5-Aminoisoquinolin-1(2H)-one, a water-soluble poly (ADP-ribose) polymerase (PARP) inhibitor reduces the evolution of experimental periodontitis in rats

J Clin Periodontol. 2007 Feb;34(2):95-102. doi: 10.1111/j.1600-051X.2006.01016.x.

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.

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

Materials and 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.

Results and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillary Permeability / immunology
  • Capillary Permeability / physiology*
  • Edema / enzymology
  • Enzyme Inhibitors / pharmacology*
  • Gingiva / cytology
  • Gingiva / enzymology
  • Gingiva / immunology
  • Isoquinolines / pharmacology*
  • Male
  • Mouth Mucosa / cytology
  • Mouth Mucosa / enzymology
  • Mouth Mucosa / immunology
  • Neutrophil Infiltration / immunology
  • Periodontitis / enzymology*
  • Periodontitis / immunology
  • Periodontitis / prevention & control
  • Peroxidase / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric

Substances

  • 5-aminoisoquinolinone
  • Enzyme Inhibitors
  • Isoquinolines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Peroxidase
  • Poly(ADP-ribose) Polymerases