Inhibition of Experimental Gingivitis in Beagle Dogs With Topical Mercaptoalkylguanidines

• Autores: Steven Offenbacher, Csaba Szabó, David W. Paquette, Adam Rosenberg, Zsolt Lohinai, Garry J. Southan, Ray C. Williams
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 77, Nº. 3, 2006, págs. 385-391
• Idioma: inglés
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• Resumen

  • Inhibition of Experimental Gingivitis in Beagle Dogs With Topical Mercaptoalkylguanidines David W. Paquette,* Adam Rosenberg,* Zsolt Lohinai,† Garry J. Southan,‡ Ray C. Williams,* Steven Offenbacher,* and Csaba Szabó†‡ *Department of Periodontology, School of Dentistry, Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, NC.

    †Department of Human Physiology and Clinical Experimental Research, Semmelweis University Medical School, Budapest, Hungary.

    ‡Inotek Pharmaceuticals, Beverly, MA.

    Correspondence: Dr. David W. Paquette, Department of Periodontology, School of Dentistry, Comprehensive Center for Inflammatory Disorders, University of North Carolina, Brauer Hall, CB 7450, Chapel Hill, NC 27599-7450. E-mail: david_paquette@dentistry.unc.edu.

    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.

    KEYWORDS: Dogs, gingivitis, inducible nitric oxide synthase, periodontal disease, reactive nitrogen species Cited by David Polak, Conchita Martin, Ignacio Sanz-Sánchez, Nurit Beyth and Lior Shapira. (2014) Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review. Journal of Clinical Periodontology, n/a-n/a.

    Online publication date: 1-Dec-2014.

    CrossRef Lihui Weng, Christine Falabella and Weiliam Chen. 2013. Carbohydrate-Derived Self-Crosslinkable In Situ Gelable Hydrogels for Modulation of Wound Healing. Polymeric Biomaterials, 739-782.

    CrossRef Ana Nemec, Zlatko Pavlica, Milan Petelin, David A. Crossley, Marjeta Šentjurc, Aleš Jerin, Damijan Eržen, Irena Zdovc, Tina Hitti and Uroš Skalerič. (2010) Systemic use of selective iNOS inhibitor 1400W or non-selective NOS inhibitor l-NAME differently affects systemic nitric oxide formation after oral Porphyromonas gingivalis inoculation in mice. Archives of Oral Biology 55, 509-514.

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