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Dose–response effect of Montelukast on post-extraction dental socket repair and skeletal phenotype of mice

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Abstract

Bone metabolism and repair are directly regulated by arachidonic acid metabolites. At present, we analyzed the dose–response effects of a selective cysteinyl leukotriene receptor type-1 antagonist during bone repair after tooth extraction and on non-injured skeleton. Sixty-three 129 Sv/Ev male mice composed the groups: C—Control (saline solution); MTK2—2 mg/Kg of Montelukast (MTK) and MTK4–4 mg/Kg of MTK, daily administered by mouth throughout all experimental periods set at 7, 14, and 21 days post-operative. Dental sockets were analyzed by computed microtomography (microCT), histopathology, and immunohistochemistry. Femurs, L5 vertebra and organs were also removed for observation. Blood was collected for plasma bone and liver markers. Histopathology and microCT analysis revealed early socket repair of MTK2 and MTK4 animals, with significant increased BV/TV at days 14 and 21 compared to C. Higher plasma calcium was detected at days 7 and 21 in MTK4 in comparison to C, while phosphate was significantly increased in MTK2 in the same periods in comparison to C and MTK4. No significant differences were found regarding plasma ALP and TRAP, neither for local TRAP and Runx2 immunolabeling at the healing sockets. Organs did not present histological abnormalities. Increased AST levels have been detected in distinct groups and periods. In general, femur phenotype was improved in MTK treated animals. Collectively, MTK promoted early bone formation after tooth extraction and increased bone quality of femurs and vertebra in a time-dose-dependent manner, and should be considered as an alternative therapy when improved post-extraction socket repair or skeleton preservation is required.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

KHCR was supported by Fundação de Amparo à Pesquisa do Estado do Amazonas (Grant #42338.63998.1205.2019). MAM was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant #2019/16067-3).

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Authors and Affiliations

  1. Department of Oral Surgery and Dental Clinics, Araçatuba School of Dentistry, São Paulo State University—Unesp, Rua José Bonifácio 1192, Araçatuba, São Paulo, CEP 160188-05, Brazil

    Kim Henderson Carmo Ribeiro, Raquel Barroso Parra da Silva & Ana Carolina Zucon Bacelar

  2. Department of Basic Sciences, Araçatuba School of Dentistry, SãoPauloStateUniversity-Unesp, Rua José Bonifácio 1192, CEP 160188-05, Araçatuba, São Paulo, Brasil

    Ana Carolyna Becher Roseno, Ana Julia Moreno Barreto, Edilson Ervolino, Antonio Hernandes Chaves-Neto & Mariza Akemi Matsumoto

  3. Department of DentistryEndodontics and Dental MaterialsSchool of Dentistry, University of São Paulo, Alameda Otávio Pinheiro Brisola, 9-20, BauruBauru, São Paulo, CEP 7012-901, Brazil

    Marco Antônio Húngaro Duarte

  4. School of Dentistry, The University of Texas at Health Science Center at Houston (UTH), 1941 East Road, Houston, TX, 77054, USA

    Walid D. Fakhouri

  5. School of Podiatric Medicine, The University of Texas at Rio Grande Valley (UTRGV), 2120 Treasure Hills Blvd. Harlingen, Harlingen, TX, 78550, USA

    Cláudia Cristina Biguetti

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  1. Kim Henderson Carmo Ribeiro
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by KHCR, RB ParraS, ACBR, AJMB, ACZB, EE, MAHD, WDF, AHCN, CCB, MAM. The first draft of the manuscript was written by CCB and MAM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Ribeiro, K.H.C., da Silva, R.B.P., Roseno, A.C.B. et al. Dose–response effect of Montelukast on post-extraction dental socket repair and skeletal phenotype of mice. Odontology 111, 891–903 (2023). https://doi.org/10.1007/s10266-023-00800-5

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