title: Inhibition of experimental gingivitis in beagle dogs with topical salivary histatins.
abstract: Histatins, histidine-rich proteins found within parotid and submandibular secretions, are a novel class of endogenous peptides with antimicrobial properties. This masked, randomized, placebo-controlled preclinical investigation examined the effect of 3 topical histatins on the development of plaque and gingivitis in beagle dogs. 16, female, 1-year-old beagles were brought to optimal gingival health by mechanical scaling and polishing followed by rigorous daily tooth brushing. At the conclusion of this pretreatment period, dogs were randomly divided into 4 groups for the application of test formulations, and were placed on a plaque-promoting diet. Test agents included 3 synthetic salivary histatins (histatin 5, P-113 and P-113D) which were incorporated in hydroxypropyl methylcellulose gel at a concentration of 0.125%, and a placebo, or negative control, which was the gel vehicle alone. Throughout the 10-week treatment period, test formulations (2.0 ml) were applied 2 x daily to all premolar teeth using a Monojet syringe. Plaque formation and gingival inflammation were assessed using the plaque (PI) and gingival (GI) indices on days 0, 7, 14, 21, 28, 42, 56 and 70. Furthermore, bleeding to probing was recorded as a percent of sites (%BOP) and according to the modified sulcus bleeding index (mSBI). Comparisons among groups and between group pairs (active versus placebo) were made with Kruskal-Wallis tests with the average of data over the interval, days 14-42, being the primary focus of the analysis. From baseline to day 7, all groups expressed similar indices. Thereafter, overall significant differences among the groups were noted at day 42 for PI, at days 21, 28, 42 and 70 for GI, and at days 14 and 28 for %BOP (p < 0.05). In particular, beagles treated with P-113 demonstrated significantly lower PI scores at day 42 (p < 0.05), significantly lower GI scores from days 21 through 42 (p < 0.05), and significantly lower %BOP scores at days 14 and 28 (p < 0.05) compared to beagles treated with placebo. Beagles treated with P-113D exhibited significantly lower GI at day 42 compared to the placebo (p < 0.05). For the primary analysis conducted over the midtreatment interval (days 14-42), significant differences were detected for all parameters except mSBI (p < 0.05). Accordingly, significantly lower PI scores were found for P-113, lower GI scores for P-113 and P-113D, and lower %BOP for P-113 and P-113D compared to placebo (p < 0.05). These data indicate that in the beagle model, salivary histatins, P-113 and P-113D, topically applied, can significantly reduce clinical signs of plaque formation and gingival inflammation.
authors.affiliation: Department of Periodontics, University of North Carolina School of Dentistry, Chapel Hill, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Paquette
authors.forename: G S
authors.initials: GS
authors.lastname: Waters
authors.forename: V L
authors.initials: VL
authors.lastname: Stefanidou
authors.forename: H P
authors.initials: HP
authors.lastname: Lawrence
authors.forename: P M
authors.initials: PM
authors.lastname: Friden
authors.forename: S M
authors.initials: SM
authors.lastname: O'Connor
authors.forename: J D
authors.initials: JD
authors.lastname: Sperati
authors.forename: F G
authors.initials: FG
authors.lastname: Oppenheim
authors.forename: L H
authors.initials: LH
authors.lastname: Hutchens
authors.forename: R C
authors.initials: RC
authors.lastname: Williams
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003773:Dental Plaque / Q000517:prevention & control*; D003774:Dental Plaque Index; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005891:Gingivitis / Q000517:prevention & control*; D010512:Periodontal Index; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D000099053:Histidine-Rich Glycoprotein
chemical_list: D011506:Proteins; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein