PUBLICATION
Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway
- Authors
- Huang, Z., Chen, C., Guan, K., Xu, S., Chen, X., Lin, Y., Li, X., Shan, Y.
- ID
- ZDB-PUB-240929-30
- Date
- 2024
- Source
- Ecotoxicology and environmental safety 285: 117031117031 (Journal)
- Registered Authors
- Chen, Congcong, Huang, Zhengwei, Li, Xi
- Keywords
- 6PPD-quinone, Ghrelin, Transcriptomic, Zebrafish larvae
- MeSH Terms
-
- Phenylenediamines/toxicity
- Larva*/drug effects
- Dopaminergic Neurons/drug effects
- Ghrelin*
- Water Pollutants, Chemical/toxicity
- Neurotoxicity Syndromes/etiology
- Animals
- Zebrafish*
- Receptors, Ghrelin/genetics
- PubMed
- 39341137 Full text @ Ecotoxicol. Environ. Saf.
Citation
Huang, Z., Chen, C., Guan, K., Xu, S., Chen, X., Lin, Y., Li, X., Shan, Y. (2024) Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway. Ecotoxicology and environmental safety. 285:117031117031.
Abstract
The toxicity mechanisms of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), an antioxidant derivative of 6PPD via ozone reaction commonly used in rubber and tire industries, were investigated in zebrafish larvae with concentrations ranging from 0 to 50 μg/L. Despite normal hatchability, 6PPD-Q exposure led to reduced body length and swimming distance in 120 hours post-fertilization (hpf) larvae. At the highest concentration (50 μg/L), 6PPD-Q significantly impaired dopaminergic neuron development and neurotransmitter levels, including dopamine, 5-hydroxytryptamine, and glutamate. Transcriptome profiling unveiled perturbations in growth and developmental gene expression, such as upregulation of runx2a, runx2b, and ghrl (ghrelin and obestatin prepropeptide), and downregulation of stat1b, auto1, and cidea. Notably, anamorelin, a growth hormone secretagogue receptor (GHSR) agonist, recovered the behavioral deficits induced by 6PPD-Q, implying a neuroprotective role of ghrelin possibly mediated via the ghrelin/GHSR pathway. Collectively, our findings indicate that ghrelin upregulation may counteract 6PPD-Q toxicity in zebrafish larvae, shedding light on potential therapeutic avenues for mitigating the adverse effects of this antioxidant byproduct.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping