Oxyfluorfen exposure can cause acute kidney injury by promoting ROS-induced oxidative stress and inflammation in zebrafish

Nephrotoxicity of oxyfluorfen to vertebrates remains unclear despite its wide use as a herbicide. In order to further study its nephrotoxicity and its underlying mechanism, we used human embryonic kidney cells and zebrafish to explore. HEK293T cells were exposed to 2, 4, 6 μg/mL oxyfluorfen for 24 h in vitro, and zebrafish were exposed to 0.4, 0.8, 1.2 mg/L oxyfluorfen for 72 h in vivo. We found that oxyfluorfen inhibits cell migration and induces oxidative stress and apoptosis, causing kidney damage or nephrotoxicity in embryonic and adult zebrafish. Oxyfluorfen triggered inflammation in zebrafish and causing severe periorbital and body edema in embryos. Oxyfluorfen induced the secretion of kidney injury markers, including urea nitrogen (BUN), creatinine (CR), and β-n-acetyl-glucosaminidase (NAG) in zebrafish. Additionally, oxyfluorfen affected the homeostasis of oxidant and antioxidant systems, leading to reactive oxygen species (ROS) overload. Oxyfluorfen also damaged the glomerular podocytes and induced apoptosis of proximal tubules, which is harmful to normal body function and the renal filtration system. These results indicate that oxyfluorfen is a potential environmental hazard that can cause severe kidney injury and affect the health of organisms.