In Vivo Toxic Effects of 4-methoxy-5-hydroxy-canthin-6-one in Zebrafish Embryos via Copper Dyshomeostasis and Oxidative Stress

Comp Biochem Physiol C Toxicol Pharmacol. 2018 Jan;204:79-87. doi: 10.1016/j.cbpc.2017.11.014. Epub 2017 Dec 5.

Abstract

Dysfunction of copper homeostasis can lead to a host of disorders, which might be toxic sometimes. 4-Methoxy-5-hydroxy-canthin-6-one (CAN) is one of the major constituents from Picrasma quassioides and responsible for its therapeutic effects. In this work, we evaluated the toxic effect of CAN (7.5μM) on zebrafish embryos. CAN treatment decreased survival, delayed hatching time and induced malformations (loss of pigmentation, pericardial edema, as well as hematologic and neurologic abnormalities). Besides, exogenous copper supplementation rescued the pigmentation and cardiovascular defects in CAN-treated embryos. Further spectroscopic studies revealed a copper-chelating activity of CAN. Then its regulation on the expressions of copper homeostasis related genes also be analyzed. In addition, CAN lowered the total activity of SOD, elevated the ROS production and altered the oxidative related genes transcriptions, which led to oxidative stress. In conclusion, we demonstrated that CAN (7.5μM) might exert its toxic effects in zebrafish embryos by causing copper dyshomeostasis and oxidative stress. It will give insight into the risk assessment and prevention of CAN-mediated toxicity.

Keywords: 4-Methoxy-5-hydroxy-canthin-6-one; Copper homeostasis; Oxidative stress; Picrasma quassioides; Zebrafish.

MeSH terms

  • Animals
  • Copper / metabolism*
  • Embryo, Nonmammalian / drug effects*
  • Homeostasis / drug effects*
  • Indoles / toxicity*
  • Lethal Dose 50
  • Molecular Structure
  • Naphthyridines / toxicity*
  • Oxidative Stress / drug effects*
  • Zebrafish / embryology*

Substances

  • Indoles
  • Naphthyridines
  • Copper
  • 4-methoxy-5-hydroxycanthin-6-one