Objective: This study investigated whether polydeoxyribonucleotide (PDRN) may be efficacious in the treatment of peripheral artery occlusive diseases, which are a major cause of morbidity in Western countries and still lack standardized treatment. Methods: We investigated the effects of PDRN, a mixture of deoxyribonucleotides, in an experimental model of hind limb ischemia (HLI) in rats to stimulate vascular endothelial growth factor (VEGF)-A production and to avoid critical ischemia. The femoral artery was excised to induce HLI. Sham-operated on rats (sham HLI) were used as controls. Animals were treated daily with intraperitoneal PDRN (8 mg/kg) or its vehicle. Animals were euthanized at day 7, 14, and 21 after the evaluation of blood flow by laser Doppler. Dissected muscles were used to measure VEGF-A messenger RNA (mRNA) and protein expression, to evaluate edema, and to assess histologic damage. Results: Administration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 2.2 n-fold/-actin; HLI PDRN, 13.3 3.8 n-fold/-actin; P < .0001) and protein expression (HLI, 11 3.4 integrated intensity; HLI PDRN, 16 3.8 integrated intensity; P < .0001). The compound stimulated revascularization, as confirmed by blood flow restoration (P < .005 vs HLI vehicle), and blunted the histologic damage and the degree of edema. PDRN did not modify VEGF-A expression and blood flow in sham HLI animals. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.
Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model ofperipheral artery occlusive disease.
BITTO, ALESSANDRA;POLITO, FRANCESCA;ALTAVILLA, Domenica;MINUTOLI, Letteria;MIGLIORATO, Alba;SQUADRITO, Francesco
2008-01-01
Abstract
Objective: This study investigated whether polydeoxyribonucleotide (PDRN) may be efficacious in the treatment of peripheral artery occlusive diseases, which are a major cause of morbidity in Western countries and still lack standardized treatment. Methods: We investigated the effects of PDRN, a mixture of deoxyribonucleotides, in an experimental model of hind limb ischemia (HLI) in rats to stimulate vascular endothelial growth factor (VEGF)-A production and to avoid critical ischemia. The femoral artery was excised to induce HLI. Sham-operated on rats (sham HLI) were used as controls. Animals were treated daily with intraperitoneal PDRN (8 mg/kg) or its vehicle. Animals were euthanized at day 7, 14, and 21 after the evaluation of blood flow by laser Doppler. Dissected muscles were used to measure VEGF-A messenger RNA (mRNA) and protein expression, to evaluate edema, and to assess histologic damage. Results: Administration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 2.2 n-fold/-actin; HLI PDRN, 13.3 3.8 n-fold/-actin; P < .0001) and protein expression (HLI, 11 3.4 integrated intensity; HLI PDRN, 16 3.8 integrated intensity; P < .0001). The compound stimulated revascularization, as confirmed by blood flow restoration (P < .005 vs HLI vehicle), and blunted the histologic damage and the degree of edema. PDRN did not modify VEGF-A expression and blood flow in sham HLI animals. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.Pubblicazioni consigliate
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