Ferroptosis Induced by Micro/Nanoplastics: Mechanisms, Toxic Effects, and Implications for Aquaculture

Abstract

In aquaculture ecosystems, the accumulation of microplastics and nanoplastics (MNPs) poses an increasing threat to the health, disease resistance, and productivity of farmed species. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, offers a new perspective for elucidating the toxicity mechanisms of MNPs. Understanding this mechanism is particularly critical for assessing and mitigating the health risks of MNPs in aquaculture. This paper provides a critical review of recent progress on MNPs-induced ferroptosis. Mechanistically, MNPs trigger ferroptosis by inducing oxidative stress and lipid peroxidation, disrupting iron homeostasis, inhibiting the GPX4 antioxidant system, and regulating signaling pathways such as Nrf2 and p53/Fosl1. Nanoscale particles may act primarily via endocytosis and intracellular interactions to induce ferroptosis, whereas microscale particles exert effects mainly through surface interactions, mechanical stress, and metabolic disruption, yet the outcome is also modulated by polymer type, surface charge, shape, aging, and protein corona formation. At the organ level, MNPs-induced ferroptosis is associated with damage to the intestine, gonads, liver, cardiovascular system, nervous system, gills, and immune organs, and is amplified by co-exposure with heavy metals and organic pollutants. For aquaculture practice, molecular markers such as MDA, GSH, and GPX4 can serve as tiered early warning indicators, with intensive pond and cage culture systems facing the highest risk. Feasible interventions include dietary antioxidant supplementation, water treatment, feed quality control, and regular replacement of aged plastic infrastructure. This review provides a theoretical basis for assessing MNPs health risks and developing practical management strategies for sustainable aquaculture.