2245 Histopathological Evidence for Prevention of Porphyromonas gingivalis-induced Periodontitis by Topical Lipoxin Application in Rabbits
A. JAIN1, B. BEHBEHANI1, A. KANTARCI1, H. HASTURK1, N. PETASIS2, G.L. STAHL3, C.N. SERHAN3, and T.E. VAN DYKE1, 1 Boston University, MA, USA, 2 University of Southern California, Los Angeles, USA, 3 Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA

Lipoxins (LX) are antiinflammatory eicosanoid products of the lipoxygenase: lipoxygenase pathway. Synthetic stable lipoxin analogs represent a class of novel lipid mediators shown to prevent neutrophil-mediated tissue injury. Previously, we have found that experimental periodontal disease in rabbits can be interupted by local application of LXA4. OBJECTIVE: To analyze the histopathological changes associated with experimental periodontitis in rabbits in response to topically applied LXA4. METHODS: Experimental periodontitis was induced with silk sutures tied around mandibular second premolars bilaterally, followed by topical application of 108-109 CFU of P. gingivalis. In the experimental group (n=6), LXA4 was applied at a dose of 3mg per tooth, three times per week; control group (n=6) received vehicle alone. A third group of animals that did not receive any ligature or P. gingivalis challenge served as controls for the comparison of soft and hard tissue changes. After 6 weeks, rabbits were euthanized and mandibular block sections were obtained. Blocks were decalcified and embedded in parafin. Sections were stained with hematoxylin-eosin and Masson's Trichrome. Histological evaluation of samples, characterization of cellular inflammatory infiltrate and quantitative histomorphometric measurements were made. RESULTS: Severe alveolar bone loss (up to 60%) was observed at 6 weeks of experimental periodontitis. Increased multinucleated osteoclastic cells and inflammatory infiltrate dominated the pathology. While vehicle application did not result in any resolution of inflammation, LXA4 led to significant inhibition of bone loss (p<0.05). Histometry demonstrated a significant decrease in the inflammatory cell influx in the connective tissue at the LXA4 treated sites compared to controls (p<0.05). CONCLUSION: Topical application of a LXA4 analog was effective in preventing histological evidence of bone loss, inflammatory cell infiltration and connective tissue destruction in the rabbit periodontitis model. Endogenous inflammation resolving molecules may be a potential candidate for pharmacologic agents to prevent periodontitis. Supported by USPHS Grants 13499.

Seq #227 - Biologic Response Modifiers and Tissue Formation
3:45 PM-5:00 PM, Friday, 27 June 2003 Svenska Massan Exhibition Hall B

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