Abstract

We investigated the role of PARP, a multifunctional nuclear enzyme in a ligature induced periodontitis model in rat. We also compared the outcome of ligature induced periodontitis in PARP1- deficient mice versus wild type mice. Rats were treated with phenanthridinone derivative PARP inhibitor PJ34 (Nature Med 7: 108-113, 2001) at a dose of 5 mg/kg i.p, 2 times per day for 7 days. On Day 8, gingivomucosal tissues encircling the mandibular 1st molars were removed on both sides and processed for poly(ADP-ribose) immunohistochemistry (indicator of PARP activation), plasma extravasation measurement by Evans blue technique, and alveolar bone loss measurement by videomicroscopy. In rats immunohistochemical analysis revealed significantly increased poly(ADP-ribose) nuclear staining (indicative of PARP activation) in the subepithelial connective tissue of the ligated side compared to the contralateral (control) side. PARP activation was absent in PARP-1 deficient mice and in rats treated with PJ34. Ligation significantly increased Evans blue extravasation in the gingivomucosal tissue and alveolar bone destruction compared to the control side. PARP inhibition, as well as PARP deficiency significantly reduced the plasma extravasation and the alveolar bone resorption of the ligated side compared to control. Thus, PARP activation plays a role in the pathogenesis of periodontal disease. References: 1.Lohinai Z, Benedek P, Fehér E et al: Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase in ligature-induced periodontitis in the rat. Br J Pharmacol, 1998; 123: 353-360 2.Lohinai Z, Stachlewitz RF, Virág L et al: Evidence for reactive nitrogen species formation in gingivomucosal tissues. J Dental Res, 2001; 80: 470-475 3.Virág L, Szabó C: The therapeutic potential of PARP inhibition. Pharmacological Reviews, 2002; 54: 375-429

Keywords: Ligation, gingivitis, periodontitis, oral flora, Bacteria, peroxynitrite, Nitric Oxide