Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines

David W. Paquette, Adam Rosenberg, Zsolt Lohinai, Gary J. Southan, Ray C. Williams, Steven Offenbacher, Csaba Szabo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs. Methods: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3% MEG, 0.3% GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests. Results: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing (%BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P <0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P <0.05). Although placebo-treated beagles demonstrated %BOP scores of 43% at week 8, GED- and MEG-treated beagles exhibited %BOP scores of 21% and 26%, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels. Conclusion: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalJournal of Periodontology
Volume77
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Gingivitis
Dogs
Placebos
Periodontal Index
Gels
Nitric Oxide Synthase Type II
Hemorrhage
Nitric Oxide
Nitrogen Compounds
Toothbrushing
Maximum Tolerated Dose
Bicuspid
Periodontal Diseases
2-mercaptoethylguanidine
bis(2-guanidinoethyl)disulfide
Ulcerative Colitis
Nitric Oxide Synthase
Arthritis
Free Radicals
Shock

Keywords

  • Dogs
  • Gingivitis
  • Inducible nitric oxide synthase
  • Periodontal disease
  • Reactive nitrogen species

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Paquette, D. W., Rosenberg, A., Lohinai, Z., Southan, G. J., Williams, R. C., Offenbacher, S., & Szabo, C. (2006). Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines. Journal of Periodontology, 77(3), 385-391. https://doi.org/10.1902/jop.2006.050049

Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines. / Paquette, David W.; Rosenberg, Adam; Lohinai, Zsolt; Southan, Gary J.; Williams, Ray C.; Offenbacher, Steven; Szabo, Csaba.

In: Journal of Periodontology, Vol. 77, No. 3, 03.2006, p. 385-391.

Research output: Contribution to journalArticle

Paquette, DW, Rosenberg, A, Lohinai, Z, Southan, GJ, Williams, RC, Offenbacher, S & Szabo, C 2006, 'Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines', Journal of Periodontology, vol. 77, no. 3, pp. 385-391. https://doi.org/10.1902/jop.2006.050049
Paquette DW, Rosenberg A, Lohinai Z, Southan GJ, Williams RC, Offenbacher S et al. Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines. Journal of Periodontology. 2006 Mar;77(3):385-391. https://doi.org/10.1902/jop.2006.050049
Paquette, David W. ; Rosenberg, Adam ; Lohinai, Zsolt ; Southan, Gary J. ; Williams, Ray C. ; Offenbacher, Steven ; Szabo, Csaba. / Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines. In: Journal of Periodontology. 2006 ; Vol. 77, No. 3. pp. 385-391.
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abstract = "Background: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs. Methods: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3{\%} MEG, 0.3{\%} GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests. Results: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing ({\%}BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P <0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P <0.05). Although placebo-treated beagles demonstrated {\%}BOP scores of 43{\%} at week 8, GED- and MEG-treated beagles exhibited {\%}BOP scores of 21{\%} and 26{\%}, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels. Conclusion: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.",
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T1 - Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines

AU - Paquette, David W.

AU - Rosenberg, Adam

AU - Lohinai, Zsolt

AU - Southan, Gary J.

AU - Williams, Ray C.

AU - Offenbacher, Steven

AU - Szabo, Csaba

PY - 2006/3

Y1 - 2006/3

N2 - Background: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs. Methods: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3% MEG, 0.3% GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests. Results: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing (%BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P <0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P <0.05). Although placebo-treated beagles demonstrated %BOP scores of 43% at week 8, GED- and MEG-treated beagles exhibited %BOP scores of 21% and 26%, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels. Conclusion: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.

AB - Background: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs. Methods: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3% MEG, 0.3% GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests. Results: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing (%BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P <0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P <0.05). Although placebo-treated beagles demonstrated %BOP scores of 43% at week 8, GED- and MEG-treated beagles exhibited %BOP scores of 21% and 26%, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels. Conclusion: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.

KW - Dogs

KW - Gingivitis

KW - Inducible nitric oxide synthase

KW - Periodontal disease

KW - Reactive nitrogen species

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