title: Multilevel evaluations of potential liver injury of bifenthrin.
abstract: The widespread use of pesticides, such as pyrethroids, increases health risks to non-target organisms. The potential toxicity of pyrethroids to the liver remains unclear and could be easily overlooked if only the common clinical indicators of liver disease are examined. In the present study, BALB/c mice were given intraperitoneal injections of 0, 2, 4, or 8 mg/kg bifenthrin (BF) for 7 days. The potential liver injury of BF and its underlying mechanism were then investigated through multilevel evaluations. Histological analyses and serum enzyme activities showed no obvious clinical evidence of liver damage. Oxidative stress was induced and caspases were activated in response to increased BF concentrations. Exposure to BF also significantly altered the expression levels of mitochondrial apoptosis-related genes in dose-dependent relationships. The microarray results showed that BF could disturb the metabolic profile and extensively induce genes related to oxidative stress, including the cytochrome P450 family, glutathione peroxidases, glutathione s-transferases and kinases. In the in vivo model, BF induced liver injury through caspase-mediated mitochondrial-dependent cell death, a process that is closely related to oxidative stress, even in the absence of classical clinical biomarkers of liver dysfunction. The results of this study suggest that classical evaluations are not adequate for liver toxicity of pyrethroids, and highlight the need for more comprehensive assessment of health risks of these widely used pesticides.
authors.affiliation: Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai 200241, China; School of Ecological and Environmental Science, East China Normal University, Shanghai 200241, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Meiya
authors.initials: M
authors.lastname: Lu
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Peixue
authors.initials: P
authors.lastname: Zhou
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: zhaomr@zjut.edu.cn.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004798:Enzymes / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008658:Inactivation, Metabolic / Q000235:genetics*; D007306:Insecticides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011722:Pyrethrins / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D004798:Enzymes; D007306:Insecticides; D011722:Pyrethrins; C099952:bifenthrin; D020169:Caspases
keywords: Bifenthrin; Cell death; Liver injury; Metabolism; Microarray