Related Experiment Video
Updated: Feb 7, 2026
Using Alizarin Red Staining to Detect Chemically Induced Bone Loss in Zebrafish Larvae
Published on: December 28, 2021
Fluazinam impairs oxidative phosphorylation and induces hyper/hypo-activity in a dose specific manner in zebrafish
Xiao H Wang1, Shan S Zheng2, Tao Huang2
1State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, 130117, PR China; Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, University of Florida, Gainesville, FL, 32611, USA.
Abstract:
Fluazinam is a pyridinamine fungicide that induces oxidative stress and mitochondrial damage in cells, and it has been reported to be neurotoxic. To characterize the biological effects of fluazinam, we assessed mitochondrial bioenergetics, dopamine system expression, and behavior of early life staged zebrafish (0.01 μM-0.5 μM). Fluazinam at environmentally-relevant levels did not induce sub-lethal effects in larvae, but at the LC50 (0.5 μM), fluazinam decreased basal and ATP-linked respiration significantly in embryos. As mitochondria are directly related to redox homeostasis and apoptosis, the expression of genes related to oxidative stress and apoptosis were measured. Superoxide dismutase 2 (sod2), heat stock protein 70 (hsp70), bcl2-associated X protein (bax), and caspase 9 (casp9) mRNA levels were up-regulated by 0.5 μM fluazinam. Taken together, there was evidence for mitochondrial dysfunction and oxidative damage at the highest concentration of fluazinam (0.5 μM) tested. As there are reports for fluazinam-induced neurotoxicity in dopamine synthesizing cells, transcriptional targets in the dopamine system were assessed in the zebrafish. Tyrosine hydroxylase 1 (th1) and dopamine receptor 2a (drd2a) mRNA levels were decreased by 0.5 μM fluazinam, suggesting that this fungicide may affect the dopaminergic system. To further assess the potential for fluazinam-mediated neuromodulation, the dark photokinesis response was assessed in larvae following exposure. Larvae exposed to 0.1 μM fluazinam showed hyperactivity, while larvae exposed to 0.2 and 0.3 μM showed hypo-activity. This study demonstrates that fluazinam disrupts mitochondrial bioenergetics in zebrafish, inducing an oxidative stress response, and aberrant behaviors in larvae that are dose dependent.
Insights
This study shows the fungicide fluazinam damages zebrafish mitochondria and affects their dopamine system, leading to dose-dependent behavioral changes in larvae. Fluazinam exposure disrupts cellular respiration and induces oxidative stress.
Area of Science:
- Environmental toxicology
- Cellular biology
- Neuroscience
Background:
- Fluazinam is a pyridinamine fungicide known to cause oxidative stress, mitochondrial damage, and neurotoxicity.
- Understanding the biological effects of fluazinam is crucial due to its environmental presence.
Purpose of the Study:
- To characterize the biological effects of fluazinam on zebrafish, focusing on mitochondrial bioenergetics, dopamine system expression, and behavior.
- To assess the dose-dependent impacts of fluazinam on early life-stage zebrafish.
Main Methods:
- Zebrafish embryos and larvae were exposed to varying concentrations of fluazinam (0.01–0.5 μM).
- Mitochondrial respiration, gene expression (oxidative stress, apoptosis, dopamine system), and behavioral responses (dark photokinesis) were measured.
- LC50 determination was performed.
Main Results:
- Fluazinam at the LC50 (0.5 μM) significantly decreased mitochondrial respiration (basal and ATP-linked) in zebrafish embryos.
- Exposure to 0.5 μM fluazinam upregulated oxidative stress and apoptosis-related genes (sod2, hsp70, bax, casp9) and downregulated dopamine system genes (th1, drd2a).
- Larval zebrafish exhibited hyperactivity at 0.1 μM and hypo-activity at 0.2–0.3 μM fluazinam, indicating dose-dependent behavioral alterations.
Conclusions:
- Fluazinam disrupts mitochondrial bioenergetics and induces oxidative stress in zebrafish.
- The fungicide affects the dopaminergic system and causes aberrant behaviors in zebrafish larvae in a dose-dependent manner.
- These findings highlight the potential neurotoxic and developmental risks of fluazinam exposure.
Related Concept Videos
01:02Phosphorylation
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
01:25Dose-Response Relationship: Selectivity and Specificity
03:14Oxidation Numbers
01:15Pyruvate Oxidation
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
01:21Dose Size and Dosing Frequency: Determination Methods