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Inhibition of AMPK Signaling Pathway Mediates Cardiotoxicity Induced by Co-Exposure to Polylactic Acid Nanoplastics and Silica Nanoparticles.

Created on 26 Jul 2026

Authors

Yifan Dai, Yudeng Wang, Xinrong Wang, Yuankun Zhou, Hengyi Xu

Published in

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. Pages 116287. Jul 25, 2026. Epub Jul 25, 2026.

Abstract

Emerging evidence suggests that synergistic toxic effects are induced upon co-exposure to different food contaminants. Considering that polylactic acid nanoplastics (PLA-NPLs) and synthetic amorphous silica (SAS) are widely used in food industry, it is of great importance to investigate whether the nano-scale derivatives, PLA-NPLs and silica nanoparticles (SiNPs), would exhibit synergistic cardiotoxic effects. Here in, we investigated the synergistic cardiotoxic effects of PLA-NPLs and SiNPs in male C57BL/6J mice. The results revealed that compared with single exposure, the synergistic exposure to PLA-NPLs and SiNPs would significantly aggravate cardiotoxicity probably by inducing cardiac contractile dysfunction and remodeling. This cardiotoxicity could be attributed to Adenosine Monophosphate-activated Protein Kinase (AMPK) signaling pathway inhibition since AMPK signaling pathway inhibition would further impair mitochondrial homeostasis and then induce redox dysregulation finally triggering cardiomyocyte apoptosis. Meanwhile, the AMPK activator Metformin and the mitochondria targeted Reactive Oxygen Species (ROS) scavenger mitochondria-targeted 2,2,6,6-tetramethylpiperidine-1-oxyl (Mito-TEMPO) were further used to confirm the involvement of AMPK signaling and ROS. In summary, co-exposure to PLA-NPLs and SiNPs would induce more severe cardiac injury and offer mechanistic clues for the synergistic toxicity of food contaminants in mammalian systems.

PMID:
42501960
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.

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