Pyrethrin II impairs mitochondrial potential through ROS and MAPK pathways in HT‑22 cells

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Pyrethrin II is a common insecticide component.
• Its neurotoxic mechanisms, particularly in hippocampal neurons, require elucidation.

Purpose of the Study:

• To investigate Pyrethrin II-induced hippocampal neuronal injury.
• To explore the roles of reactive oxygen species (ROS) and the MAPK pathway in this injury.

Main Methods:

• HT-22 cells were treated with Pyrethrin II.
• Assays included CCK-8, transcriptomics, ROS measurement, Western blotting, JC-1 staining, TUNEL, cleaved caspase-3, EdU, and PCNA.

Main Results:

• Pyrethrin II induced dose-dependent ROS production and MAPK pathway dysregulation (JNK/p38 activation, ERK suppression).
• ROS overproduction led to decreased mitochondrial membrane potential and apoptosis.
• ERK suppression impaired cell proliferation, while JNK activation promoted apoptosis.

Conclusions:

• Pyrethrin II causes neurotoxicity via ROS-mediated disruption of the JNK/ERK axis, affecting the proliferation-apoptosis balance.
• This mechanism involves mitochondrial dysfunction and cell death.
• Targeting this pathway requires caution due to essential physiological roles of JNK and ERK.