Therapeutic actions of a mouthwash formulation of lipoxin A4 analog in experimental periodontitis

Date
2012
DOI
Authors
Yee, Cynthia
Version
OA Version
Citation
Abstract
Lipoxins are lipoxygenase-derived eicosanoids which display both anti-inflammatory and pro-resolving bioactions that include inhibition of neutrophil-mediated injury and stimulation of macrophage clearance of apoptotic neutrophils. Periodontal disease is a local inflammatory disease initiated by bacteria. However, the progression of disease depends on the host response to bacterial products, characterized by neutrophil-mediated tissue destruction. The purpose of this study is to investigate the therapeutic actions of a lipoxin analog, 9,12-LXA4, when used in a standard mouthwash in established periodontitis in rabbits. Experimental periodontitis was induced in 18 New Zealand white rabbits using ligatures followed by Porphyromonas gingivalis (10[9] colony forming units) topically applied to ligatured teeth for 6 weeks. Application of the lipoxin analog in an ethanol/sodium lauryl sulphate mouthwash/carrier for the treatment of periodontitis was evaluated in four groups of three animals formed based on different doses: 0.01[mu]M, 0.[mu]M, 1.0[mu]M, and 10[mu]M. In addition, a placebo group served as control while three animals received 2.8mM of the lipoxin analog suspended in ethanol as the reference group. Rabbits were sacrificed after 6 weeks of treatment. Mandibular block sections were decalcified and embedded in paraffin for histologic and histomorphometric analysis on hematoxylin and eosin-stained sections to evaluate the inflammatory cell infiltrate and to quantify bone levels. Macroscopic analysis was performed on methylene blue-stained hemiĀ­ mandibles for each rabbit to determine the hard tissue changes before and after treatments. In addition, samples of internal organs were obtained to perform histopathological evaluation for potential side-effects. 9,12-L mouthwash formulation resulted in the regeneration of hard and soft tissues which are lost to P. gingiva/is-induced periodontitis in rabbits. Both the infrabony defects and horizontal bone loss were restored. The sites treated with five different doses of 9,12-L showed statistically significant less crestal bone loss compared to placebo and baseline periodontitis with dose-dependent effect. The activity of 9,12-L was detected at all doses but significant differences between the placebo group started at the dose of 1.0 [mu]M and 10 [mu]M and was parallel with the reference formulation of 9,12-L in ethanol. Histologically, the 9,12-L -treated groups showed a reduction in inflammatory cell infiltrate as well as new bone and collagen formation. The findings of this study provide morphological and histological evidence that 9,12-L mouthwash formulation results in regeneration of pathologically lost tissues, including bone, and is a potential therapeutic approach in controlling the progression of chronic periodontal disease.
Description
Thesis/Dissertation (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2012 (Department of Oral Biology and Periodontology).
Includes bibliographic references: leaves 88-109.
License
This work is being made available in OpenBU by permission of its author, and is available for research purposes only. All rights are reserved to the author.