5-Aminoisoquinolin-1(2H)-one, a water-soluble poly (ADP-ribose) polymerase (PARP) inhibitor reduces the evolution of experimental periodontitis in rats.
BACKGROUND
Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion and inflammation. Recent studies have demonstrated that PARP activation plays a crucial role in the pathogenesis of acute periodontal injury.


OBJECTIVE
We have investigated the effect of 5-aminoisoquinolin-1(2H)-one (5-AIQ), a water-soluble PARP inhibitor, in a rat model of periodontitis.


METHODS
Periodontitis was induced in rats by placing a 2/0 braided silk ligature around the lower left first molar. At day eight, the gingivomucosal tissue encircling the mandibular first molar was removed for biochemical and histological analysis.


CONCLUSIONS
Ligation significantly induced an increased neutrophil infiltration and a positive staining for PARP activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitonial injection of 5-aminoisoquinolin-1(2H)-one (5-AIQ) (5 mg/kg daily for eight days) significantly decreased all of the parameters of inflammation as described above. This suggests that inhibition of PARP may represent a novel approach for the treatment of periodontal disease.
Di Paola
Rosanna
R
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Messina, Italy.
Mazzon
Emanuela
E
Muià
Carmelo
C
Terrana
Dino
D
Greco
Salvatore
S
Britti
Domenico
D
Santori
Domenico
D
Oteri
Giacomo
G
Cordasco
Giancarlo
G
Cuzzocrea
Salvatore
S
D000818:Animals; D002199:Capillary Permeability / Q000276:immunology / Q000502:physiology*; D004487:Edema / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005881:Gingiva / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009061:Mouth Mucosa / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D010518:Periodontitis / Q000201:enzymology* / Q000276:immunology / Q000517:prevention & control; D009195:Peroxidase / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
C411425:5-aminoisoquinolinone; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases