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Synergistic kidney toxicity of polylactic acid nanoplastics and Cr(VI): Ferroptosis aggravated by mitophagy

Chemico-Biological Interactions 2026
Yuankun Zhou, Yuankun Zhou, Jiajun Guo, Jiajun Guo, Xiaoyan Feng, Xiaoyan Feng, Hengyi Xu, Hengyi Xu

Summary

Researchers investigated the combined kidney toxicity of polylactic acid nanoplastics and hexavalent chromium in mice. The study found that co-exposure produced synergistic kidney damage through ferroptosis aggravated by mitophagy, suggesting that even bioplastic-derived nanoplastics can enhance heavy metal toxicity when both contaminants are present together.

Polymers
Body Systems
Models

Nanoplastics (NPs) and chromium (Cr) are ubiquitous in the environment, causing severe pollution and posing significant potential threats to human health. Polylactic acid (PLA) and Cr are among widely used bioplastic and heavy metal, respectively, both capable of contaminating water sources through corresponding pathways and posing substantial risks to human health. Nanoplastics can act as carriers for heavy metals, thereby enhancing their bioaccumulation and toxicity. Therefore, this study investigated the effects of combined exposure to Cr(VI) and PLA NPs on mice kidneys and its potential mechanisms. Results indicated that exposure to PLA NPs alone did not exhibit significant toxic effects on the kidneys. However, combined exposure to Cr(VI) and PLA NPs caused severe kidney damage in mice. This indirectly suggests that Cr(VI) and PLA NPs exhibit synergistic toxicity rather than simple additive effects. Furthermore, combined exposure exacerbated the toxic mechanism by inducing mitochondrial damage and excessive reactive oxygen species (ROS) production, thereby triggering mitophagy. Overactivated mitophagy exacerbated lipid peroxidation by releasing free iron, thereby amplifying ROS-mediated ferroptosis. This study investigates the synergistic renal toxicity of Cr(VI) and PLA NPs, providing scientific evidence for the combined toxicity mechanism of exposure to MNPs and heavy metals.

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