Polystyrene Nanoplastics and Cadmium Co-Exposure Accelerates Mitochondrial Autophagy Mediated by HSP60-SIRT3-SOD2 Signaling Pathway in Primary Duck Embryo Hepatocytes

J Agric Food Chem. 2026 Mar 18;74(10):8720-8733. doi: 10.1021/acs.jafc.5c12247. Epub 2026 Mar 5.

Abstract

Microplastics (MPs) in the environment frequently act as a medium to adsorb heavy metals and antibiotics. This combined exposure often has a greater effect on animal toxicity than exposure alone. However, there is a paucity of research focusing on the combined toxicity of nanoplastics (NPs) and heavy metals when coexposed to hepatocytes in poultry. In this study, the effects of PS-NPs (0.08 μm, 10 μg/mL) and cadmium chloride (CdCl2) (4 μg/mL) on duck hepatocytes and their mechanisms were observed using primary duck embryo hepatocytes (PDEH) cells as an in vitro model. The results demonstrated that Cd exposure exacerbated the accumulation of PS-NPs in PDEH cells, likely due to the formation of pores on the cell membrane surface. The addition of the antioxidant N-Acetyl-l-cysteine (NAC) significantly reduced the uptake of PS-NPs by PDEH cells. PDEH cells in the coexposed group exhibited significantly abnormal morphology and diminished cell number and survival rate. Furthermore, exposure to PS-NPs exacerbated Cd-mediated oxidative stress and mitochondrial autophagy damage in duck hepatocytes. The restoration of these injuries was observed in response to intervention with the SIRT3 activator (NRCL, 2 ng/mL). Immunoprecipitation experiments demonstrated that the SIRT3 protein interacted with the SOD2 protein. The present study found that co-exposure of PS-NPs+Cd induced mitochondrial autophagy in PDEH cells, which may be mediated by the HSP60/SIRT3/SOD2 signaling axis. It is hoped that these findings will provide new ideas for combating the mechanism of microplastics and Cd-induced hepatotoxicity in poultry.

Keywords: SIRT3; cadmium; mitochondrial autophagy; nanoplastics; primary duck embryo hepatocytes.

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Cadmium* / toxicity
  • Ducks* / embryology
  • Ducks* / metabolism
  • Hepatocytes* / cytology
  • Hepatocytes* / drug effects
  • Hepatocytes* / metabolism
  • Microplastics* / toxicity
  • Mitochondria* / drug effects
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Nanoparticles / toxicity
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Sirtuin 3* / genetics
  • Sirtuin 3* / metabolism
  • Superoxide Dismutase* / genetics
  • Superoxide Dismutase* / metabolism

Substances

  • Cadmium
  • Superoxide Dismutase
  • Sirtuin 3
  • Microplastics