Work

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

Year: 2026

Type: article

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.

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s626343