3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:47

Enthalten in:

Neurochemical research - 47(2022), 6 vom: 10. Juni, Seite 1553-1564

Sprache:

Englisch

Beteiligte Personen:

Üstündağ, Fümet Duygu [VerfasserIn]
Ünal, İsmail [VerfasserIn]
Üstündağ, Ünsal Veli [VerfasserIn]
Cansız, Derya [VerfasserIn]
Beler, Merih [VerfasserIn]
Karagöz, Atakan [VerfasserIn]
Kara Subaşat, Hülya [VerfasserIn]
Alturfan, A Ata [VerfasserIn]
Mega Tiber, Pınar [VerfasserIn]
Emekli-Alturfan, Ebru [VerfasserIn]

Links:

Volltext

Themen:

03L9OT429T
3-Pyridinylboronic acid
3-pyridinylboronic acid
Antioxidants
Boron
Boronic Acids
Journal Article
N9E3X5056Q
NF-E2-Related Factor 2
Neuroprotective Agents
Oxidants
Parkinson’s disease
Pyridines
Rotenone
Zebrafish embryos

Anmerkungen:

Date Completed 16.12.2022

Date Revised 16.12.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11064-022-03548-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM336752245