Ginger extract ameliorates bisphenol A (BPA)-induced disruption in thyroid hormones synthesis and metabolism: Involvement of Nrf-2/HO-1 pathway.

Environmental exposure to BPA is alarming because of the potential health threats for example those concerning the thyroid glands which may show signs of oxidative stress. This original study aimed to investigate the possible antioxidant protective effects of ginger extract (GE) against BPA-induced thyroid injury in male rats, focusing on its effect on Nrf-2/HO-1 signaling and thyroid hormone synthesis regulating genes. The cascade of events in thyroid injury induced by chronic exposure to BPA (200 mg/kg b.w/day for 35 days) involved a preliminary overproduction of ROS followed by significant (p ≤ 0.05) depletion of reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity as well as significant increases of malondialdehyde (MDA) contents, myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) gene expression. These actions consequently down-regulate the Nrf-2/HO-I signaling which eventually resulting in the DNA fragmentation within the thyroid tissues. Moreover, BPA administration caused a reduction of thyroid iodide uptake evidenced by significant inhibitions (p ≤ 0.05) of sodium-iodide symporter (NIS), thyroid peroxidase (TPO) and thyroid-stimulating hormone receptor (TSHR) mRNA expressions within the thyroid glands. A subsequent significant decreased serum levels of T3 and T4 accompanied by a significantly increased serum TSH level were also detected. These findings were confirmed by the severe pathological changes detected in the thyroid tissue of BPA treated rats. These biochemical and histological alterations were significantly alleviated with ginger administration (250 mg/kg b.w/day for 35 days) plus BPA. In conclusion, ginger extract is a potent antioxidant that can effectively protect against BPA-induced thyroid oxidative damage by activating the Nrf-2/HO-1 gene expressions and enhancing the thyroid hormones synthesis. This is the first study to show the contribution of Nrf-2/HO-1 pathway to the protective effect of ginger extract against BPA-induced thyroid oxidative damage and thyroid hormonal disruption.