氟苯达唑(FBZ)是一种苯并咪唑驱虫药,广泛用于通过微管蛋白结合破坏微管的形成和功能来治疗寄生虫感染。最近,它的用途已经扩展到包括抗癌应用,导致环境暴露于苯并咪唑药物的增加。然而,FBZ对水生生物神经发育的影响,特别是在水生脊椎动物中,仍然知之甚少。本研究旨在利用斑马鱼模型研究FBZ在神经发育过程中的潜在发育毒性。各种评估,包括对整体发展变化的分析,形态学异常,凋亡,基因表达改变,轴突长度测量,和电生理神经功能,被执行了。FBZ暴露导致对存活率的浓度依赖性影响,孵化率,心跳,以及发育异常的发生。值得注意的是,FBZ诱导的变化包括体长减少,头部尺寸,和眼睛大小,以及中枢神经系统凋亡细胞的检测。基因表达分析显示凋亡相关基因(p53、casp3和casp8)上调,神经分化相关基因的下调(shha,nrd,ngn1和elavl3),以及神经成熟和轴突生长相关基因的改变(gap43,mbp,和syn2a)。此外,观察到运动神经元轴突长度缩短和电生理神经功能受损。这些发现为FBZ对斑马鱼胚胎神经发育的潜在风险提供了新的见解。强调需要风险预防策略和治疗方法来解决苯并咪唑驱虫药的环境毒性。
Flubendazole (FBZ) is a benzimidazole anthelmintic drug widely used for treating parasitic infections by disrupting microtubule formation and function through tubulin binding. Recently, its use has extended to include anticancer applications, leading to increased environmental exposure to benzimidazole drugs. However, the impact of FBZ on neural development in aquatic organisms, particularly in aquatic vertebrates, remains poorly understood. This study aimed to investigate the potential developmental toxicity of FBZ during neural development using zebrafish model. Various assessments, including analysis of overall developmental changes, morphological abnormalities, apoptosis, gene expression alterations, axon length measurements, and electrophysiological neural function, were performed. FBZ exposure resulted in concentration-dependent effects on survival rate, hatching rate, heartbeat, and the occurrence of developmental abnormalities. Notably, FBZ-induced changes included reductions in body length, head size, and eye size, as well as the detection of apoptotic cells in the central nervous system. Gene expression analysis revealed upregulation of apoptosis-related genes (p53, casp3, and casp8), downregulation of neural differentiation-related genes (shha, nrd, ngn1, and elavl3), and alterations in neural maturation and axon growth-related genes (gap43, mbp, and syn2a). Additionally, shortened motor neuron axon length and impaired electrophysiological neural function were observed. These findings provide novel insights into the potential risks of FBZ on the neural development of zebrafish embryos, emphasizing the need for risk prevention strategies and therapeutic approaches to address the environmental toxicity of benzimidazole anthelmintics.