Spinetoram-Induced Potential Neurotoxicity through Autophagy Mediated by Mitochondrial Damage

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Spinetoram is a semi-synthetic insecticide targeting insect acetylcholine receptors.
• Its neurotoxicity in humans remains understudied despite agricultural use.

Purpose of the Study:

• To investigate the neurotoxic effects of spinetoram on human neuroblastoma cells (SH-SY5Y) and zebrafish.
• To elucidate the mechanisms underlying spinetoram-induced neurotoxicity, focusing on mitochondrial function and autophagy.

Main Methods:

• Exposure of SH-SY5Y cells to varying spinetoram concentrations (5–20 μM).
• Assessment of cell viability, oxidative stress, mitochondrial membrane potential (ΔΨm), and ATP synthesis.
• Analysis of autophagy markers (LC3, p62, beclin-1) and AMPK/mTOR signaling pathways.
• Neurobehavioral observation and autophagy analysis in spinetoram-exposed zebrafish (5–20 μg/mL).

Main Results:

• Spinetoram inhibited cell viability, induced oxidative stress, and caused mitochondrial dysfunction (ΔΨm collapse, mPTP opening, decreased ATP, Ca2+ overload) in SH-SY5Y cells.
• Spinetoram triggered autophagy via the AMPK/mTOR pathway in both cell cultures and zebrafish.
• Zebrafish exhibited neurobehavioral deficits, including reduced movement and tail swings, correlating with observed autophagy.

Conclusions:

• Spinetoram exposure induces significant neurotoxicity in vitro and in vivo.
• Mitochondrial damage and subsequent autophagy are key mechanisms in spinetoram's neurotoxic action.
• Findings provide crucial data for spinetoram safety assessments in humans.