Hinokitiol induces developmental and cardiovascular toxicity in zebrafish larvae and potential mechanisms

Abstract

Hinokitiol is a natural compound collected from the trunk of cypress, belonging to the tropolone family of compounds. It has anti-inflammatory, anti-tumour and antibacterial activities, making it a natural product with a wide range of applications. It is used as an additive in hair growth agents, toothpaste, make-up and furniture wood. However, the toxicity of hinokitiol remains poorly understood. Therefore, the cardiovascular and developmental toxicity of hinokitiol in organisms was investigated in zebrafish larvae. In the study, zebrafish embryos were exposed to hinokitiol for 3 days to study the developmental and cardiovascular toxicity of hinokitiol. Concentrations for the hinokitiol toxicity test were set at 0, 0.4, 0.8, 1.2, 1.6, 2.0 and 2.2 mg/L. The experimental concentrations of 0, 0.8, 1.2 and 1.6 mg/L were subsequently determined based on phenotype. The results showed that exposure to hinokitiol resulted in increased mortality, changes in hatching rates and abnormalities in the apparent morphology of zebrafish embryos/larvae (shortened body length, reduced eye area, pericardial edema, and abnormal heart rate). In addition, hinokitiol impaired the cardiovascular system of zebrafish larvae, as evidenced by the absence of morphological features of the atria and ventricles, linearization of the heart, and reduction in the area and abundance of blood vessels. In addition, hinokitiol affects mitochondrial function by affecting iron ion levels and generates oxidative stress leading to apoptosis and which then generates cardiovascular toxicity. Our findings suggest that hinokitiol causes mitochondrial dysfunction and oxidative stress through iron chelation, which in turn triggers apoptosis, ultimately leading to cardiovascular and developmental toxicity in zebrafish larvae. The study provides new insights into the safety of hinokitiol and natural products.