Activation of the N ‐methyl‐d‐aspartate receptor is involved in glyphosate‐induced renal proximal tubule cell apoptosis

In this study, we treated a human renal proximal tubule cell line (HK‐2) with glyphosate for 24 hours at concentrations of 0, 20, 40 and 60 μm. Glyphosate was found to reduce cell viability and induce apoptosis and oxidative stress in a dose ‐dependent manner. Because the chemical structures of glyphosate and those of its metabolite AMPA are similar to glycine and glutamate, which are agonists of theN‐methyl‐d‐aspartate receptor (NMDAR), we investigated the potential role of the NMDAR pathway in mediating the proapoptotic effect of glyphosate on proximal tubule cells. We found that NMDAR1 expression, as well as intracellular Ca2+ ([Ca2+]i) and reactive oxygen species (ROS) levels, increased after glyphosate treatment. Blocking NMDAR attenuated glyphosate ‐induced upregulation of [Ca2+]i and ROS levels as well as apoptosis. Meanwhile, inhibition of [Ca2+]i reduced glyphosate ‐induced ROS and apoptosis, and inhibition of ROS alleviated glyphosate‐induced apoptosis. In mice exposed to 400 mg/kg glyphosate, the urine low molecular weight protein levels started to increase from day 7. Upregulation of apoptosis and NMDAR1 expression in renal proximal tubule epithelium a nd an imbalance of oxidant and antioxidative products were observed. These results strongly suggest that activation of the NMDAR1 pathway, together with its downstream [Ca2+]i and oxidative stress, is involved in glyphosate ‐induced renal proximal tubule epithelium apoptosis.

Source: Journal of Applied Toxicology - July 9, 2019 Category: Toxicology Authors: Hui Gao, Jing Chen, Fan Ding, Xin Chou, Xiaoyan Zhang, Yi Wan, Jianying Hu, Qing Wu Tags: RESEARCH ARTICLE Source Type: research