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

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, we investigated the synergistic cardiotoxic effects of PLA-NPLs and SiNPs in male C57BL/6J mice. The results revealed that compared with single exposure,co-exposure to PLA-NPLs and SiNPs would significantly aggravate cardiotoxicity probably by inducing cardiac contractile dysfunction and remodeling. This cardiotoxicity was associated with inhibition of the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which impaired mitochondrial homeostasis, induced oxidative stress, and ultimately triggered cardiomyocyte apoptosis. Meanwhile, the AMPK activator Metformin and the mitochondria targeted Reactive Oxygen Species (ROS) scavenger 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 provide mechanistic insights for the synergistic toxicity of food contaminants in mammalian systems.