title: Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.
abstract: Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations.
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Ji
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ku
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhu
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ning
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Guangke
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China. Electronic address: sangnan@sxu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013829:Thiadiazines / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D007306:Insecticides; D017382:Reactive Oxygen Species; D013829:Thiadiazines; C083997:buprofezin
keywords: Buprofezin; Energy metabolism; Hepatic toxicity; Reactive oxygen species (ROS)