Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats

Abstract

Polyphenols are class of plant secondary metabolites that exert various beneficial effects. Namely, citrus polyphenols, naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving redox and metabolic status. However, polyphenols also interfere with thyroid peroxidase (TPO) activity and might affect thyroid structure and hormone production. Keeping in mind impaired thyroid function at older age, in this study we tested weather NAR or HES administration could induce structural and immunohistochemical changes in male 24-monthold Wistar rats. NAR or HES were administrated orally (15 mg/kg) during 4 weeks, while control groups received vehicle, sunflower oil. Stereological analyses (absolute and relative volume of epithelium, colloid and interstitium) and qualitative immunohistochemical examination of TPO and vascular endothelial growth factor (VEGF) proteins were performed. Results showed that thyroid structure of both flavanone-treated groups was characterized by lower (p < 0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p < 0.05) relative volume of interstitium in comparison with the controls. These changes were more prominent after NAR even no hypertrophy or absolute thyroid volume change was detected. TPO expression was localized in the cytoplasm and on the apical membrane of the active follicles, showing stronger immunostaining in both flavanone treated group in comparison with the controls. VEGF immunohistochemical expression was localized in the thyrocytes’s cytoplasm of thyrocytes and C cells, being stronger in flavanone-treated animals. In conclusion, both citrus flavanones induced structural alteration of thyroid tissue. Depleted colloid and stronger apical TPO immunostaining in the thyrocytes indicate higher thyroid hormone secretion and production. In line with this, interstitium volume increment, and higher VEGF expression in thyroid parenchyma might be due to a better blood supply and the expansion of microcirculation around active follicles in the thyroid of old-aged males.