2. Academic Validation
  3. Glyphosate promotes calcium oxalate crystal-induced renal injury by modulating the PI3K/Akt-mediated mechanism

Glyphosate promotes calcium oxalate crystal-induced renal injury by modulating the PI3K/Akt-mediated mechanism

  • Ecotoxicol Environ Saf. 2026 Mar 15:313:119962. doi: 10.1016/j.ecoenv.2026.119962.
Guoxiang Li 1,  Junfeng Yao 1,  Xincheng Yi 1,  Ming Liu 1,  Defeng Ge 1,  Junzhi Zhang 1,  Yang Chen 2,  Zongyao Hao 3,  Xudong Shen 4
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China.
  • 2 Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. Electronic address: [email protected].
  • 3 Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. Electronic address: [email protected].
  • 4 Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. Electronic address: [email protected].
PMID: 41797104 DOI: 10.1016/j.ecoenv.2026.119962
Abstract

The increasing global prevalence of nephrolithiasis represents a significant public health concern. However, the role of environmental contaminants such as glyphosate remains unclear. Herein, epidemiological analysis, network toxicology, and experimental validation were integrated to investigate this association. Cross-sectional analysis of NHANES data demonstrated a significant dose-dependent relationship between urinary glyphosate levels and nephrolithiasis prevalence. Each unit increase in log-transformed glyphosate concentration was associated with a 25% increase in nephrolithiasis risk (OR = 1.25, 95% CI: 1.06-1.47). Network toxicology combined with molecular docking and dynamics simulations identified the PI3K/Akt signaling pathway as a potential target, showing stable binding of glyphosate to core proteins. This mechanism was functionally validated in vivo and in vitro, indicating that glyphosate co-exposure exacerbated calcium oxalate-induced renal tubular injury, oxidative stress, and Apoptosis through suppression of the PI3K/Akt pathway. This effect was significantly reversed by pathway agonism. Collectively, this study provides the first integrative evidence identifying environmental glyphosate exposure as a novel risk factor for nephrolithiasis. Furthermore, inhibition of the PI3K/Akt pathway was delineated as the primary underlying mechanism, offering a conceptual framework for future preventive and therapeutic strategies.

Keywords

Glyphosate; Kidney stones; Molecular docking; Network Toxicology; PI3K/AKT signaling pathway.

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