Heavy metal (HM) pollution, specifically cadmium (Cd) contamination, is a worldwide concern for its consequences for plant health and ecosystem stability. This review sheds light on the intricate mechanisms underlying Cd toxicity in plants and the various strategies employed by these organisms to mitigate its adverse effects. From molecular responses to physiological adaptations, plants have evolved sophisticated defense mechanisms to counteract Cd stress. We highlighted the role of phytochelatins (PC_n) in plant detoxification, which chelate and sequester Cd ions to prevent their accumulation and minimize toxicity. Additionally, we explored the involvement of glutathione (GSH) in mitigating oxidative damage caused by Cd exposure and discussed the regulatory mechanisms governing GSH biosynthesis. We highlighted the role of transporter proteins, such as ATP-binding cassette transporters (ABCs) and heavy metal ATPases (HMAs), in mediating the uptake, sequestration, and detoxification of Cd in plants. Overall, this work offered valuable insights into the physiological, molecular, and biochemical mechanisms underlying plant responses to Cd stress, providing a basis for strategies to alleviate the unfavorable effects of HM pollution on plant health and ecosystem resilience.

Per- and polyfluoroalkyl substances (PFASs) are a persistent bioaccumulating pollutants. Several environmental contaminants were shown to impair Sodium Iodide Symporter (NIS) function, thereby reducing iodide availability for Thyroid hormone (TH) synthesis. TH action critically depends on their transport across cell membranes. In particular, Monocarboxylate transporter 8 (MCT8) is one of the transporters of TH on cell membranes. This study aimed to evaluate the in vitro effects of PFHxA or PFOA on iodide uptake and MCT8-mediated TH transport. CHO-hNIS and MDCK-MCT8 were exposed to increasing concentrations of PFOA or PFHxA [0-0.01-0.1-1-10-100-1000 μM]. Cellular viability was assessed by trypan blue and WST-1. Iodide and T3 uptake were assessed by Sandell-Kolthoff (SK) reaction and confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Exposure to PFOA or PFHxA did not affect cell viability at any of the concentrations tested. In CHO-hNIS cells the exposure to PFHxA showed a significant non-monotonic reduction of iodide uptake. PFOA exposure also exhibited a non-monotonic pattern in reducing iodine uptake, although there were some differences compared to PFHxA. Moving to the evaluation of T3 uptake by MDCK-MCT8 cells exposed to PFAS, the results demonstrated that PFHxA inhibited T3 uptake in a non-monotonic pattern, whereas PFOA exposure also inhibited T3 uptake but did not exhibit a non-monotonic pattern. These findings reveal a non-monotonic concentration-response pattern for PFHxA but not PFOA in MDCK-MCT8 cells. The present study showed that the exposure to PFHxA or PFOA inhibited iodine and T3 uptake, often with a similar non-monotonic pattern. The potential clinical relevance of these findings stems from the central role of iodide uptake and thyroid hormone transport in maintaining thyroid hormone homeostasis.