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

Abstract

Inflammatory bowel diseases (IBDs) are chronic conditions that can benefit from the combined treatment of adenosine receptor agonists and hyaluronic acid (HA), which, binding the CD44, has pro-survival effects. Therefore, this study investigated the effects of a mixture of polynucleotides and HA in an experimental model of dinitrobenzenesulfonic acid (DNBS)-induced colitis. A group of 40 rats received a single intra-colonic instillation of DNBS, and after 6 h, animals were randomized to receive daily: (i) saline solution; (ii) polynucleotides (Poly; 8 mg/kg); (iii) polynucleotides (8 mg/kg) plus hyaluronic acid (HA; 15 mg/kg); and (iv) hyaluronic acid (HA; 15 mg/kg). Rats in the control group (n = 10) received saline solution only. Seven days after induction, animals receiving Poly plus HA showed reduced clinical signs, weight loss and colon shortening, ameliorated macroscopic and histological damage, and apoptosis. Moreover, the combined treatment reduced the positivity in the colonic infiltrate of CD3 positive T cells, CD20 positive B cells and CD44. Furthermore, Poly plus HA reduced colonic myeloperoxidase activity and malondialdehyde, indicating a dampening of the inflammatory infiltrate and oxidation products. Our research demonstrated that a combined treatment of polynucleotides with hyaluronic acid had a protective effect in a model of ulcerative colitis, suggesting that this association deserves further attention for the treatment of IBDs.

NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele

“…Primary antibody (caspase-1, 1:250, Cell Signalling, Tucson, AZ, USA) was incubated overnight at 4 °C in a moisturized chamber and the day after the secondary antibody (anti-mouse, Vectastain, Vector, Burlingame, CA, USA) was added and the reaction was visualized with 3,3′-Diaminobenzidine (DAB) (Sigma-Aldrich, Milan, Italy). Counterstaining was performed in Mayer’s haematoxylin [ 67 ]. Appropriate positive and negative controls were used in each test.…”

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering

“…Four studies assessed the potential of Ok- and Om-PDRNs as anti-inflammatory agents to treat inflammatory diseases in several models [ 1 , 2 , 6 , 29 ]. In 2020, one of these studies investigated whether Ok-PDRN exhibited anti-inflammatory activity using Sprague Dawley (SD) rats with ischemic colitis, which was induced via selective devascularization of the descending colon [ 29 ].…”

“…Ok-PDRN injection enhanced expression of A 2A R, VEGF, and caspase-3, as well as of ERK phosphorylation, but reduced the expression ratio of Bax/Bcl-2 and expression of inflammatory proteins, including COX-2, IL-1β, IL-6, and TNF-α. In 2016, two studies confirmed the anti-inflammatory effect of Om-PDRN in combination with hyaluronic acid (HA) using SD rats with induced colitis (i.e., an inflammatory bowel disease of the gastrointestinal tract) [ 1 , 2 ]. Intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS, 25 mg) and oral administration of dextran sulfate sodium (DSS, 8%) successfully induced experimental colitis in SD rats.…”

“…Further, colitis induced lipid peroxidation, neutrophil infiltration, and expression of pro-inflammatory cytokines (IL-1β and TNF-α) decreased in both models [ 1 ]. However, Om-PDRN treatment exhibited an inhibitory effect on colitis-induced changes [ 2 ]. Another study assessed whether Om-PDRN had anti-apoptotic and anti-inflammatory activities on SD rats with LPS-induced lung injuries [ 6 ].…”

“…Polydeoxyribonucleotide (PDRN), an active mixture of polynucleotides with a molecular weight ranging from 50 to 1500 kDa, is mainly extracted and purified from the sperm cells of Salmon trout (Oncorhynchus mykiss ) or Chum Salmon (Oncorhynchus keta ). Importantly, PDRN exhibits a high DNA percentage without active proteins or peptides [ 1 , 2 ]. This compound is currently used as a type of DNA-derived commercial drug, which has been approved by the Korea Food and Drug Administration and is often implemented in tissue repair and wound treatment [ 3 ].…”