Inhibition of 5‐lipoxygenase attenuates inflammation and bone resorption in lipopolysaccharide‐induced periodontal disease |
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Authors: | Debora E.M. Lopes Camila L. Jabr Naiara N. Dejani Amanda C. Saraiva Sabrina G. de Aquino Alexandra I. Medeiros Carlos Rossa Junior |
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Affiliation: | 1. Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University, Araraquara, Sao Paulo, Brazil;2. Department of Biological Sciences, School of Pharmaceutical SciencesSao Paulo State University;3. Health Sciences Center, School of Dentistry, Federal University of Paraiba, Joao Pessoa, Paraíba, Brazil |
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Abstract: | 1 Background Arachidonate‐5‐lipoxygenase (5‐LO) activity and increased leukotriene B4 (LTB4) production have been implicated in various inflammatory conditions. Increased production of leukotrienes has been associated with periodontal diseases; however, their relative contribution to tissue destruction is unknown. In this study, an orally active specific 5‐LO inhibitor is used to assess its role in inflammation and bone resorption in a murine model of lipopolysaccharide (LPS)‐induced periodontal disease. 2 Methods Periodontal disease was induced in Balb/c mice by direct injections of LPS into the palatal gingival tissues adjacent to the maxillary first molars three times per week for 4 weeks. Animals were treated with biochemical inhibitor (2 mg/kg/daily) or the same volume of the vehicle by oral gavage. Microcomputed tomography analysis was used to assess bone resorption. Enzyme immunoassay determined LTB4, and enzyme‐linked immunosorbent assays quantified tumor necrosis factor (TNF), interleukin (IL)‐12, and IL‐10 in gingival tissues. Histologic sections were used for the morphometric analysis (number of neutrophils and mononuclear cells). Osteoclasts were counted in tartrate‐resistant acid phosphatase–stained sections. 3 Results Administration of 5‐LO inhibitor effectively reduced production of LTB4 (23.7% decrease) and significantly reduced TNF and IL‐12 levels in gingival tissues. Moreover, reduction of LTB4 levels in gingival tissues was associated with a significant decrease in bone resorption and a marked reduction in number of osteoclasts and inflammatory cells. 4 Conclusion 5‐LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease. |
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Keywords: | Bone resorption inflammation innate immunity leukotrienes periodontitis |
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