Modulation of TLR4, hBD-2, and hBD-3 expression and hepatic tissue response by systemic probiotics in experimental apical periodontitis in rats

Authors

  • Leopoldo Cosme-Silva lUniversidade Federal de Alagoas (UFAL), Faculdade de Odontologia
  • Renan Dal-Fabro University of Michigan School of Dentistry, Restorative Sciences and Endodontics, Department of Cariology,
  • Gabrielle Cabral Melville de Souza Tenório Universidade Federal de Alagoas (UFAL), Faculdade de Odontologia
  • José Alex da Silva schoolUniversidade Federal de Alagoas (UFAL), Faculdade de Odontologia
  • Edilson Ervolino Universidade Estadual Paulista (UNESP), Faculdade de Odontologia de Araçatuba, Departamento de Dentística, Endodontia
  • Letícia Cabrera Copalbo University of Detroit Mercy, School of Dentistry, Division of Clinical Essentials and Simulation
  • João Eduardo Gomes Filho lUniversidade Estadual Paulista (UNESP), Faculdade de Odontologia de Araçatuba, Departamento de Dentística, Endodontia

DOI:

https://doi.org/10.1590/

Keywords:

Apical periodontitis, Probiotics, Toll-like receptor, Beta-defensins, Liver

Abstract

Apical periodontitis is characterized by a robust inflammatory response and activation of innate immunity. Probiotics have been proposed as modulators of this response, but their local and systemic effects remain unclear. Objective  To evaluate whether systemic supplementation with L. rhamnosus LR-04 and L. acidophilus LA-14 modulates the expression of TLR4, hBD-2, and hBD-3 in a rat model of experimental apical periodontitis (AP), and to assess potential histopathological alterations in the liver. Methodology  Twenty-four male Wistar rats were randomly allocated into three groups (n=8): control (AP + water), AP + L. rhamnosus LR-04, and AP + L. acidophilus LA-14. AP was induced by exposing the pulp chambers of the first mandibular molars for 30 days. From the day of induction, probiotics (109 CFU/day via oral gavage) or water (control) were administered daily. After 30 days, the rats were euthanized. Mandibles were processed for immunohistochemical analysis of hBD-2, hBD-3, and TLR4 expression, which was assessed semi-quantitatively. Liver samples were collected, fixed, and stained with hematoxylin-eosin for histopathological evaluation of lobular inflammation, necrosis, portal inflammation, and fibrosis. Data were analyzed using the nonparametric Kruskal–Wallis test at a 5% significance level. Results  No hepatic histopathological alterations were observed in any group. Probiotic supplementation resulted in significantly greater hBD-2 immunoreactivity in periapical tissues compared to the control group (P<0.05). hBD-3 expression was significantly higher in the L. acidophilus LA-14 group than in both the control and L. rhamnosus LR-04 groups (P<0.05). TLR4 expression in periapical lesions was increased in both probiotic groups relative to control (P<0.05). Conclusion  Systemic supplementation with L. rhamnosus LR-04 and L. acidophilus LA-14 enhanced the local immune response in apical periodontitis, as evidenced by upregulation of TLR4, hBD-2, and hBD-3, without inducing detectable hepatic histopathological alterations.

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References

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Published

2026-05-22

Issue

Vol. 34 (2026)

Section

Original Articles

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How to Cite

Cosme-Silva, L., Dal-Fabro, R., Tenório, G. C. M. de S., Silva, J. A. da, Ervolino, E., Copalbo, L. C., & Gomes Filho, J. E. (2026). Modulation of TLR4, hBD-2, and hBD-3 expression and hepatic tissue response by systemic probiotics in experimental apical periodontitis in rats. Journal of Applied Oral Science, 34, e20250859. https://doi.org/10.1590/