Toxicity of tetrabromobisphenol A to human thyroid follicular epithelial cells through oxidative stress: A combined analysis at the cellular and molecular levels

Tetrabromobisphenol A (TBBPA), a prominent brominated flame retardant (BFR), is a toxic pollutant. In view of the structural similarity of TBBPA to thyroid hormones, we investigated the toxic effects of TBBPA on human thyroid follicular epithelial cells (Nthy-ori3-1) at concentrations ranging from 0.02 to 100 μM. The findings of this study demonstrated that a 24-hour exposure to 10 μM TBBPA resulted a reduction of cell viability to 50.9 %. Concurrently, intracellular reactive oxygen species (ROS) levels were significantly elevated, and oxidative stress-related proteins, particularly those involved in the NRF2/KEAP1 pathway, were upregulated in the cells. It is noteworthy that, while catalase (CAT) activity increased, T-SOD enzyme activity was inhibited. To better understand the mechanism underlying the interaction between TBBPA and antioxidant enzymes, multispectral methods and molecular docking techniques were employed. These analyses revealed that TBBPA binds to antioxidant enzymes and induces structural changes that may impair their function. Altered enzyme activity may lead to abnormal ROS accumulation and contribute to apoptosis. Furthermore, the interactions between TBBPA and Cu/Zn-SOD and CAT have been demonstrated to exacerbate this process. This study provides valuable insights into the molecular mechanisms underlying TBBPA-induced thyroid cell toxicity.