PUBLICATION

Cardiotoxicity of (-)-borneol, (+)-borneol, and isoborneol in Zebrafish embryos is associated with Na+ /K+ -ATPase and Ca2+ -ATPase inhibition

Authors
Ni, X., Yin, X., Qi, C., Liu, C., Chen, H., Zhou, Y., Ao, W., Bao, S., Xue, J., Yang, J., Dong, W.
ID
ZDB-PUB-220907-11
Date
2022
Source
Journal of applied toxicology : JAT   43(3): 373-386 (Journal)
Registered Authors
Dong, Wu
Keywords
Borneol, Ca+-ATPase, Heart rate, Na+/K+-ATPase, Zebrafish embryo
MeSH Terms
  • Animals
  • Camphanes/toxicity
  • Cardiotoxicity*
  • Sodium-Potassium-Exchanging ATPase/genetics
  • Sodium-Potassium-Exchanging ATPase/metabolism
  • Zebrafish*/metabolism
PubMed
36062847 Full text @ J. Appl. Toxicol.
Abstract
Borneol is an example of traditional Chinese medicine widely used in Asia. There are different isomers of chiral borneol in the market, but its toxicity and effects need further study. In this study, we used zebrafish embryos to examine the effects of exposure to three isomers of borneol [(-)-borneol, (+)-borneol, and isoborneol] on heart development and the association with Na+ /K+ -ATPase from 4 hours post-fertilization (4 hpf). The results showed that the three isomers of borneol increased mortality and decreased hatching rate when the zebrafish embryo developed to 72 hpf. All three isomers of borneol (0.01-1.0 mM) significantly reduced heart rate from 48 hpf to 120 hpf and reduced the expression of genes related to Ca2+ -ATPase (cacna1ab and cacna1da) and Na+ /K+ -ATPase (atp1b2b, atp1a3b, and atp1a2). At the same time, the three isomers of borneol significantly reduced the activities of Ca2+ -ATPase and Na+ /K+ -ATPase at 0.1 to 1.0 mM. (+)-Borneol caused the most significant reduction (p < 0.05), followed by isoborneol and (-)-borneol. Na+ /K+ -ATPase was mainly expressed in otic vesicles and protonephridium. All three isomers of borneol reduced Na+ /K+ -ATPase mRNA expression, but isoborneol was the most significant (p < 0.01). Our results indicated that (+)-borneol was the least toxic of the three isomers while the isoborneol showed the most substantial toxic effect, closely related to effects on Na+ /K+ -ATPase.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping