Inhibition of 5-lipoxygenase attenuates inflammation and BONE resorption in lipopolysaccharide-induced periodontal disease

• Published in: Journal of periodontology (1970)
• Main Authors: Lopes, Debora E M, Jabr, Camila L, Dejani, Naiara N, Saraiva, Amanda C, de Aquino, Sabrina G, Medeiros, Alexandra I, Rossa Junior, Carlos
• Format: Journal Article
• Language: English
• Published: United States 05-12-2017
• Subjects: Bone resorption; innate immunity; inflammation; periodontitis; leukotrienes
• ISSN: 1943-3670

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.
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.
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.
5-LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease.