title: Carbendazim has the potential to induce oxidative stress, apoptosis, immunotoxicity and endocrine disruption during zebrafish larvae development.
abstract: Increasing evidence have suggested deleterious effects of carbendazim on reproduction, apoptosis, immunotoxicity and endocrine disruption in mice and rats, however, the developmental toxicity of carbendazim to aquatic organisms remains obscure. In the present study, we utilized zebrafish as an environmental monitoring model to characterize the effects of carbendazim on expression of genes related to oxidative stress, apoptosis, immunotoxicity and endocrine disruption during larval development. Different trends in gene expression were observed upon exposing the larvae to 4, 20, 100, and 500 μg/L carbendazim for 4 and 8d. The mRNA levels of catalase, glutathione peroxidase and manganese superoxide dismutase (CAT, GPX, and Mn/SOD) were up-regulated after exposure to different concentrations of carbendazim for 4 or 8d. The up-regulation of p53, Apaf1, Cas8 and the down-regulation of Bcl2, Mdm2, Cas3 in the apoptosis pathway, as well as the increased expression of cytokines and chemokines, including CXCL-C1C, CCL1, IL-1b, IFN, IL-8, and TNFα, suggested carbendazim might trigger apoptosis and immune response during zebrafish larval development. In addition, the alteration of mRNA expression of VTG, ERα, ERβ1, ERβ2, TRα, TRβ, Dio1, and Dio2 indicated the potential of carbendazim to induce endocrine disruption in zebrafish larvae. These data suggested that carbendazim could simultaneously induce multiple responses during zebrafish larval development, and bidirectional interactions among oxidative stress, apoptosis pathway, immune and endocrine systems might be present.
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China. Electronic address: jinhuajjh@sina.com.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
authors.forename: Shenggan
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: An
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Cai
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China; Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China. Electronic address: wu_cx@yahoo.com.cn.
authors.forename: Changxing
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D002219:Carbamates / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005659:Fungicides, Industrial / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D015027:Zebrafish
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D016207:Cytokines; D052244:Endocrine Disruptors; D005659:Fungicides, Industrial; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D007453:Iodide Peroxidase; C006698:carbendazim
keywords: Apoptosis; Carbendazim; Endocrine disruption; Immunotoxicity; Oxidative stress; Zebrafish larvae