mpact of citrus flavonoid supplementation on inflammation in lipopolysaccharide-induced periodontal disease in mice

Authors: CARVALHO, JHONATHAN - Sao Paulo State University (UNESP); RAMADAN, DANIA - Sao Paulo State University (UNESP); GONÇALVES,VINICIUS - Sao Paulo State University (UNESP); BRUNETTI, IGUATEMY - Sao Paulo State University (UNESP); CESAR, THAIS B. - Sao Paulo State University (UNESP); Manthey, John; SPOLIDORIO, LUÍS C. - Sao Paulo State University (UNESP)

Submitted to: Food & Function
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/2021
Publication Date: 4/26/2021
Citation: Carvalho, Jhonathan, Ramadan, Dania, Gonçalves,Vinicius, Brunetti, Iguatemy, Cesar, Thais B., Manthey, J.A., Spolidorio, Luís C. 2021. Impact of citrus flavonoid supplementation on inflammation in lipopolysaccharide-induced periodontal disease in mice. Food & Function. https://doi.org/10.1039/D0FO03338C.
DOI: https://doi.org/10.1039/D0FO03338C

Interpretive Summary: Eriocitrin and eriodictyol are two compounds in limes and lemons with proven anti-oxidant properties in animals. The anti-oxidant effects of these compounds allow them to block inflammation in animals dosed with these compounds. The results of this study suggest that a diet supplemented with the citrus compounds eriocitrin or eriodictyol, and fed to rats, may aid in the prevention of periodontal disease, representing a potential method to enhance local immunity and host defense.

Technical Abstract: Background: In general, the consumption of flavonoid-rich foods may influence the control/dysregulation of the magnitude and duration of inflammation and oxidative stress, which are known to contribute to multiple pathologies. Information is scarce regarding the impact of diets supplemented with citrus flavonoids in periodontal disease. Herein, we investigated whether a diet supplemented with the pure citrus flavonoids eriocitrin or eriodictyol altered the course of the inflammatory response associated with LPS-induced periodontal disease in mice. Methods: Sixty BALB/c mice received a standard diet or a diet supplemented with different concentrations of eriocitrin or eriodictyol. After 30 days of food supplementation, a solution containing LPS from Escherichia coli was injected into the gingival tissues three times/week for 4 weeks. Neutrophils, mononuclear cells, and eosinophils were assessed using a severity analysis system in H&E-stained sections and modified picrosirius red. The activities of myeloperoxidase (MPO), a marker of granulocyte infiltration, and eosinophil peroxidase (EPO) were determined spectrophotometrically. Oxidative stress was evaluated by measuring lipoperoxidation (thiobarbituric acid reactive species — TBARS) and antioxidant enzyme activity (superoxide dismutase — SOD, catalase — CAT and glutathione peroxidase — GPx). Interleukin (IL)-1ß, TNF-a, and IL-10 were quantified by multiplex immunoassay. Results: Periodontal inflammation was significantly inhibited by citrus flavonoid food supplementation, including reduced flatness of the gingival epithelium, chronic and acute inflammatory cell infiltration, and loss of connective tissue in the gingival papillae. Both eriocitrin and eriodictyol inhibited gingival IL-1ß and TNF-a and increased IL-10 secondary to periodontitis. Significant protection and decreased MPO and EPO activity were detected in the periodontal tissue of citrus flavonoid-treated animals. In addition, SOD, CAT, and GPx activities were decreased, which was attributed to the control of inflammatory response and oxidative damage by flavonoids. Similarly, TBARS content was reduced compared to that of the LPS group, indicating decreased oxidative stress. Conclusions: These results suggest that a diet supplemented with the citrus flavonoids eriocitrin or eriodictyol may aid in the prevention of periodontitis, representing a potential method to enhance local immunity and host defense.