Isoliquiritigenin induces neurodevelopmental-toxicity and anxiety-like behavior in zebrafish larvae

异甘草素 斑马鱼 多巴胺能 生物 下丘脑-垂体-甲状腺轴 神经毒性 药理学 内分泌学 内科学 生理学 毒性 医学 多巴胺 生物化学 三碘甲状腺素 激素 基因
作者
Lizhen Wang,Lei Mou,Shibing Guan,Chuansen Wang,Attila Sı́k,Rostyslav Stoika,Kechun Liu,Meng Jin
出处
期刊:Comparative Biochemistry and Physiology C-toxicology & Pharmacology [Elsevier BV]
卷期号:266: 109555-109555 被引量:9
标识
DOI:10.1016/j.cbpc.2023.109555
摘要

Isoliquiritigenin, a flavonoid compound, exhibits a variety of pharmacological properties, including anti-inflammatory, anti-oxidative, anti-microbial, anti-viral, and anti-tumor effects. In the past few years, the consumption of isoliquiritigenin-containing dietary supplements has increased due to their health benefits. Although the neuroprotective effects of isoliquiritigenin have been well-investigated, these studies were performed in cells and adult animals. The potential effects of isoliquiritigenin on the development, especially the neurodevelopment, of certain populations, such as zebrafish larvae, have not been investigated. In this study, zebrafish larvae were employed as a model to investigate the effects of isoliquiritigenin on development and neurodevelopment. Zebrafish embryos treated with high concentrations of isoliquiritigenin (10 and 15 μM) exhibited high rates of mortality, hatching, and malformation, indicating that isoliquiritigenin can affect zebrafish development. In addition, isoliquiritigenin impeded the development of central nervous system regions and the length of dopaminergic neurons located in midbrains and thalami of transgenic zebrafish larvae. The locomotor ability of zebrafish larvae exposed to high concentrations of isoliquiritigenin was negatively affected. The total distance and the average velocity significantly decreased, and anxiety-related behaviors were observed under light-dark challenge. Furthermore, the levels of gap43, tuba1b, mbp, hcrt, vmat2, and pomc, which mediate neurodevelopment, neurotoxicity, and anxiety were significantly decreased in zebrafish larvae exposed to isoliquiritigenin. These results indicate that isoliquiritigenin can disrupt the development of dopaminergic neurons and the function of the central nervous system in zebrafish, causing anxiety-like symptoms.
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