Cannabidiol exposure during embryonic period caused serious malformation in embryos and inhibited the development of reproductive system in adult zebrafish

文献类型： 外文期刊

第一作者： Li, Lin

作者： Li, Lin;Fan, Bei;Zhang, Yifan;Zhao, Mengying;Wang, Fengzhong;Li, Minmin;Fan, Bei;Li, Minmin;Kong, Zhiqiang

作者机构：

关键词： Cannabidiol; Zebrafish; Extracellular matrix; Sight ability; Integrated stress response; Steroid homeostasis

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：8.2； 五年影响因子：8.6 ）

ISSN： 0048-9697

年卷期： 2024 年 950 卷

页码：

收录情况： SCI

摘要： Cannabidiol (CBD) is a non-psychoactive component of cannabis with potential applications in biomedicine, food, and cosmetics due to its analgesic, anti-inflammatory, and anticonvulsant properties. However, increasing reports of adverse CBD exposure events underscore the necessity of evaluating its toxicity. In this study, we investigated the developmental toxicity of CBD in zebrafish during the embryonic (0-4 dpf, days post fertilization) and early larval stages (5-7 dpf). The median lethal concentration of CBD in embryos/larvae is 793.28 mu g/L. CBD exhibited concentration-dependent manner (ranging from 250 to 1500 mu g/L) in inducing serious malformed somatotypes, like shorter body length, pericardial cysts, vitelline cysts, spinal curvature, and smaller eyes. However, no singular deformity predominates. The 5-month-old zebrafish treated with 100 and 200 mu g/L of CBD during the embryonic and early larval stages produced fewer offspring with higher natural mortality and malformation rate. Gonadal growth and gamete development were inhibited. Transcriptomic and metabolomic analyses conducted with 400 mu g/L CBD on embryos/larvae from 0 to 5 dpf suggested that CBD promoted the formation and transportation of extracellular matrix components on 1 dpf, promoting abnormal cell division and migration, probably resulting in random malformed somatotypes. It inhibited optical vesicle development and photoreceptors formation on 2 and 3 dpf, resulting in damaged sight and smaller eye size. CBD also induced an integrated stress response on 4 and 5 dpf, disrupting redox, protein, and cholesterol homeostasis, contributing to cellular damage, physiological dysfunction, embryonic death, and inhibited reproductive system and ability in adult zebrafish. At the tested concentrations, CBD exhibited developmental toxicity, lethal toxicity, and reproductive inhibition in zebrafish. These findings demonstrate that CBD threatens the model aquatic animal, highlighting the need for additional toxicological evaluations of CBD before its inclusion in dietary supplements, edible food, and other products.

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