WU Yuanzhao, ZHANG Anhui, XU Fan, ZHENG Zhongyu, YING Jianbo, WANG Binjie, WANG Jiye, YAO Weixuan. Neurodevelopmental toxicity of bromadiolone to early-staged zebrafish[J]. Journal of Environmental and Occupational Medicine, 2022, 39(10): 1154-1159. DOI: 10.11836/JEOM21576
Citation: WU Yuanzhao, ZHANG Anhui, XU Fan, ZHENG Zhongyu, YING Jianbo, WANG Binjie, WANG Jiye, YAO Weixuan. Neurodevelopmental toxicity of bromadiolone to early-staged zebrafish[J]. Journal of Environmental and Occupational Medicine, 2022, 39(10): 1154-1159. DOI: 10.11836/JEOM21576

Neurodevelopmental toxicity of bromadiolone to early-staged zebrafish

Funds: This study was funded.
More Information
  • Corresponding author:

    YAO Weixuan, E-mail: yaoweixuan@zjjcxy.cn

  • Received Date: December 05, 2021
  • Accepted Date: June 04, 2022
  • Available Online: February 14, 2023
  • Background 

    Bromadiolone is the second-generation anticoagulant rodenticide widely used all over the world. Exposure to bromadiolone in early life stage can lead to neurodevelopmental toxicity, but its toxic mechanism of neurodevelopment is not clear so far.

    Objective 

    To investigate the developmental neurotoxicity and mechanism of bromadiolone to zebrafish embryos.

    Methods 

    Zebrafish embryos were randomly divided into four groups: a solvent control group (dimethylsulphoxide) and three bromadiolone exposure groups (0.39, 0.78, and 1.18 mg·L−1). The exposure period was from 4 h to 120 h post-fertilization. The number of spontaneous movement per minute was recorded at 24 h post-treatment. The locomotor ability of zebrafish larvae and the activity of acetylcholinesterase (AChE) were tested at 120 h post-treatment. The relative expression levels of neurodevelopment-related genes (elavl3, gap43, mbp, and syn2a) were measured by fluorescence quantitative PCR.

    Results 

    Compared with the control group, the number of spontaneous movement per minute at 24 h decreased significantly in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05). Compared with the control group, the total distance travelled of the zebrafish larvae in the 0.78 and 1.18 mg·L−1 bromadiolone exposure groups decreased by 60% and 69% respectively (P<0.05, P<0.01), and the total movement time decreased by 34% and 65% respectively (P<0.05, P<0.01). The AChE activity in the 1.18 mg·L−1 bromadiolone exposure group increased by 36% when compared with the control group (P<0.05). The fluorescence quantitative PCR results showed that compared with the control group, the expression levels of neurodevelopment-related genes elavl3, syn2a, and mbp were significantly down-regulated by 66%, 69%, and 65% in the 1.18 mg·L−1 bromadiolone exposure group respectively (P<0.01), the expression level of gap43 was up-regulated by 56% in the 0.78 mg·L−1 bromadiolone exposure group (P<0.01) and down-regulated by 34% in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05).

    Conclusion 

    Bromadiolone exposure could inhibit spontaneous movement and locomotive behavior, down-regulate the expression levels of neurodevelopment-related genes, hinder the release of neurotransmitters, and result in neurodevelopmental toxicity in the early-staged zebrafish.

  • [1]
    BERNY P, VELARDO J, PULCE C, et al. Prevalence of anticoagulant rodenticide poisoning in humans and animals in France and substances involved[J]. Clin Toxicol (Phila), 2010, 48(9): 935-941.
    [2]
    BERTERO A, CHIARI M, VITALE N, et al. Types of pesticides involved in domestic and wild animal poisoning in Italy[J]. Sci Total Environ, 2020, 707: 136129. doi: 10.1016/j.scitotenv.2019.136129
    [3]
    HROMADA R, MIŇO I, KORYTÁ R, et al. Potential health risk to humans related to accumulation of brodifacoum and bromadiolone in the wheat grown on rodenticide contaminated soil[J]. Folia Vet, 2019, 63(3): 18-26. doi: 10.2478/fv-2019-0023
    [4]
    KUPPER J, GROBOSCH T, KISTLER R, et al. Bromadiolone poisoning in foxes[J]. Schweiz Arch Tierheilkd, 2006, 148(8): 405-408. doi: 10.1024/0036-7281.148.8.405
    [5]
    赵丹玭, 杨泽国, 尉志文, 等. 溴敌隆及其代谢物-苄叉丙酮在犬体内的死后分布[J]. 中国法医学杂志, 2017, 32(3): 294-297. doi: 10.13618/j.issn.1001-5728.2017.03.016

    ZHAO D P, YANG Z G, WEI Z W, et al. The postmortem distribution of bromadiolone and its metabolite-benzylideneacetone in poisoned dogs[J]. Chin J Forensic Med, 2017, 32(3): 294-297. doi: 10.13618/j.issn.1001-5728.2017.03.016
    [6]
    NOSAL D G, FEINSTEIN D L, VAN BREEMEN R B. Chiral liquid chromatography-tandem mass spectrometry analysis of superwarfarin rodenticide stereoisomers-bromadiolone, difenacoum and brodifacoum-in human plasma[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2021, 1165: 122529. doi: 10.1016/j.jchromb.2021.122529
    [7]
    ALOMAR H, CHABERT A, COEURDASSIER M, et al. Accumulation of anticoagulant rodenticides (chlorophacinone, bromadiolone and brodifacoum) in a non-target invertebrate, the slug, Deroceras reticulatum[J]. Sci Total Environ, 2018, 610-611: 576-582. doi: 10.1016/j.scitotenv.2017.08.117
    [8]
    LU A, YUAN F, YAO Y, et al. Reversible leukoencephalopathy caused by 2 rodenticides bromadiolone and fluoroacetamide: a case report and literature review[J]. Medicine (Baltimore), 2021, 100(9): e25053. doi: 10.1097/MD.0000000000025053
    [9]
    BUCKLE A P, JONES C R, RYMER D J, et al. The Hampshire-Berkshire focus of L120Q anticoagulant resistance in the Norway rat (Rattus norvegicus) and field trials of bromadiolone, difenacoum and brodifacoum[J]. Crop Prot, 2020, 137: 105301. doi: 10.1016/j.cropro.2020.105301
    [10]
    ZUO W, ZHANG X, CHANG J B, et al. Bromadiolone poisoning leading to subarachnoid haemorrhage: A case report and review of the literature[J]. Journal of clinical pharmacy and therapeutics, 2019, 44(6): 958-962. doi: 10.1111/jcpt.13005
    [11]
    WANG M, YANG Y, HOU Y, et al. Effects of bromadiolone poisoning on the central nervous system[J]. Neuropsychiatr Dis Treat, 2017, 13: 2297-2300. doi: 10.2147/NDT.S142375
    [12]
    LI R A, TALIKKA M, GUBIAN S, et al. Systems toxicology approach for assessing developmental neurotoxicity in larval zebrafish[J]. Front Genet, 2021, 12: 652632. doi: 10.3389/fgene.2021.652632
    [13]
    何梦婷, 王伟, 许洁, 等. 氧化应激参与溴乙酰胺致斑马鱼胚胎神经发育毒性[J]. 环境与职业医学, 2021, 38(6): 586-592. doi: 10.13213/j.cnki.jeom.2021.20580

    HE M T, WANG W, XU J, et al. Role of oxidative stress in neurodevelopmental toxicity of bromoacetamide in zebrafish embryos[J]. J Environ Occup Med, 2021, 38(6): 586-592. doi: 10.13213/j.cnki.jeom.2021.20580
    [14]
    BUSCHMANN J. The OECD guidelines for the testing of chemicals and pesticides[J]. Methods Mol Biol, 2013, 947: 37-56.
    [15]
    顾杰, 王宏烨, 廖振东, 等. 双酚AP和双酚AF对斑马鱼的早期神经发育毒性作用研究[J]. 环境与职业医学, 2019, 36(1): 11-16. doi: 10.13213/j.cnki.jeom.2019.18404

    GU J, WANG H Y, LIAO Z D, et al. Neurodevelopmental toxicities of bisphenol AP and bisphenol AF in early life of zebrafish[J]. J Environ Occup Med, 2019, 36(1): 11-16. doi: 10.13213/j.cnki.jeom.2019.18404
    [16]
    NERY L R, ELTZ N S, HACKMAN C, et al. Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium[J]. PLoS One, 2014, 9(9): e105862. doi: 10.1371/journal.pone.0105862
    [17]
    LIAO X, ZHANG M, ZHAO A, et al. Retrospective study of twenty-four patients with prolonged coagulopathy due to long-acting anti-vitamin K rodenticide poisoning[J]. Am J Med Sci, 2014, 347(4): 299-304. doi: 10.1097/MAJ.0b013e318291cb7d
    [18]
    赵晨曦, 王杨, 钱秋慧, 等. 三氯卡班环境暴露对斑马鱼神经行为的影响[J]. 中国环境科学, 2022, 42(1): 456-464. doi: 10.3969/j.issn.1000-6923.2022.01.047

    ZHAO C X, WANG Y, QIAN Q H, et al. Effects of environmental exposure to triclocarban on the neurobehavior of zebrafish (Danio rerio)[J]. China Environ Sci, 2022, 42(1): 456-464. doi: 10.3969/j.issn.1000-6923.2022.01.047
    [19]
    BASNET R M, ZIZIOLI D, TAWEEDET S, et al. Zebrafish larvae as a behavioral model in neuropharmacology[J]. Biomedicines, 2019, 7(1): 23. doi: 10.3390/biomedicines7010023
    [20]
    PULLAGURI N, GROVER P, ABHISHEK S, et al. Triclosan affects motor function in zebrafish larva by inhibiting ache and syn2a genes[J]. Chemosphere, 2021, 266: 128930. doi: 10.1016/j.chemosphere.2020.128930
    [21]
    CHEN L, YU K, HUANG C, et al. Prenatal transfer of polybrominated diphenyl ethers (PBDEs) results in developmental neurotoxicity in zebrafish larvae[J]. Environ Sci Technol, 2012, 46(17): 9727-9734. doi: 10.1021/es302119g
    [22]
    XU H, SHAO X, ZHANG Z, et al. Effects of di-n-butyl phthalate and diethyl phthalate on acetylcholinesterase activity and neurotoxicity related gene expression in embryonic zebrafish[J]. Bull Environ Contam Toxicol, 2013, 91(6): 635-639. doi: 10.1007/s00128-013-1101-9
    [23]
    MÜLLER C, BAUER N M, SCHÄFER I, et al. Making myelin basic protein-from mRNA transport to localized translation[J]. Front Cell Neurosci, 2013, 7: 169.
    [24]
    FAN C Y, COWDEN J, SIMMONS S O, et al. Gene expression changes in developing zebrafish as potential markers for rapid developmental neurotoxicity screening[J]. Neurotoxicol Teratol, 2010, 32(1): 91-98. doi: 10.1016/j.ntt.2009.04.065
    [25]
    王伟, 何梦婷, 许洁, 等. 芳香烃受体介导双酚A致斑马鱼胚胎发育毒性[J]. 环境与职业医学, 2021, 38(4): 342-349. doi: 10.13213/j.cnki.jeom.2021.20505

    WANG W, HE M T, XU J, et al. Aryl hydrocarbon receptor-mediated developmental toxicity in zebrafish embryos induced by bisphenol A[J]. J Environ Occup Med, 2021, 38(4): 342-349. doi: 10.13213/j.cnki.jeom.2021.20505
    [26]
    CHENG R, JIA Y, DAI L, et al. Tris (1, 3-dichloro-2-propyl) phosphate disrupts axonal growth, cholinergic system and motor behavior in early life zebrafish[J]. Aquat Toxicol, 2017, 192: 7-15. doi: 10.1016/j.aquatox.2017.09.003
  • Related Articles

    [1]ZENG Fanzhao, JIN Meng, SHI Ruidie, ZHANG Xiujun, LI Ning. Neurodevelopmental toxicity and Parkinsonism-like symptoms induced by nano-alumina exposure in zebrafish[J]. Journal of Environmental and Occupational Medicine, 2024, 41(7): 814-821. DOI: 10.11836/JEOM23424
    [2]XIA Yuan, WANG Chunyu, LI Ziyi, ZHOU Qin, ZHU Jiawei, MENG Xiaojing, HUANG Weichan, WANG Junyi, CHEN Qingsong. Effects of lead and manganese combined exposure on neurodevelopmental toxicity and JNK expression in zebrafish[J]. Journal of Environmental and Occupational Medicine, 2023, 40(5): 583-588. DOI: 10.11836/JEOM22224
    [3]LIU Yong, LIANG Jia, GUO Jiabin, PENG Hui. Research progress of model animal zebrafish in toxicity evaluation of microplastics[J]. Journal of Environmental and Occupational Medicine, 2022, 39(10): 1172-1179. DOI: 10.11836/JEOM22148
    [4]HE Mengting, WANG Wei, XU Jie, ZHANG Jie. Role of oxidative stress in neurodevelopmental toxicity of bromoacetamide in zebrafish embryos[J]. Journal of Environmental and Occupational Medicine, 2021, 38(6): 586-592. DOI: 10.13213/j.cnki.jeom.2021.20580
    [5]WANG Wei, HE Mengting, XU Jie, ZHANG Jie. Aryl hydrocarbon receptor-mediated developmental toxicity in zebrafish embryos induced by bisphenol A[J]. Journal of Environmental and Occupational Medicine, 2021, 38(4): 342-349. DOI: 10.13213/j.cnki.jeom.2021.20505
    [6]JIANG Rong-juan, ZHAO Chao-chao, WANG Cheng-qiang, SONG Jia-le, QIAN Bo. Effects of decabromodiphenyl ether exposure during pregnant and lactating periods on neurosteroid and learning and memory ability of offspring mice[J]. Journal of Environmental and Occupational Medicine, 2020, 37(9): 909-914. DOI: 10.13213/j.cnki.jeom.2020.20137
    [7]GU Jie, WANG Hong-ye, LIAO Zhen-dong, SHI Li-li, JI Gui-xiang. Neurodevelopmental toxicities of bisphenol AP and bisphenol AF in early life of zebrafish[J]. Journal of Environmental and Occupational Medicine, 2019, 36(1): 11-16. DOI: 10.13213/j.cnki.jeom.2019.18404
    [8]YAN Meng-ling , ZHOU Zhi-jun , CHANG Xiu-li . Research Progress on Neurodevelopmental Toxicity of Paraquat[J]. Journal of Environmental and Occupational Medicine, 2015, 32(3): 275-278. DOI: 10.13213/j.cnki.jeom.2015.14401
    [9]DUAN Lei , NIE Ji-sheng . Advancement in Research of Benzo[a]pyrene Toxicity on Neurodevelopment[J]. Journal of Environmental and Occupational Medicine, 2011, 28(11): 697-700.
    [10]XU Juan , WU Nan-xiang , CHEN Qiong-jiang , SONG Yang , CHEN Ru-jia . Effects of Aroclor1254 on Embryo Development,Histology and Vitellogenin Expression in Liver of Zebrafish[J]. Journal of Environmental and Occupational Medicine, 2011, 28(9): 577-581.
  • Cited by

    Periodical cited type(1)

    1. 安浩,张宴. 微塑料和三氯生对斑马鱼的神经毒性效应研究. 能源环境保护. 2023(04): 131-139 .

    Other cited types(1)

Catalog

    Article views (1575) PDF downloads (131) Cited by(2)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return