2. Academic Validation
  3. Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway

Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway

  • Ecotoxicol Environ Saf. 2024 Oct 15:285:117031. doi: 10.1016/j.ecoenv.2024.117031.
Zhengwei Huang 1,  Congcong Chen 2,  Kaiyu Guan 3,  Shengnan Xu 4,  Xiaoyu Chen 5,  Yihao Lin 5,  Xi Li 6,  Yunfeng Shan 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou, Zhejiang 325000, China; College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China.
  • 2 The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou, Zhejiang 325000, China; College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China.
  • 3 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
  • 4 The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 5 Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 6 The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou, Zhejiang 325000, China; College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China. Electronic address: xili_ihb@126.com.
  • 7 Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: shanyunfeng@wmu.edu.cn.
PMID: 39341137 DOI: 10.1016/j.ecoenv.2024.117031
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.

Keywords

6PPD-quinone; Ghrelin; Transcriptomic; Zebrafish larvae.

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