Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.
Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Giovanni
G
Pallio
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Alessandra
A
Bitto
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Gabriele
G
Pizzino
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Federica
F
Galfo
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Natasha
N
Irrera
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Francesco
F
Squadrito
Department of Human Pathology, University of Messina Messina, Italy.
Giovanni
G
Squadrito
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Socrate
S
Pallio
Department of Biomedical Sciences and Morphological and Functional Images, University of Messina Messina, Italy.
Giuseppe P
GP
Anastasi
Department of Human Pathology, University of Messina Messina, Italy.
Giuseppina
G
Cutroneo
Department of Human Pathology, University of Messina Messina, Italy.
Antonio
A
Macrì
Department of Biomedical Sciences and Morphological and Functional Images, University of Messina Messina, Italy.
Domenica
D
Altavilla
A2A agonist; PDRN; apoptosis; colitis; inflammation