PUBLICATION
Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and locomotor behavior in larval zebrafish (Danio rerio)
- Authors
- Zhang, J.L., Laurence Souders, C., Denslow, N.D., Martyniuk, C.J.
- ID
- ZDB-PUB-170430-7
- Date
- 2017
- Source
- Toxicology and applied pharmacology 327: 30-38 (Journal)
- Registered Authors
- Keywords
- Gene expression, Locomotor behavior, Mitocondrial respiration, Myosin, Quercetin
- MeSH Terms
-
- Abnormalities, Drug-Induced/pathology
- Adenosine Triphosphate/biosynthesis
- Animals
- Behavior, Animal/drug effects
- Dietary Supplements/toxicity*
- Energy Metabolism/drug effects*
- Female
- Larva
- Locomotion/drug effects*
- Male
- Mitochondria/drug effects*
- Mitochondria/metabolism*
- Muscle Development/drug effects
- Muscle Development/genetics
- MyoD Protein/biosynthesis
- MyoD Protein/genetics
- Oxidative Stress/drug effects
- Oxygen Consumption/drug effects
- Quercetin/toxicity*
- Swimming
- Transcription, Genetic/drug effects
- Water Pollutants, Chemical
- Zebrafish
- PubMed
- 28450151 Full text @ Tox. App. Pharmacol.
- CTD
- 28450151
Citation
Zhang, J.L., Laurence Souders, C., Denslow, N.D., Martyniuk, C.J. (2017) Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and locomotor behavior in larval zebrafish (Danio rerio). Toxicology and applied pharmacology. 327:30-38.
Abstract
Quercetin is a natural product that is sold as a supplement in health food stores. While there are reported benefits for this flavonoid as a dietary supplement due to antioxidant properties, the full scope of its biological interactions is not fully addressed. To learn more about the mechanisms of action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and 10μg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to 10μg/L did not induce significant mortality in developing fish, but did increase prevalence of an upward-curved dorsal plane in hatched larvae. To determine whether this developmental defect was potentially related to mitochondrial bioenergetics during development, we measured oxygen consumption rate in whole embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP-linked respiration were decreased at 1 and 10μg/L quercetin, and maximal respiration was decreased at 10μg/L quercetin, suggesting that quercetin impairs mitochondrial bioenergetics. This is proposed to be related to the deformities observed during development. Due to the fact that ATP production was affected by quercetin, larval behaviors related to locomotion were investigated, as well as transcriptional responses of six myogenesis transcripts. Quercetin at 10μg/L significantly reduced the swimming velocity of zebrafish larvae. The expression levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also altered by quercetin. Mstna, an inhibitory factor for myogenesis, was significantly increased at 1μg/L quercetin exposure, while myoD, a stimulatory factor for myogenesis, was significantly increased at 10μg/L quercetin exposure. There were no changes in transcripts related to apoptosis (bcl2, bax, casp3, casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish exposed to each dose, supporting an oxidative stress response. Our data support the hypothesis that quercetin may affect locomotion and induce deformities in zebrafish larvae by diminishing ATP production and by altering the expression of transcripts related to muscle formation and activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping