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

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 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.

Protective effect of curcumin on zebrafish liver under ethanol-induced oxidative stress.

Oxidative stress has an important role in determining severe damage to the liver, including steatosis. Curcumin (CUR) is a natural polyphenol compound with antioxidant potential but its mechanism is still unclear. In this study, 2% ethanol (ETH) was used to establish a liver injury model in Tg (fabp10: Ps Red) transgenic zebrafish with the fluorescent liver. Ethanol-treated zebrafish had an increased vacuole rate at 144 h post-fertilization (hpf), thus confirming the effectiveness of the proposed model in inducing liver damage. However, when ethanol was submitted to co-exposure with curcumin, fluorescence area and signal intensity, as well as vacuole rate, were similar to the levels found in the control group. RNA-seq results showed that ethanol and CUR affected the regulation of catalytic activity and phenylalanine metabolism, biosynthesis of amino acids, and arginine and proline metabolism signaling pathways. QRT-PCR analysis also showed that treatment with CUR led to the downregulation of genes involved in the Nrf2-Keap1 signaling pathway and altered the expression pattern of genes related to glutathione metabolism (gsr, gpx1a, gstp1, gsto1, and idh1a). CUR also induced an increase in GSH content and recovered decreased GSH caused by ethanol exposure. The findings discussed herein indicate that CUR can promote glutathione synthesis, which aided in the recovery from ethanol-induced liver damage in zebrafish larvae.