Cadmium exposure is associated with ferroptosis-related redox/iron imbalance and altered abundance of selected m5C regulatory proteins in NIT-1 cells and mouse pancreatic tissue: A preliminary descriptive study.

Cadmium (Cd) is an environmental toxicant associated with pancreatic dysfunction and disordered glucose metabolism. Although ferroptosis has been implicated in Cd toxicity, whether Cd exposure is accompanied by changes in selected RNA 5-methylcytosine (m5C) regulatory proteins in pancreatic β-cell-related systems remains unclear. Here, mouse NIT-1 cells were exposed to CdSO4 (4 μmol/L), and ferroptosis-related injury was evaluated using ferrostatin-1 (Fer-1) and erastin together with assays of cell viability, LDH release, reactive oxygen species (ROS), malondialdehyde (MDA), intracellular Fe2+, and ferroptosis-related proteins. Mouse pancreatic tissue was analyzed after chronic CdSO4 exposure. CdSO4 reduced NIT-1 cell viability and increased LDH activity, ROS, MDA, and Fe2+ levels. Fer-1 partially improved cell viability and attenuated ROS and MDA, whereas erastin exacerbated Cd-associated injury. Cd exposure increased FTL abundance and decreased SLC7A11 and GPX4 in NIT-1 cells; chronic CdSO4 exposure in mice was accompanied by altered ferroptosis-related proteins, increased pancreatic Fe2+, and reduced serum insulin. In addition, Cd exposure was associated with altered abundance of selected m5C regulatory proteins, including decreased NSUN2 and increased TET2 in NIT-1 cells, and altered NSUN2, NSUN6, ALYREF, and TET2 in mouse pancreatic tissue. Overall, this preliminary descriptive study indicates that CdSO4 exposure is associated with ferroptosis-related redox/iron imbalance in NIT-1 cells and mouse pancreatic tissue, accompanied by altered abundance of selected m5C regulatory proteins. However, because serum and pancreatic Cd burdens, formal replicate-level correlation analyses, global or transcript-specific m5C marks, and causal regulatory experiments were not assessed, these findings should be interpreted as associative and descriptive evidence rather than as proof of an internal Cd burden-response relationship or a direct m5C-mediated mechanism of ferroptosis regulation.