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

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.