Multi-Omics Alterations in Rat Kidneys upon Chronic Glyphosate Exposure

Area of Science:

• Toxicology
• Renal Function
• Molecular Biology

Background:

• Glyphosate-based herbicides (GBHs) are widely used, but their molecular impact on kidney function is not fully understood.
• The kidney is vulnerable to xenobiotic damage due to its excretory role.
• Previous studies suggest GBHs can cause kidney injury.

Purpose of the Study:

• To investigate N-glycomics and proteomics changes in the kidney after chronic GBH exposure.
• To elucidate the molecular mechanisms of glyphosate-induced kidney damage.
• To identify potential sex-specific differences in GBH nephrotoxicity.

Main Methods:

• Analysis of kidney tissues from male and female rats exposed to GBHs.
• Liquid chromatography-tandem mass spectrometry for N-glycomics and proteomics.
• Identification of altered N-glycan structures and protein expression profiles.

Main Results:

• Significant changes in kidney N-glycan composition, particularly fucosylated and sialofucosylated types.
• Activation of immune signaling and inflammatory pathways (e.g., neutrophil degranulation, integrin signaling).
• Upregulation of transcription regulators (IL-6, STAT3, NFE2L2) indicating inflammation and oxidative stress.
• Female rats displayed more pronounced alterations, suggesting higher susceptibility.

Conclusions:

• Chronic GBH exposure induces significant N-glycomic and proteomic changes in the kidney.
• GBH exposure activates immune responses, inflammation, and oxidative stress pathways.
• Sex-specific differences in response suggest females may be more vulnerable to GBH nephrotoxicity, potentially involving carcinogenic processes.