AN0128 is a boron-containing compound with antibacterial and anti-inflammatory properties. To test its potential effectiveness in treating periodontal disease, we induced experimental periodontitis in the rat by placing ligatures and assessed the impact of AN0128 and positive and negative controls by micro-CT and histologic measurements. The formation of an inflammatory infiltrate was measured in hematoxylin-and-eosin-stained sections. Daily application of AN0128 (1%) compared with controls reduced bone loss by 38 to 44% (P < 0.05), while vehicle alone had no effect (P > 0.05). The reduction in bone loss with AN0128 was similar to that achieved with a NSAID, ketorolac, and Total toothpaste containing triclosan. AN0128 also reduced the level of gingival inflammation 42% compared with the ligature only (P < 0.05), whereas vehicle alone had no effect (P > 0.05). The results indicate that AN0128 significantly reduces the formation of an inflammatory infiltrate and reduces bone loss, measured histologically and by micro-CT.
Get full access to this article
View all access options for this article.
References
1.
Assuma R, Oates T, Cochran D, Amar S, Graves D -1998-. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol160:403–409.
2.
Baker SJ, Akama T, Zhang YK, Sauro V, Pandit C, Singh R, et al. -2006-. Identification of a novel boron-containing antibacterial agent -AN0128- with anti-inflammatory activity, for the potential treatment of cutaneous diseases. Bioorg Med Chem Lett16:5963–5967.
3.
Benkovic SJ, Baker SJ, Alley MR, Woo YH, Zhang YK, Akama T, et al. -2005-. Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH. J Med Chem48:7468–7476.
4.
Borrell LN, Burt BA, Taylor GW -2005-. Prevalence and trends in periodontitis in the USA: the NHANES, 1988 to 2000. J Dent Res84:924–930; published erratum in J Dent Res 85:287, 2006.
5.
Delima A, Karatzas S, Amar S, Graves DT -2002-. Inflammation and tissue loss caused by periodontal pathogens is reduced by IL-1 antagonists. J Infect Dis186:511–516.
6.
Graves DT, Cochran D -2003-. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol74:391–401.
7.
Haffajee AD, Socransky SS -2006-. Introduction to microbial aspects of periodontal biofilm communities, development and treatment. Periodontol 200042:7–12.
8.
Haffajee AD, Teles RP, Socransky SS -2006-. The effect of periodontal therapy on the composition of the subgingival microbiota. Periodontol 200042:219–258.
9.
Holt S, Ebersole J, Felton J, Brunsvold M, Kornman KS -1988-. Implantation of Bacteroides gingivalis in non-human primates initiates progression of periodontitis. Science239:55–57.
10.
Jeffcoat MK, Reddy MS, Haigh S, Buchanan W, Doyle MJ, Meredith MP, et al. -1995-. A comparison of topical ketorolac, systemic flurbiprofen, and placebo for the inhibition of bone loss in adult periodontitis. J Periodontol66:329–338.
11.
Kenworthy R, Baverel M -1981-. Studies of a periodontal tissue lesion in the rat, untreated or treated with chlorhexidine digluconate. J Clin Periodontol8:349–358.
12.
Kornman KS -1999-. Host modulation as a therapeutic strategy in the treatment of periodontal disease. Clin Infect Dis28:520–526.
13.
Leonard EP, Mandel EJ -1979-. Use of chlorhexidine gluconate to prevent bone resorption in the rice rat -annotation-. J Dent Res58:672.
14.
Listgarten MA, Loomer PM -2003-. Microbial identification in the management of periodontal diseases. A systematic review. Ann Periodontol8:182–192.
15.
Liu R, Bal HS, Desta T, Krothapalli N, Alyassi M, Luan Q, et al. -2006-. Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation. J Dent Res85:510–514.
16.
Lohinai Z, Benedek P, Feher E, Gyorfi A, Rosivall L, Fazekas A, et al. -1998-. Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol123:353–360; published erratum in Br J Pharmacol 123:741, 1998.
17.
Rosan B, Lamont R -2000-. Dental plaque formation. Microbes Infect2:1599–1607.
18.
Rosling B, Wannfors B, Volpe AR, Furuichi Y, Ramberg P, Lindhe J -1997-. The use of a triclosan/copolymer dentifrice may retard the progression of periodontitis. J Clin Periodontol24:873–880.
19.
Rovin S, Costich ER, Gordon HA -1966-. The influence of bacteria and irritation in the initiation of periodontal disease in germfree and conventional rats. J Periodontal Res1:193–204.
20.
Samejima Y, Ebisu S, Okada H -1990-. Effect of infection with Eikenella corrodens on the progression of ligature-induced periodontitis in rats. J Periodontal Res25:308–315.
21.
Sanavi F, Listgarten MA, Boyd F, Sallay K, Nowotny A -1985-. The colonization and establishment of invading bacteria in periodontium of ligature-treated immunosuppressed rats. J Periodontol56:273–280.
22.
Teng YT -2003-. The role of acquired immunity and periodontal disease progression. Crit Rev Oral Biol Med14:237–252.
23.
Teng YT, Nguyen H, Gao X, Kong YT, Gorczynski RM, Singh B, et al. -2000-. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest106:R59–R67.
24.
Weiner GS, DeMarco TJ, Bissada NF -1979-. Long term effect of systemic tetracycline administration on the severity of induced periodontitis in the rat. J Periodontol50:619–623.
25.
Wilensky A, Gabet Y, Yumoto H, Houri-Haddad Y, Shapira L -2005-. Three-dimensional quantification of alveolar bone loss in Porphyromonas gingivalis-infected mice using micro-computed tomography. J Periodontol76:1282–1286.
26.
Williams RC, Jeffcoat MK, Kaplan ML, Goldhaber P, Johnson HG, Wechter WJ -1985-. Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles. Science227:640–642.
