Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat

Zsolt Lohinai, Péter Benedek, Erzsébet Fehér, Adrienn Györfi, László Rosivall, Árpád Fazekas, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

1. 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. 2. 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. 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 immunoreactive 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 gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. 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.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalBritish Journal of Pharmacology
Volume123
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Periodontitis
Nitric Oxide Synthase Type II
Ligation
Peroxynitrous Acid
Evans Blue
Nitric Oxide
Bone and Bones
Alveolar Bone Loss
Connective Tissue Cells
Video Microscopy
Silk
2-mercaptoethylguanidine
Cervix Uteri
Connective Tissue
Epithelium
Immunohistochemistry
Macrophages
Lymphocytes
Therapeutics
Serum

Keywords

  • Cytokine
  • Gingivitis
  • Inducible nitric oxide synthase
  • Ligature
  • Lipopolysaccharide
  • Nitric oxide
  • Periodontitis
  • Tissue destruction

ASJC Scopus subject areas

  • Pharmacology

Cite this

Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. / Lohinai, Zsolt; Benedek, Péter; Fehér, Erzsébet; Györfi, Adrienn; Rosivall, László; Fazekas, Árpád; Salzman, Andrew L.; Szabo, Csaba.

In: British Journal of Pharmacology, Vol. 123, No. 3, 1998, p. 353-360.

Research output: Contribution to journalArticle

Lohinai, Zsolt ; Benedek, Péter ; Fehér, Erzsébet ; Györfi, Adrienn ; Rosivall, László ; Fazekas, Árpád ; Salzman, Andrew L. ; Szabo, Csaba. / Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. In: British Journal of Pharmacology. 1998 ; Vol. 123, No. 3. pp. 353-360.
@article{04aea8b61d3e4c10a7a9837183ec3523,
title = "Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat",
abstract = "1. 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. 2. 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. 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 immunoreactive 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 gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. 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.",
keywords = "Cytokine, Gingivitis, Inducible nitric oxide synthase, Ligature, Lipopolysaccharide, Nitric oxide, Periodontitis, Tissue destruction",
author = "Zsolt Lohinai and P{\'e}ter Benedek and Erzs{\'e}bet Feh{\'e}r and Adrienn Gy{\"o}rfi and L{\'a}szl{\'o} Rosivall and {\'A}rp{\'a}d Fazekas and Salzman, {Andrew L.} and Csaba Szabo",
year = "1998",
doi = "10.1038/sj.bjp.0701604",
language = "English (US)",
volume = "123",
pages = "353--360",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat

AU - Lohinai, Zsolt

AU - Benedek, Péter

AU - Fehér, Erzsébet

AU - Györfi, Adrienn

AU - Rosivall, László

AU - Fazekas, Árpád

AU - Salzman, Andrew L.

AU - Szabo, Csaba

PY - 1998

Y1 - 1998

N2 - 1. 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. 2. 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. 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 immunoreactive 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 gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. 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.

AB - 1. 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. 2. 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. 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 immunoreactive 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 gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. 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.

KW - Cytokine

KW - Gingivitis

KW - Inducible nitric oxide synthase

KW - Ligature

KW - Lipopolysaccharide

KW - Nitric oxide

KW - Periodontitis

KW - Tissue destruction

UR - http://www.scopus.com/inward/record.url?scp=0031963653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031963653&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0701604

DO - 10.1038/sj.bjp.0701604

M3 - Article

VL - 123

SP - 353

EP - 360

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -