PUBLICATION
Ipconazole Disrupts Mitochondrial Homeostasis and Alters GABAergic Neuronal Development in Zebrafish
- Authors
- Lee, G., Banik, A., Eum, J., Hwang, B.J., Kwon, S.H., Kee, Y.
- ID
- ZDB-PUB-230109-15
- Date
- 2022
- Source
- International Journal of Molecular Sciences 24(1): (Journal)
- Registered Authors
- Eum, Juneyong, Kee, Yun
- Keywords
- ipconazole pesticide, mitochondrial dysfunction, neurodevelopmental toxicity, oxidative stress, zebrafish
- MeSH Terms
-
- Animals
- Antioxidants/metabolism
- Embryo, Nonmammalian/metabolism
- Larva/metabolism
- Mitochondria/metabolism
- Oxidative Stress
- Pesticides*/metabolism
- Water Pollutants, Chemical*/metabolism
- Zebrafish/genetics
- PubMed
- 36613936 Full text @ Int. J. Mol. Sci.
Citation
Lee, G., Banik, A., Eum, J., Hwang, B.J., Kwon, S.H., Kee, Y. (2022) Ipconazole Disrupts Mitochondrial Homeostasis and Alters GABAergic Neuronal Development in Zebrafish. International Journal of Molecular Sciences. 24(1):.
Abstract
Ipconazole, a demethylation inhibitor of fungal ergosterol biosynthesis, is widely used in modern agriculture for foliar and seed treatment, and is authorized for use in livestock feed. Waste from ipconazole treatment enters rivers and groundwater through disposal and rain, posing potential toxicity to humans and other organisms. Its metabolites remain stable under standard hydrolysis conditions; however, their neurodevelopmental toxicity is unknown. We investigated the potential neurodevelopmental toxicity of ipconazole pesticides in zebrafish (Danio rerio). Our behavioral monitoring demonstrated that the locomotive activity of ipconazole-exposed zebrafish larvae was reduced during early development, even when morphological abnormalities were undetected. Molecular profiling demonstrated that the mitochondrial-specific antioxidants, superoxide dismutases 1 and 2, and the genes essential for mitochondrial genome maintenance and functions were specifically reduced in ipconazole-treated (0.02 μg/mL) embryos, suggesting underlying ipconazole-driven oxidative stress. Consistently, ipconazole treatment substantially reduced hsp70 expression and increased ERK1/2 phosphorylation in a dose-dependent manner. Interrupted gad1b expression confirmed that GABAergic inhibitory neurons were dysregulated at 0.02 μg/mL ipconazole, whereas glutamatergic excitatory and dopaminergic neurons remained unaffected, resulting in an uncoordinated neural network. Additionally, ipconazole-treated (2 μg/mL) embryos exhibited caspase-independent cell death. This suggests that ipconazole has the potential to alter neurodevelopment by dysregulating mitochondrial homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping