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Peer-reviewedCC BY-NCDrug design, development and therapy

Chronic Glyphosate Exposure Induces Spleen Injury via ROS-Mitochondrial Pathway, Accompanied by Changes in Inflammation and Apoptosis Related to RHOA / ROCK Pathway.

  • Yinghua Ma1
  • Zhiyao Liu1
  • Zifa Li2,3,4
  • Minghui Hu1
  • Huaxue Zhang2,3,4
  • Yixuan Wang2,3,4
  • Haiyu Zhang2,3,4
  • Xiaowen Zhang2,3,4
  • Yuezhi Feng2,3,4
  • Meiyuan Li2,3,4
  • LiDan Wu2,3,4,5
  • Hao Zhang2,3,4
2 more authors
  • Sheng Wei2,3,4
  • Xinyu Wang2,3,4
5 affiliations
  1. 1Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, People's Republic of China.
  2. 2Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji'nan, People's Republic of China.
  3. 3Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji'nan, People's Republic of China.
  4. 4Shandong Provincial Engineering Research Center for the Prevention and Treatment of Major Brain Diseases with Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji'nan, People's Republic of China.
  5. 5Institute of Pharmaceutical Research, Shandong University of Traditional Chinese Medicine, Ji'nan, People's Republic of China.
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Abstract

Background

Glyphosate is the most widely used broad‑spectrum herbicide worldwide. The potential health risks associated with chronic low‑dose glyphosate exposure have attracted growing attention in environmental and public health research, while its toxic effects on the spleen remain poorly understood.Methods

Male C57BL/6J mice were used to establish low and high‑dose glyphosate long‑term exposure models. HE-staining assessed spleen pathology. ELISA/q-PCR detected inflammatory factors. DHE fluorescence probe and MDA assay were applied to evaluate oxidative-stress status. Transmission electron microscopy was used to observe mitochondrial ultrastructural alterations. TUNEL staining and Western blot were performed to detect splenocyte apoptosis and the expression of RHOA/ROCK-related and apoptosis-associated proteins. Network pharmacology and molecular docking were utilized to predict potential targets.Results

Glyphosate exposure can induce pathological damage of spleen in mice. It elevated pro-inflammatory factors, ROS and MDA, while down-regulating NQO1/HO1, triggering oxidative stress and mitochondrial injury. In addition, glyphosate exposure was accompanied by up-regulation of RHOA/ROCK pathway proteins, disordered expression of apoptosis-related proteins, and increased apoptosis of spleen cells. Under the conditions of this experiment, there was no significant difference in body weight and spleen index between the groups.Discussion

Chronic glyphosate exposure can inhibit the NQO1/HO1 antioxidant pathway, induce oxidative stress and mitochondrial structural damage, accompanied by inflammatory response, apoptosis and RHOA/ROCK pathway-related protein expression changes, resulting in spleen tissue damage in mice. This study provides an experimental basis for the toxicity risk assessment and potential intervention target screening of glyphosate.

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Cite

BibTeXRIS
BibTeX
@article{ma2026chronic,
  title = {{Chronic Glyphosate Exposure Induces Spleen Injury via ROS-Mitochondrial Pathway, Accompanied by Changes in Inflammation and Apoptosis Related to RHOA / ROCK Pathway.}},
  author = {Yinghua Ma and Zhiyao Liu and Zifa Li and Minghui Hu and Huaxue Zhang and Yixuan Wang and Haiyu Zhang and Xiaowen Zhang and Yuezhi Feng and Meiyuan Li and LiDan Wu and Hao Zhang and Sheng Wei and Xinyu Wang},
  journal = {Drug design, development and therapy},
  year = {2026},
  month = oct,
  doi = {10.2147/dddt.s626343},
  url = {https://europepmc.org/article/MED/42974494},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Chronic Glyphosate Exposure Induces Spleen Injury via ROS-Mitochondrial Pathway, Accompanied by Changes in Inflammation and Apoptosis Related to RHOA / ROCK Pathway.
AU  - Yinghua Ma
AU  - Zhiyao Liu
AU  - Zifa Li
AU  - Minghui Hu
AU  - Huaxue Zhang
AU  - Yixuan Wang
AU  - Haiyu Zhang
AU  - Xiaowen Zhang
AU  - Yuezhi Feng
AU  - Meiyuan Li
AU  - LiDan Wu
AU  - Hao Zhang
AU  - Sheng Wei
AU  - Xinyu Wang
PY  - 2026
DA  - 2026/10/29
JO  - Drug design, development and therapy
DO  - 10.2147/dddt.s626343
UR  - https://europepmc.org/article/MED/42974494
AB  - Background  Glyphosate is the most widely used broad‑spectrum herbicide worldwide. The potential health risks associated with chronic low‑dose glyphosate exposure have attracted growing attention in environmental and public health research, while its toxic effects on the spleen remain poorly understood.Methods  Male C57BL/6J mice were used to establish low and high‑dose glyphosate long‑term exposure models. HE-staining assessed spleen pathology. ELISA/q-PCR detected inflammatory factors. DHE fluorescence probe and MDA assay were applied to evaluate oxidative-stress status. Transmission electron microscopy was used to observe mitochondrial ultrastructural alterations. TUNEL staining and Western blot were performed to detect splenocyte apoptosis and the expression of RHOA/ROCK-related and apoptosis-associated proteins. Network pharmacology and molecular docking were utilized to predict potential targets.Results  Glyphosate exposure can induce pathological damage of spleen in mice. It elevated pro-inflammatory factors, ROS and MDA, while down-regulating NQO1/HO1, triggering oxidative stress and mitochondrial injury. In addition, glyphosate exposure was accompanied by up-regulation of RHOA/ROCK pathway proteins, disordered expression of apoptosis-related proteins, and increased apoptosis of spleen cells. Under the conditions of this experiment, there was no significant difference in body weight and spleen index between the groups.Discussion  Chronic glyphosate exposure can inhibit the NQO1/HO1 antioxidant pathway, induce oxidative stress and mitochondrial structural damage, accompanied by inflammatory response, apoptosis and RHOA/ROCK pathway-related protein expression changes, resulting in spleen tissue damage in mice. This study provides an experimental basis for the toxicity risk assessment and potential intervention target screening of glyphosate.
SN  - 1177-8881
ER  -