Frontiers in Pharmacology (Aug 2022)

Cysteamine affects skeletal development and impairs motor behavior in zebrafish

  • Chao Chen,
  • Chao Chen,
  • Yongliang Zheng,
  • Yongliang Zheng,
  • Xue Li,
  • Xue Li,
  • Li Zhang,
  • Li Zhang,
  • Kangyu Liu,
  • Kangyu Liu,
  • Sujie Sun,
  • Sujie Sun,
  • Zilin Zhong,
  • Zilin Zhong,
  • Hongmei Hu,
  • Hongmei Hu,
  • Fasheng Liu,
  • Guanghua Xiong,
  • Xinjun Liao,
  • Huiqiang Lu,
  • Yanlong Bi,
  • Jianjun Chen,
  • Jianjun Chen,
  • Zigang Cao

DOI
https://doi.org/10.3389/fphar.2022.966710
Journal volume & issue
Vol. 13

Abstract

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Cysteamine is a kind of feed additive commonly used in agricultural production. It is also the only targeted agent for the treatment of cystinosis, and there are some side effects in clinical applications. However, the potential skeletal toxicity remains to be further elucidated. In this study, a zebrafish model was for the first time utilized to synthetically appraise the skeletal developmental defects induced by cysteamine. The embryos were treated with 0.35, 0.70, and 1.05 mM cysteamine from 6 h post fertilization (hpf) to 72 hpf. Substantial skeletal alterations were manifested as shortened body length, chondropenia, and abnormal somite development. The results of spontaneous tail coiling at 24 hpf and locomotion at 120 hpf revealed that cysteamine decreased behavioral abilities. Moreover, the level of oxidative stress in the skeleton ascended after cysteamine exposure. Transcriptional examination showed that cysteamine upregulated the expression of osteoclast-related genes but did not affect osteoblast-related genes expression. Additionally, cysteamine exposure caused the downregulation of the Notch signaling and activating of Notch signaling partially attenuated skeletal defects. Collectively, our study suggests that cysteamine leads to skeletal developmental defects and reduces locomotion activity. This hazard may be associated with cysteamine-mediated inhibition of the Notch signaling and disorganization of notochordal cells due to oxidative stress and apoptosis.

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