title: 5-Aminoisoquinolin-1(2H)-one, a water-soluble poly (ADP-ribose) polymerase (PARP) inhibitor reduces the evolution of experimental periodontitis in rats.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Carmelo
authors.initials: C
authors.lastname: Muià
authors.forename: Dino
authors.initials: D
authors.lastname: Terrana
authors.forename: Salvatore
authors.initials: S
authors.lastname: Greco
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Domenico
authors.initials: D
authors.lastname: Santori
authors.forename: Giacomo
authors.initials: G
authors.lastname: Oteri
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cordasco
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: 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
chemical_list: C411425:5-aminoisoquinolinone; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases