Iron's silent betrayal: Ferritinophagy-driven mitochondrial damage mediates polylactic acid nanoplastics and Cr(VI)-induced cardiac injury

Nanoplastics (NPs) and chromium (Cr) are prevalent in environments, significantly polluting agricultural settings and food, thereby posing humans inevitably exposed to these toxic substances. As a biodegradable plastic, polylactic acid (PLA) is different from other petroleum-based nanoplastics and its toxicity remains unknown. This study investigated the toxicity of PLA NPs and Cr(VI), exploring the mechanisms underlying their synergistic cardiotoxicity. We indicated that co-exposure of mice to PLA NPs and Cr(VI) in drinking water for 30 days exhibited an intracellular redox imbalance, excessive production of mitochondrial reactive oxygen species (mtROS), iron overload, and the onset of ferritinophagy. By inhibiting ferroptosis and facilitating the clearance of mtROS, we observed a significant alleviation of cardiac injury. In summary, our study investigated the synergistic cardiotoxicity of PLA NPs and Cr(VI), aiming to provide new insights and references for the risk assessment of NPs and heavy metals.