Related Experiment Video
Updated: Oct 4, 2025
Analysis of Oxidative Stress in Zebrafish Embryos
Published on: July 7, 2014
3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos
Fümet Duygu Üstündağ1, İsmail Ünal2, Ünsal Veli Üstündağ3
1Institute of Health Sciences, Department of Biophysics, Marmara University, Istanbul, Turkey.
Abstract:
Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and research on potential therapeutic agents for PD continues. Rotenone is a neurotoxin that can pass the blood-brain barrier and is used to generate PD models in experimental animals. Boron is a microelement necessary for neural activity in the brain. Antioxidant, non-cytotoxic, anti-genotoxic, anti-carcinogenic effects of boric acid, the salt compound of boron has been reported before. Boronic acids have been approved for treatment by FDA and are included in drug discovery studies and pyridine boronic acids are a subclass of heterocyclic boronic acids used in drug design and discovery as substituted pyridines based on crystal engineering principles. The aim of our study was to determine the effect of 3-pyridinylboronic acid in rotenone-exposed zebrafish embryos, focusing on oxidant-antioxidant parameters and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes gclm, gclc, hmox1a, nqo1, and PD related genes, brain-derived neurotrophic factor, dj1, and tnfα. Zebrafish embryos were exposed to Rotenone (10 μg/l); Low Dose 3-Pyridinylboronic acid (100 μM); High Dose 3-Pyridinylboronic acid (200 μM); Rotenone + Low Dose-3-Pyridinylboronic acid (10 μg/l + 100 μM); Rotenone + High Dose-3-Pyridinylboronic acid (10 μg/l + 200 μM) in well plates for 96 h post-fertilization (hpf). Our study showed for the first time that 3-pyridinylboronic acid, as a novel sub-class of the heterocyclic boronic acid compound, improved locomotor activities, ameliorated oxidant-antioxidant status by decreasing LPO and NO levels, and normalized the expressions of bdnf, dj1, tnf⍺ and Nrf2 target genes hmox1a and nqo1 in rotenone exposed zebrafish embryos. On the other hand, it caused the deterioration of the oxidant-antioxidant balance in the control group through increased lipid peroxidation, nitric oxide levels, and decreased antioxidant enzymes. We believe that these results should be interpreted in the context of the dose-toxicity and benefit-harm relationship of the effects of 3-pyridinylboronic.
Insights
3-pyridinylboronic acid improved zebrafish embryo motor function and normalized Parkinson's disease-related gene expression in a rotenone-induced model. However, it disrupted oxidant-antioxidant balance in control groups, highlighting a dose-dependent effect.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Parkinson's disease (PD) is a common neurodegenerative disorder with ongoing research for therapeutic agents.
- Rotenone is a neurotoxin used to create PD models in animals, and boron compounds like boric acid have shown beneficial properties.
- Pyridine boronic acids are a subclass of heterocyclic boronic acids utilized in drug discovery.
Purpose of the Study:
- To investigate the therapeutic potential of 3-pyridinylboronic acid in a rotenone-induced zebrafish embryo model of Parkinson's disease.
- To assess the effects of 3-pyridinylboronic acid on oxidant-antioxidant parameters and key gene expressions related to PD and cellular defense mechanisms.
Main Methods:
- Zebrafish embryos were exposed to rotenone (10 μg/l) alone or in combination with low (100 μM) or high (200 μM) doses of 3-pyridinylboronic acid for 96 hours post-fertilization.
- Locomotor activity was measured, and biochemical assays were performed to evaluate lipid peroxidation (LPO) and nitric oxide (NO) levels.
- Gene expression analysis was conducted for Nrf2 target genes (gclm, gclc, hmox1a, nqo1) and PD-related genes (bdnf, dj1, tnfα).
Main Results:
- 3-pyridinylboronic acid significantly improved locomotor activities in rotenone-exposed zebrafish.
- The compound ameliorated the oxidant-antioxidant imbalance caused by rotenone, decreasing LPO and NO levels.
- Gene expression of bdnf, dj1, tnfα, hmox1a, and nqo1 was normalized in rotenone-exposed embryos treated with 3-pyridinylboronic acid.
- Conversely, 3-pyridinylboronic acid impaired the oxidant-antioxidant balance in control zebrafish embryos, increasing LPO and NO and decreasing antioxidant enzymes.
Conclusions:
- 3-pyridinylboronic acid demonstrates neuroprotective effects in a rotenone-induced PD zebrafish model, improving motor function and normalizing key gene expressions.
- The study highlights a critical dose-toxicity relationship for 3-pyridinylboronic acid, as it induced an imbalance in oxidant-antioxidant status in control embryos.
- Further research is warranted to understand the precise benefit-harm relationship and optimize the therapeutic application of this novel compound.
