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Spinetoram confers its cytotoxic effects by inducing AMPK/mTOR-mediated autophagy and oxidative DNA damage

Yang Zhang1, Wei Guo2, Hui Chen1

  • 1Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

Ecotoxicology and Environmental Safety
|August 6, 2019
PubMed

Insights

Spinetoram, a widely used biopesticide, harms human liver cells by disrupting autophagy and causing DNA damage. This research highlights potential health risks associated with spinetoram residue in food.

Area of Science:

  • Toxicology
  • Cell Biology
  • Biochemistry

Background:

  • Spinetoram is a prevalent biopesticide, raising concerns about potential human health effects due to food residues.
  • The liver is a primary target for pesticide toxicity, but spinetoram's specific impact on human liver cells is not well understood.

Purpose of the Study:

  • To investigate the in vitro cytotoxic effects of spinetoram on human liver HepG2 cells.
  • To elucidate the molecular mechanisms underlying spinetoram-induced cytotoxicity in liver cells.

Main Methods:

  • Exposure of human liver HepG2 cells to spinetoram.
  • Assessment of cell proliferation, mitochondrial membrane potential, and DNA damage (8-oxodG).
  • Analysis of autophagy-related proteins (LC3-II, Beclin-1, p62) and AMPK/mTOR signaling pathway activation.

Main Results:

  • Spinetoram inhibited HepG2 cell proliferation and induced oxidative DNA damage.
  • Decreased mitochondrial membrane potential and altered autophagy markers (LC3-II conversion, Beclin-1 accumulation, p62 degradation) were observed.
  • Changes in AMPK/mTOR phosphorylation indicated involvement of this pathway in spinetoram toxicity.

Conclusions:

  • Spinetoram exhibits significant cytotoxicity in human liver cells.
  • The toxicity mechanism involves the induction of autophagy via the AMPK/mTOR pathway and oxidative DNA damage.
  • Findings provide a basis for understanding spinetoram's toxicity and assessing its safety for human consumption.
Keywords:
AMPK/mTOR-mediated autophagyCytotoxic effectsMitochondrial dysfunctionOxidative DNA damageSpinetoram

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