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Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Pallio, Giovanni;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Bitto, Alessandra;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Pizzino, Gabriele;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Galfo, Federica;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Irrera, Natasha;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Squadrito, Francesco;
Affiliation
Department of Human Pathology, University of Messina Messina, Italy
Squadrito, Giovanni;
Affiliation
Section of Pharmacology, Department of Clinical and Experimental Medicine, Medical School, University of Messina Messina, Italy
Pallio, Socrate;
Affiliation
Department of Biomedical Sciences and Morphological and Functional Images, University of Messina Messina, Italy
Anastasi, Giuseppe P.;
Affiliation
Department of Human Pathology, University of Messina Messina, Italy
Cutroneo, Giuseppina;
Affiliation
Department of Human Pathology, University of Messina Messina, Italy
Macrì, Antonio;
Affiliation
Department of Biomedical Sciences and Morphological and Functional Images, University of Messina Messina, Italy
Altavilla, Domenica

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 A 2A 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 A 2A 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 A 2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

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License Holder: Copyright © 2016 Pallio, Bitto, Pizzino, Galfo, Irrera, Squadrito, Squadrito, Pallio, Anastasi, Cutroneo, Macrì and Altavilla.

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