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Abstract The thyroid glands are very sensitive to the action of chemical disruptors like Bisphenol A (BPA) which is a chemical pollutant widespread in the environment. Because of the few available data on the relation between BPA exposure and thyroid function, we intended to investigate the possible mechanism of BPA thyroid gland toxicity and its modulation by Ginger extract (GE) and pomegranate peel extract (PPE). BPA administration caused a significant increase of TSH, decrease T3 and T4 levels and a significant reduction of mRNA expression of thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase enzyme (TPO) and sodium iodide symporter (NIS). BPA decreased GSH concentration, SOD activity, increased MPO activity and MDA. Nrf-2 mRNA expression was significantly decreased with a reduction of hemoxygenase 1 (HO-1), an increase of iNOS mRNA expression and DNA fragmentation % in thyroid tissue exposed to BPA. These findings were confirmed by the histopathological features that showed severe damage of thyroid follicles and leukocytes infiltration in BPA treated rats. These biochemical and histological alterations were alleviated with ginger and pomegranate peel extracts administration plus BPA. In conclusion, our data showed that ginger extract is a potent antioxidant that can effectively protect against BPA induced thyroid oxidative damage by regulating the Nrf-2/HO-1 gene expression and enhancing thyroid hormones synthesis. Additionally, pomegranate peel extract is a potent antioxidant by up-regulating HO-1, TSHR gene expressions and decreasing the levels of MPO, MDA, iNOS and DNA damage, as well as by increasing GSH, SOD and thyroid hormones. Keywords: Thyrotoxicity, BPA, ginger, pomegranate, Nrf-2/HO-I, TSHR. |