Systemic inhibition of 5-lipoxygenase by MK-886 exacerbates apical periodontitis bone loss in a mouse model

Author(s)

Petean, Igor Bassi Ferreira ; Silva-Sousa, Alice Correa ; da Silva, Raquel Assed Bezerra ; Lucisano, Marilia Pacifico ; da Silva, Lea Assed Bezerra ; de Castro, Guilherme Piedade Assed ; Sousa-Neto, Manoel Damiao ; Faccioli, Lucia Helena ; Paula-Silva, Francisco Wanderley Garcia

• Document type: Journal article
• Source: BMC ORAL HEALTH; v. 23, n. 1, p. 9-pg., 2023-01-10.

Abstract

Background To investigate if 5-LO selective inhibitor (MK-886) could be used for systemic treatment of experimentally induced apical periodontitis in a mouse model.MethodsTwenty-four C57BL/6 mice were used. After coronal opening, a solution containing Escherichiacoli LPS (1.0 mu g/mu L) was inoculated into the root canals of the lower and upper right first molars (n = 72 teeth). After 30 days apical periodontitis was established, and the animals were treated with MK-886 (5 mg/kg), a 5-LO inhibitor, for 7 and 14 days. The tissues were removed for histopathological and histometric analyses, evaluation of osteoclast number and gene expression for receptor activator of nuclear factor kappa-B (Tnfrsf11a), receptor activator of nuclear factor kappa-B ligand (Tnfsf11), osteoprotegerin (Tnfrsf11b), tartrate-resistant acid phosphatase (Acp5), matrix metalloproteinase-9 (Mmp9), cathepsin K (Ctsk) and calcitonin receptor (Calcr). Statistical data analysis was performed using Kruskal Wallis followed by Dunn's tests (alpha = 0.05).Results Administration of MK-886 for 7 days exerted no effect on apical periodontitis progression compared to LPS inoculation without treatment (p = 0.3549), while treatment for 14 days exacerbated bone loss (p < 0.0001). Administration of MK-886 enhanced osteoclastogenesis signaling and osteoclast formation within 7 days (p = 0.0005), but exerted no effect at 14 days (p > 0.9999). After 7 days of treatment, MK-886 induced mRNA expression for Acp5 (p = 0.0001), Calcr (p = 0.0003), Mmp9 (p = 0.0005) and Ctsk (p = 0.0008), however no effect in those gene expression was observed after 14 days (p > 0.05).Conclusion Systemic treatment with MK-886 exacerbated LPS-induced apical periodontitis in a mouse model. (AU)

• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/17611-4 - Mechanisms involved in the regulation of 5-lipoxygenase pathway in experimentally-induced apical periodontitis
• Grantee: Francisco Wanderley Garcia de Paula e Silva
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/09595-7 - The role of selective and non-selective inhibitors enzyme cyclooxygenase-2 and 5-lipoxygenase enzyme in osteoclastogenesis after the development of experimental periapical
• Grantee: IGOR BASSI FERREIRA PETEAN
• Support Opportunities: Scholarships in Brazil - Scientific Initiation