Developmental toxicity induced by chelerythrine in zebrafish embryos via activating oxidative stress and apoptosis pathways

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Nov:273:109719. doi: 10.1016/j.cbpc.2023.109719. Epub 2023 Aug 15.

Abstract

Chelerythrine (CHE), a natural benzophenanthridine alkaloid, possesses various biological and pharmacological activities, such as antimicrobial, antitumor and anti-inflammatory effects. However, its adverse side effect has not been fully elucidated. Therefore, this study was designed to investigate the developmental toxicity of CHE in zebrafish. We found that CHE could lead to a notably increase of the mortality and malformation rate, while lead to reduction of the hatching rate and body length. CHE also could affect the normal developing processes of the heart, liver and phagocytes in zebrafish. Furthermore, the reactive oxygen species (ROS) and apoptosis levels were notably increased. In addition, the mRNA expressions of genes (bax, caspase-9, p53, SOD1, KEAP1, TNF-α, STAT3 and NF-κB) were significantly increased, while the bcl2 and nrf2 were notably inhibited by CHE. These results indicated that the elevation of ROS and apoptosis were involved in the developmental toxicity induced by CHE. In conclusion, CHE exhibits a developmental toxicity in zebrafish, which helps to understand the potential toxic effect of CHE.

Keywords: Apoptosis; Chelerythrine; Developmental toxicity; Oxidative stress; Zebrafish.

MeSH terms

  • Animals
  • Apoptosis
  • Benzophenanthridines / toxicity
  • Embryo, Nonmammalian
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Zebrafish* / metabolism

Substances

  • Reactive Oxygen Species
  • chelerythrine
  • Benzophenanthridines
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2