and urgency, along with pain or discomfort in the bladder area. Therefore, new treatments based on IC etiology are needed. Polydeoxyribonucleotide (PDRN) is a biologic agonist of the adenosine A 2A receptor, and PDRN has anti-inflammatory effect and inhibits apoptosis. In the current study, the effect of PDRN on cyclophosphamide-induced IC animal model was investigated using rats. Methodology To induce the IC animal model, 75 mg/kg of cyclophosphamide was injected intraperitoneally once every 3 days for 10 days. The rats in the PDRN-treated groups were intraperitoneally injected with 0.5 mL physiological saline containing 8 mg/kg PDRN, once a day for 10 days after IC induction. Results Induction of IC by cyclophosphamide injection caused voiding dysfunction, bladder edema, and histological damage. Cyclophosphamide injection increased secretion of pro-inflammatory cytokines and enhanced apoptosis. In contrast, PDRN treatment alleviated voiding dysfunction, bladder edema, and histological damage. Secretion of pro-inflammatory cytokines and expressions of apoptotic factors were suppressed by PDRN treatment. These changes indicate that treatment with PDRN improves voiding function by ultimately promoting the repair of damaged bladder tissue. Conclusion The conclusion of this experiment suggests the possibility that PDRN could be used as an effective therapeutic agent for IC.

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

“…However, confounding results exist regarding the influence of activation or suppression of P1 receptors, specifically adenosine receptor A2a, on inflammatory response and bladder overactivity. Yang et al reported that inhibition of adenosine A2a receptors with ZM241385, a selective A2a receptor antagonist, significantly alleviated bladder overactivity and hyperalgesia in CYP-treated animals by reducing the sensitivity of TRPV1 in DRG neurons [ 128 ], while Ko et al showed that activation of adenosine A2a receptor with polydeoxyribonucleotide (PDRN), an A2a receptor agonist, improved voiding dysfunction and reduced inflammation and apoptosis [ 129 ]. Interestingly, anti-inflammatory effects of PDRN have previously been demonstrated in animal models of various diseases, such as ischemic colitis, gastric ulcers, and Achilles tendon injury [ 130 , 131 , 132 ].…”

Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy

“…Previous papers have demonstrated that adenosine A 2Ar activation prevents ROS generation, also reducing inflammation and the apoptotic process [24,25]. PDRN, which is recognized as an A 2Ar agonist, showed several properties-including antioxidant, anti-apoptotic and anti-inflammatory ones-in several pre-clinical in vivo disease models, such as airway inflammation, cerebral ischemia, interstitial cystitis, acute lung injury, and ischemic colitis [26][27][28][29][30]. Moreover, a previous clinical trial demonstrated that PDRN eye drops stimulated corneal epithelium regeneration, thus supporting the hypothesis that it could be used for the treatment of corneal diseases [15,18].…”

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

“…Antiapoptotic Bcl-2 can inhibit the permeability changes of the outer mitochondrial membrane caused by Bax to prevent the release of cytochrome C into the cytoplasm, thereby inhibiting the occurrence of apoptosis [ 41 ]. In previous studies, it was found that CYP can cause urothelial cell apoptosis by upregulating the ratio of Bax/Bcl-2 [ 42 ]. Caspase-8 participates in apoptosis induced by the death receptor pathway [ 43 ].…”