# Multi-Omics Alterations in Rat Kidneys upon Chronic Glyphosate Exposure

## TL;DR

This study finds that chronic exposure to glyphosate-based herbicides alters kidney N-glycans and proteins, causing inflammation and immune responses, with females being more affected.

## Contribution

The study reveals sex-specific molecular alterations in rat kidneys due to chronic glyphosate exposure, linking it to immune activation and inflammation.

## Key findings

- Chronic glyphosate exposure alters N-glycan composition, especially fucosylated and sialofucosylated types in rat kidneys.
- Proteomic analysis shows activation of immune and inflammatory pathways, including neutrophil degranulation and MHC class I antigen presentation.
- Female rats show more pronounced changes in N-glycans and proteins, indicating higher susceptibility to glyphosate-induced kidney damage.

## Abstract

Clinical studies have linked glyphosate exposure to substantial morbidity, with acute kidney injury occurring in some cases. Although the toxic effects of glyphosate-based herbicides (GBHs) have been reported in several studies, their molecular impact on renal function remains poorly understood. Given the kidney’s critical role in excretion, it is particularly susceptible to damage from xenobiotic exposure. In this study, we aim to identify N-glycomics and proteomics change in the kidney following chronic GBH exposure, to better understand the mechanisms behind glyphosate-induced kidney damage. Kidney tissues from female and male rats were analyzed using liquid chromatography–tandem mass spectrometry. The results revealed notable changes in the N-glycan composition, particularly in the fucosylated and sialofucosylated N-glycan types. The proteomic analysis revealed the activation of immune signaling and inflammatory pathways, including neutrophil degranulation, integrin signaling, and MHC class I antigen presentation. Transcription regulators, such as IL-6, STAT3, and NFE2L2, were upregulated, indicating a coordinated inflammatory and oxidative stress response. Sex-specific differences were apparent, with female rats exhibiting more pronounced alterations in both the N-glycan and protein expression profiles, suggesting a higher susceptibility to GBH-induced nephrotoxicity. These findings provide new evidence that chronic GBH exposure may trigger immune activation, inflammation, and potentially carcinogenic processes in the kidney.