Combined Toxicity Assessment of Deoxynivalenol and Pb on HK-2 Cells Involved in Excessive ROS-Induced Ferroptosis.

The cocontamination of food by several mycotoxins and heavy metals poses significant health risks, and their combined toxic effects remain poorly understood. Particularly, specific studies exploring their combined impact on ferroptosis remain limited. In this work, we investigated the combined toxic effects of a mycotoxin, called deoxynivalenol (DON), and a heavy metal, called plumbum (Pb), and explored the potential mechanisms of DON and Pb co-occurrence via excessive ROS-induced ferroptosis in HK-2 cells. It was found that combined toxicity of DON and Pb showed a synergism at low concentrations and an antagonism at high concentrations. The increase of the ROS level and iron content as well as the change expression of four ferroptosis marker proteins were observed in DON and Pb individual and combined groups. Furthermore, the addition of ferroptosis inhibitor Fer-1 could mitigate the imbalance of oxidative stress and ferroptosis. Our results suggest that the co-occurrence of DON and Pb might pose a slight threat to the nephrotoxicity due to the interactions related to the excessive ROS-induced ferroptosis, which would provide valuable insights into their potential combined toxic impacts to human and animal health.