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Developmental neurotoxicity of maneb: Notochord defects, mitochondrial dysfunction and hypoactivity in zebrafish (Danio rerio) embryos and larvae.
Ecotoxicol Environ Saf 2019; 170:227-237EE

Abstract

Broad applications and exposure to the fungicide maneb can lead to toxicity in non-target organisms. Maneb is also associated with neurogenerative diseases such as Parkinson's disease (PD). The objectives of this study were to determine the acute toxicity of maneb to zebrafish by measuring mitochondrial bioenergetics, locomotor activity, and the expression of genes related to the oxidative damage response, as well as those related to dopamine signaling due to its association with PD. Zebrafish embryos at 6 h post-fertilization (hpf) were exposed to either solvent control (0.1% DMSO, v/v), or one dose of 0.1, 0.5, 1.0 and 10.0 µM maneb for 96 h. Maneb was moderately toxic to zebrafish embryos, and had a 96-h LC50 value of 4.29 μM (~ 1.14 mg/L). Maneb induced a dose-dependent increase in mortality, decreased hatching rate, and increased notochord deformity rate at both 1.0 and 10.0 µM after 72 and 96 h. Total body length was also significantly reduced with 1.0 µM maneb. A 50-60% decrease in mean basal oxygen consumption rate was also observed in embryos following a 24 hpf exposure to 10.0 µM maneb but oligomycin-induced ATP production and FCCP-induced maximum respiration remained unaffected. No change was detected in the expression levels of genes associated with oxidative stress (sod1 and sod2), nor those related to dopamine synthesis (th1), dopamine transporter (dat), dopamine receptors (drd1, drd2a, drd3, and drd4b). Thus, modifying the expression of these transcripts may not be a mechanism for maneb-induced developmental toxicity in zebrafish. To assess the potential for neurotoxicity, a dark photokinesis assay was conducted in larvae following 7 d exposure to 0.1, 0.5 and 1.0 μM maneb. Larvae exposed to 0.5 and 1.0 μM maneb showed signs related to hypoactivity, and this reduced activity is hypothesized to be associated with notochord defects as this deformity was prevalent at higher concentrations of maneb. Overall, these data demonstrate that maneb negatively affects embryonic development (i.e. notochord development), affects basal oxygen consumption rates of embryos, and induces hypoactivity in larval fish. This study improves understanding regarding the developmental neurotoxicity of the fungicide maneb to zebrafish.

Authors+Show Affiliations

Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100081, China.Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA; School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China.Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. Electronic address: cmartyn@ufl.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30529917

Citation

Cao, Fangjie, et al. "Developmental Neurotoxicity of Maneb: Notochord Defects, Mitochondrial Dysfunction and Hypoactivity in Zebrafish (Danio Rerio) Embryos and Larvae." Ecotoxicology and Environmental Safety, vol. 170, 2019, pp. 227-237.
Cao F, Souders CL, Li P, et al. Developmental neurotoxicity of maneb: Notochord defects, mitochondrial dysfunction and hypoactivity in zebrafish (Danio rerio) embryos and larvae. Ecotoxicol Environ Saf. 2019;170:227-237.
Cao, F., Souders, C. L., Li, P., Pang, S., Liang, X., Qiu, L., & Martyniuk, C. J. (2019). Developmental neurotoxicity of maneb: Notochord defects, mitochondrial dysfunction and hypoactivity in zebrafish (Danio rerio) embryos and larvae. Ecotoxicology and Environmental Safety, 170, pp. 227-237. doi:10.1016/j.ecoenv.2018.11.110.
Cao F, et al. Developmental Neurotoxicity of Maneb: Notochord Defects, Mitochondrial Dysfunction and Hypoactivity in Zebrafish (Danio Rerio) Embryos and Larvae. Ecotoxicol Environ Saf. 2019 Apr 15;170:227-237. PubMed PMID: 30529917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental neurotoxicity of maneb: Notochord defects, mitochondrial dysfunction and hypoactivity in zebrafish (Danio rerio) embryos and larvae. AU - Cao,Fangjie, AU - Souders,Christopher L,2nd AU - Li,Pengfei, AU - Pang,Sen, AU - Liang,Xuefang, AU - Qiu,Lihong, AU - Martyniuk,Christopher J, Y1 - 2018/12/06/ PY - 2018/08/06/received PY - 2018/10/14/revised PY - 2018/11/23/accepted PY - 2018/12/12/pubmed PY - 2019/3/21/medline PY - 2018/12/12/entrez KW - Developmental neurotoxicity KW - Larval behavior KW - Maneb KW - Mitochondrial bioenergetics KW - Zebrafish embryos SP - 227 EP - 237 JF - Ecotoxicology and environmental safety JO - Ecotoxicol. Environ. Saf. VL - 170 N2 - Broad applications and exposure to the fungicide maneb can lead to toxicity in non-target organisms. Maneb is also associated with neurogenerative diseases such as Parkinson's disease (PD). The objectives of this study were to determine the acute toxicity of maneb to zebrafish by measuring mitochondrial bioenergetics, locomotor activity, and the expression of genes related to the oxidative damage response, as well as those related to dopamine signaling due to its association with PD. Zebrafish embryos at 6 h post-fertilization (hpf) were exposed to either solvent control (0.1% DMSO, v/v), or one dose of 0.1, 0.5, 1.0 and 10.0 µM maneb for 96 h. Maneb was moderately toxic to zebrafish embryos, and had a 96-h LC50 value of 4.29 μM (~ 1.14 mg/L). Maneb induced a dose-dependent increase in mortality, decreased hatching rate, and increased notochord deformity rate at both 1.0 and 10.0 µM after 72 and 96 h. Total body length was also significantly reduced with 1.0 µM maneb. A 50-60% decrease in mean basal oxygen consumption rate was also observed in embryos following a 24 hpf exposure to 10.0 µM maneb but oligomycin-induced ATP production and FCCP-induced maximum respiration remained unaffected. No change was detected in the expression levels of genes associated with oxidative stress (sod1 and sod2), nor those related to dopamine synthesis (th1), dopamine transporter (dat), dopamine receptors (drd1, drd2a, drd3, and drd4b). Thus, modifying the expression of these transcripts may not be a mechanism for maneb-induced developmental toxicity in zebrafish. To assess the potential for neurotoxicity, a dark photokinesis assay was conducted in larvae following 7 d exposure to 0.1, 0.5 and 1.0 μM maneb. Larvae exposed to 0.5 and 1.0 μM maneb showed signs related to hypoactivity, and this reduced activity is hypothesized to be associated with notochord defects as this deformity was prevalent at higher concentrations of maneb. Overall, these data demonstrate that maneb negatively affects embryonic development (i.e. notochord development), affects basal oxygen consumption rates of embryos, and induces hypoactivity in larval fish. This study improves understanding regarding the developmental neurotoxicity of the fungicide maneb to zebrafish. SN - 1090-2414 UR - https://www.unboundmedicine.com/medline/citation/30529917/Developmental_neurotoxicity_of_maneb:_Notochord_defects_mitochondrial_dysfunction_and_hypoactivity_in_zebrafish__Danio_rerio__embryos_and_larvae_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0147-6513(18)31255-7 DB - PRIME DP - Unbound Medicine ER -