PUBLICATION
3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos
- Authors
- Üstündağ, F.D., Ünal, İ., Üstündağ, Ü.V., Cansız, D., Beler, M., Karagöz, A., Kara Subaşat, H., Alturfan, A.A., Mega Tiber, P., Emekli-Alturfan, E.
- ID
- ZDB-PUB-220211-9
- Date
- 2022
- Source
- Neurochemical research 47(6): 1553-1564 (Journal)
- Registered Authors
- Beler, Merih, Emekli-Alturfan, Ebru, Üstündağ, Ünsal Veli
- Keywords
- 3-Pyridinylboronic acid, Parkinson’s disease, Rotenone, Zebrafish embryos
- MeSH Terms
-
- Animals
- Antioxidants/metabolism
- Antioxidants/pharmacology
- Boron/metabolism
- Boron/pharmacology
- Boronic Acids/metabolism
- Boronic Acids/pharmacology
- GA-Binding Protein Transcription Factor/metabolism
- NF-E2-Related Factor 2/metabolism
- Neuroprotective Agents*/pharmacology
- Oxidants
- Oxidative Stress
- Parkinson Disease*/metabolism
- Pyridines/pharmacology
- Rotenone/toxicity
- Zebrafish/metabolism
- PubMed
- 35142995 Full text @ Neurochem. Res.
Citation
Üstündağ, F.D., Ünal, İ., Üstündağ, Ü.V., Cansız, D., Beler, M., Karagöz, A., Kara Subaşat, H., Alturfan, A.A., Mega Tiber, P., Emekli-Alturfan, E. (2022) 3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos. Neurochemical research. 47(6):1553-1564.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping