Study on the toxicity and action mechanism of diquat on Caenorhabditis elegans

Diquat (DQ), a contact herbicide extensively utilized in both agricultural and non-agricultural domains, exhibits a high correlation with neuronal disorders. Nevertheless, the toxicity and underlying mechanisms associated with exposure to environmental concentrations of DQ remain ambiguous. Here, we report a dose-dependent cellular neurotoxicity of DQ in C. elegans. Firstly, DQ significantly compromised the development and brood size of worms, shortened the lifespan, and caused epidermal abnormalities. An unbiased transcriptomic analysis disclosed several pathways related to cell death and peroxisome homeostasis underlying this organismal-level toxicity. Moreover, the exposure of DQ to C. elegans led to a notable increase of embryonic cell death. Concurrently, DQ exposure specifically caused the loss of dopamine neurons but not two types of neurons in adulthood, which is in accordance with DQ-induced muscle-related defects such as pharyngeal pumping, body bends, and head thrashes. Wild-type N2 Caenorhabditis elegans were exposed to 0 and 100.00 μg/L DQ dibromide monohydrate solution (Tanmo Quality Inspection Technology Co., Jiangsu, China) at a constant temperature of 20°C for 72 hours. Samples were collected for transcriptional level analysis, with the untreated 0 μg/L DQ-exposed C. elegans used as the control. In the document, control-1, control-2, and control-3 represent the three replicates for the 0 μg/L DQ treatment, while treatment-1, treatment-2, and treatment-3 represent the three replicates for the 100.00 μg/L DQ treatment.

敌草快（Diquat, DQ）是一种广泛应用于农业与非农业领域的触杀型除草剂，其与神经功能紊乱存在显著关联。然而，环境暴露浓度下的敌草快所引发的毒性及其潜在作用机制仍未明确。本研究报道了敌草快在秀丽隐杆线虫（Caenorhabditis elegans, C. elegans）中引发的剂量依赖性细胞神经毒性。首先，敌草快可显著损害线虫的生长发育与产卵量，缩短其寿命，并引发表皮形态异常。通过无偏转录组分析（unbiased transcriptomic analysis），本研究揭示了与细胞死亡及过氧化物酶体稳态（peroxisome homeostasis）相关的多条通路，作为该个体水平毒性的潜在分子机制。此外，敌草快暴露可显著提升秀丽隐杆线虫的胚胎细胞死亡比例。同时，敌草快暴露会特异性造成成年线虫多巴胺能神经元（dopamine neurons）的丢失，却不会影响另外两类神经元；该现象与敌草快引发的肌肉相关运动缺陷（如咽泵运动、身体弯曲及头部摆动异常）相一致。本研究将野生型N2株秀丽隐杆线虫置于20℃恒温环境中，分别暴露于0 μg/L与100.00 μg/L的一水合二溴敌草快（DQ dibromide monohydrate）溶液中，处理时长为72小时，实验试剂购自中国江苏天茂检测科技有限公司。随后收集样本进行转录水平分析，以未暴露敌草快的0 μg/L处理组秀丽隐杆线虫作为空白对照。本研究中，control-1、control-2与control-3代表0 μg/L敌草快处理组的三个生物学重复样本，treatment-1、treatment-2与treatment-3则代表100.00 μg/L敌草快处理组的三个生物学重复样本。