PUBLICATION
Role of Nrf2 in the antioxidation and oxidative stress induced developmental toxicity of honokiol in zebrafish
- Authors
- Li, H., Zhang, Q., Li, W., Li, H., Bao, J., Yang, C., Wang, A., Wei, J., Chen, S., Jin, H.
- ID
- ZDB-PUB-190426-7
- Date
- 2019
- Source
- Toxicology and applied pharmacology 373: 48-61 (Journal)
- Registered Authors
- Keywords
- Antioxidation, Developmental toxicity, Honokiol microemulsion, Nrf2, Oxidative stress, Zebrafish
- MeSH Terms
-
- Gene Expression Regulation, Developmental
- Superoxide Dismutase-1/genetics
- Superoxide Dismutase-1/metabolism
- Locomotion/drug effects
- Swimming
- Dose-Response Relationship, Drug
- NF-E2-Related Factor 2/genetics
- NF-E2-Related Factor 2/metabolism*
- Lignans/toxicity*
- Oxidative Stress/drug effects*
- Animals
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Catalase/genetics
- Catalase/metabolism
- Heme Oxygenase-1/genetics
- Heme Oxygenase-1/metabolism
- Signal Transduction
- Superoxide Dismutase/genetics
- Superoxide Dismutase/metabolism
- Antioxidants/metabolism*
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Biphenyl Compounds/toxicity*
- Lethal Dose 50
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 31022495 Full text @ Tox. App. Pharmacol.
- CTD
- 31022495
Citation
Li, H., Zhang, Q., Li, W., Li, H., Bao, J., Yang, C., Wang, A., Wei, J., Chen, S., Jin, H. (2019) Role of Nrf2 in the antioxidation and oxidative stress induced developmental toxicity of honokiol in zebrafish. Toxicology and applied pharmacology. 373:48-61.
Abstract
Honokiol, the main bioactive component of Magnolia officinalis, has a variety of pharmacological actions. However, its toxicity has rarely been reported. According to previous studies performed in our laboratory, honokiol microemulsion has embryo developmental toxicity. For further exploration, Zebrafish embryos were exposed to different doses of honokiol microemulsion to record the rates of mortality, malformation, and hatching. We found that high doses of honokiol microemulsion (0.6 and 0.9 μg/mL) increased mortality, inhibited hatching, caused malformation and reduced swimming activities. The low-dose group (0.15 and 0.30 μg/mL) had decreased production of reactive oxygen species (ROS), but the high-dose group had inhibited superoxide dismutase (SOD) enzyme activity and increased ROS content. The mRNA expression of sod1, sod2, catalase(cat), and heme oxygenase 1 (ho1) was up-regulated at low doses but down-regulated at high doses. The nuclear factor E2-related factor 2 (Nrf2) mRNA expression increased at low doses but decreased at high doses. After knocking down Nrf2 in zebrafish embryos, the rates of mortality and malformation were markedly increased and the hatching rate was significantly decreased. These results suggest that honokiol has antioxidative effects at low doses but causes embryo-developmental toxicity at high doses, and the Nrf2 gene may play a pivotal role in regulating these processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping