Paquette David W, Rosenberg Adam, Lohinai Zsolt, Southan Garry J, Williams Ray C, Offenbacher Steven, Szabó Csaba
Department of Periodontology, School of Dentistry, Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, NC, USA.
J Periodontol. 2006 Mar;77(3):385-91. doi: 10.1902/jop.2006.050049.
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.
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.
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.
The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.
一氧化氮是由一氧化氮合酶的组成型和诱导型在宿主组织中产生的自由基。一氧化氮发挥生理作用，但也参与包括关节炎、溃疡性结肠炎和循环性休克在内的多种炎症性疾病的病理生理过程。在患有牙周病的人类和动物中也已证实诱导型一氧化氮合酶（iNOS）和活性氮产物的局部增加。这项双盲、随机、安慰剂对照的临床前研究考察了两种巯基烷基胍，即巯基乙胍（MEG）和胍基乙基二硫化物（GED），它们是iNOS抑制剂和活性氮清除化合物，对比格犬实验性牙龈炎发展的影响。
15只1岁雌性比格犬首先完成了一项为期2周的剂量递增实验，在此期间确定了MEG和GED凝胶的最大耐受剂量。此后，通过机械洁治使所有动物的牙龈达到最佳健康状态，随后在为期4周的洗脱期内进行严格的每日刷牙。然后通过停止菌斑控制并在8周内采用软食诱导实验性牙龈炎。比格犬随机接受0.3%MEG、0.3%GED或安慰剂（赋形剂）凝胶，每天两次局部应用于前磨牙。在基线以及第2、3、4、6和8周对牙龈炎症、出血倾向和龈上菌斑进行临床测量。使用Kruskal-Wallis检验对组间以及组对之间（活性药物与安慰剂）进行比较。
从基线到第7天，所有组的指标相似。此后，在接受安慰剂治疗的比格犬中观察到菌斑指数（PI）、牙龈指数（GI）和探诊出血百分比（%BOP）显著且随时间增加。用GED或MEG凝胶治疗的比格犬的平均GI评分在整个治疗期间保持在或低于基线水平。在第2、3、4和8周，MEG和GED组的GI评分显著低于安慰剂组（P<0.05）。此外，MEG和GED凝胶在8周时显著降低了牙龈出血反应（P<0.05）。尽管接受安慰剂治疗的比格犬在第8周时%BOP评分为43%，但接受GED和MEG治疗的比格犬的%BOP评分分别为21%和26%。由于在任何时间点PI评分均未发现统计学差异，两种巯基烷基胍似乎均未影响龈上菌斑水平。
这项临床前研究的数据表明，局部应用巯基烷基胍可能显著减轻比格犬的实验性牙龈炎。
