Therapeutic actions of a mouthwash formulation of lipoxin A4 analog in experimental periodontitis
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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.
Includes bibliographic references: leaves 88-109.
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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.