DOI: 10.1111/jre.70158 ISSN: 0022-3484

Pharmacological Modulation of Nrf2 Signaling Regulates Oxidative Stress, Inflammation, and Alveolar Bone Loss in Experimental Periodontitis

Vitória Bonan Costa, Mariely Araújo de Godoi, Angelo Constantino Camilli, Isabela Rinaldi Gomes Nogueira, Veronica Canela Estevam dos Santos, Lucas Nogueira Ramos, Juliana Silva Siqueira, Camila Renata Corrêa Camacho, Morgana Rodrigues Guimarães Stabili

ABSTRACT

Aim

To investigate whether pharmacological modulation of Nrf2 signaling influences oxidative stress, inflammatory responses, and periodontal tissue destruction in experimental ligature‐induced periodontitis.

Methods

Ligature‐induced experimental periodontitis was established in rats treated with dimethyl fumarate (DMF), an Nrf2 activator, and/or ML385, a selective Nrf2 inhibitor. Alveolar bone loss, oxidative stress markers, inflammatory mediators, and histopathological changes were evaluated.

Results

Nrf2 activation attenuated alveolar bone loss, reduced oxidative stress, and decreased inflammatory mediators, accompanied by improved periodontal tissue organization. In contrast, Nrf2 inhibition exacerbated inflammation and increased periodontal tissue destruction.

Conclusion

Nrf2 signaling plays a regulatory role in periodontal inflammation and tissue breakdown. Pharmacological activation of Nrf2 exerts protective effects, whereas its inhibition aggravates disease severity.

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