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Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature‐induced periodontitis in the rat
Author(s) -
Lohinai Zsolt,
Benedek Péter,
Fehér Erzsébet,
Györfi Adrienn,
Rosivall László,
Fazekas Árpád,
Salzman Andrew L.,
Szabó Csaba
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701604
Subject(s) - extravasation , nitric oxide synthase , peroxynitrite , dental alveolus , connective tissue , nitric oxide , evans blue , chemistry , periodontitis , pathology , ligature , medicine , biochemistry , dentistry , enzyme , superoxide
Excessive production of nitric oxide (NO), and the generation of peroxynitrite 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. Periodontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left 1st molar. Animals were then divided 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 received vehicle. At day 8, the gingivomucosal tissue encircling the mandibular 1st molars was removed on both sides from ligated and sham operated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti‐iNOS serum. Plasma extravasation was measured with the Evans blue technique. Alveolar bone loss was measured with a videomicroscopy. 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 immunoreactive basal layers of epithelium on side of the ligature, and only a few iNOS‐reactive connective tissue cells on the contralateral side. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. The present results demonstrated that ligature‐induced periodontitis increases local NO production and that MEG treatment protects against the associated extravasation and bone destruction. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role in the pathogenesis of periodontitis.British Journal of Pharmacology (1998) 123 , 353–360; doi: 10.1038/sj.bjp.0701604