PROTECTIVE EFFECTS OF MERCAPTOETHYLGUANIDINE, A SELECTIVE INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE, IN LIGATURE-INDUCED PERIODONTITIS IN THE RAT

1 Excessive production of nitric oxide (NO), and the generation of per oxynitrite have been implicated in various proinflammatory conditions. In the present study, using mercaptoethylguanidine (MEG), a selective inhibitor of iNOS and a peroxynitrite scavenger, we investigated the role of iNOS and peroxynitrite in a rat model of periodontitis. 2 Peri odontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left Ist molar. Animals were then divi ded into two groups: one group of rats was treated with MEG (30 mg kg( -1), i.p., 4 times per day for 8 days), animals in the other group rec eived vehicle. At day 8, the gingivomucosal tissue encircling the mand ibular Ist molars was removed on both sides from ligated and sham oper ated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti-iNOS serum. Plasma extravasatio n was measured with the Evans blue technique. Alveolar bone loss was m easured with a videomicroscopy. 3 Ligation caused a significant, more than 3 fold increase in the gingival iNOS activity, whereas it did not affect iNOS activity on the contralateral side, when compared to sham -operated animals. Immunohistochemical analysis revealed iNOS-positive macrophages, lymphocytes and PMNs in the connective tissue and immuno reactive basal layers of epithelium on side of the ligature, and only a few iNOS-negative connective tissue cells on the contralateral side. Ligation significantly increased Evans blue extravasation in gingivom ucosal tissue and alveolar bone destruction compared to the contralate ral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4 The present results demonstrated that ligatur e-induced periodontitis increases local NO production and that MEG tre atment protects against the associated extravasation and bone destruct ion. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role in the pathogenesis of p eriodontitis.