Commercial glyphosate formulations exceed active ingredient toxicity via mitochondrial ROS and transcriptomic...

Area of Science:

• Environmental Toxicology
• Cellular Stress Response
• Biochemistry

Background:

• Glyphosate (GLY) is a widely used pesticide.
• Glyphosate-based herbicides (GBHs) may pose greater toxicity than GLY alone.

Purpose of the Study:

• To compare the cellular and transcriptomic responses of HepG2 cells to GLY and a commercial GBH.
• To investigate the distinct toxicological mechanisms of GBHs.

Main Methods:

• Utilized HepG2 cells with mitochondrial-targeted Hyper7 for H₂O₂ monitoring.
• Performed RNA sequencing to analyze transcriptomic alterations.
• Assessed protein levels of PRDX3.

Main Results:

• GBH exposure significantly increased mitochondrial H₂O₂ levels and impaired redox homeostasis.
• GBH induced endoplasmic reticulum (ER) stress and unfolded protein response.
• GBH upregulated genes involved in autophagy, apoptosis, and altered metabolic pathways.

Conclusions:

• GBHs trigger complex cellular stress and metabolic changes distinct from GLY.
• Assessing full GBH formulations is crucial for accurate health risk assessment.
• GBHs present a unique toxicological profile compared to glyphosate alone.