Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Lihua Yang; Tao Huang; Ruiwen Li; Christopher L Souders 2nd; Spencer Rheingold; Claire Tischuk; Na Li; Bingsheng Zhou; Christopher J Martyniuk

doi:10.1016/j.envpol.2020.116277

Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Environ Pollut. 2021 Feb 1:270:116277. doi: 10.1016/j.envpol.2020.116277. Epub 2020 Dec 11.

Authors

Lihua Yang¹, Tao Huang², Ruiwen Li³, Christopher L Souders 2nd⁴, Spencer Rheingold⁴, Claire Tischuk⁴, Na Li⁵, Bingsheng Zhou⁶, Christopher J Martyniuk⁷

Affiliations

¹ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, PR 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.
² 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 Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, 130117, PR China.
³ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, PR China; Ecological Environment Monitoring and Scientific Research Center, Changjiang River Basin Ecological Environment Administration, Ministry of Ecology and Environment, Wuhan, 430014, PR China.
⁴ 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.
⁵ Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 10085, PR China.
⁶ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, PR China.
⁷ 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.

PMID: 33360065
DOI: 10.1016/j.envpol.2020.116277

Abstract

Strobilurin fungicides have been frequently detected in aquatic environments and can induce mitochondrial toxicity to non-target aquatic organisms. However, the derived toxicity and subsequent mechanisms related to their adverse effects are not fully elucidated. In the present study, we compared the mitochondrial and developmental toxicity of azoxystrobin, pyraclostrobin, and trifloxystrobin using zebrafish embryo/larvae. The results showed that all three strobilurins inhibited mitochondrial and non-mitochondrial respiration (the potency is pyraclostrobin ≈ trifloxystrobin > azoxystrobin). Behavioral changes indicated that sublethal doses of pyraclostrobin and azoxystrobin caused hyperactivity of zebrafish larvae in dark cycles, whereas trifloxystrobin resulted in hypoactivity of zebrafish larvae. In addition, pyraclostrobin exposure impaired the inflation of swim bladder, and caused down-regulation of annexin A5 (anxa5) mRNA levels, and up-regulated transcript levels of pre-B-cell leukemia homeobox 1a (pbx1a); conversely, azoxystrobin and trifloxystrobin did not cause detectable effects with swim bladder inflation. Molecular docking results indicated that azoxystrobin had higher interacting potency with iodotyrosine deiodinase (IYD), prolactin receptor (PRLR), antagonistic conformation of thyroid hormone receptor β (TRβ) and glucocorticoid receptor (GR) compared to pyraclostrobin and trifloxystrobin; pyraclostrobin and azoxystrobin were more likely to interact with the antagonistic conformation of TRβ and GR, respectively. These results may partially explain the different effects observed in behavior and swim bladder inflation, and also point to potential endocrine disruption induced by these strobilurins. Taken together, our study revealed that all three strobilurins alter mitochondrial bioenergetics and cause developmental toxicity. However, the toxic phenotypes and underlying mechanisms of each chemical may differ, and this requires further investigation. Pyraclostrobin showed higher mitochondrial toxicity at lethal doses and higher developmental toxicity at sublethal doses compared to the two other strobilurins tested. These results provide novel information for toxicological study as well as risk assessment of strobilurin fungicides.

Keywords: Behavioral changes; Mitochondrial bioenergetics; Strobilurin; Swim bladder inflation; Zebrafish embryo/larvae.

MeSH terms

Animals
Fungicides, Industrial* / toxicity
Larva
Molecular Docking Simulation
Strobilurins / toxicity
Zebrafish*

Substances

Fungicides, Industrial
Strobilurins