Cardiotoxicity of (−)‐borneol, (+)‐borneol, and isoborneol in zebrafish embryos is associated with Na+/K+‐ATPase and Ca2+‐ATPase inhibition. Issue 3 (13th September 2022)

• Record Type: Journal Article
• Authors: Ni, Xuan; Yin, Xiaoyu; Qi, Chelimuge; Liu, Chunyu; Chen, Hao; Zhou, Yini; Ao, Wuliji; Bao, Shuyin; Xue, Jiangdong; Yang, Jingfeng; Dong, Wu
• Is Part Of: Journal of applied toxicology. Volume 43:Issue 3(2023)
• Page Start: 373
• Page End: 386
• Publication Date: 2022-09-13
• Subjects: borneol -- Ca+‐ATPase -- heart rate -- Na+/K+‐ATPase -- zebrafish embryo; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4388
• Languages: English
• ISSNs: 0260-437X

Abstract

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 h 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 to 120 hpf and reduced the expression of genes related to Ca 2+ ‐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 Ca 2+ ‐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. Abstract : This study used zebrafish embryos as an animal model to examine the effects of three borneol isomers [(−)‐borneol, (+)‐borneol, and isoborneol] on cardiac development. The results showed that all three isomers caused a decrease in heart rate, which may be related to the reduction of Na + /K + ‐ATPase and Ca 2+ ‐ATPase activities and decreased gene expression levels by borneol. The experimental results demonstrated that the toxicity caused by isoborneol was the largest, while the toxicity caused by (+)‐borneol was the least.