Abstract：
4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, β-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.
摘要：
4-硝基苯酚(4-NP),作为有毒和难降解的污染物，由于其不利影响，引起了极大的关注。然而,潜在的毒性作用和机制尚不清楚.在这项研究中,繁殖，发展,研究了秀丽隐杆线虫的运动和活性氧（ROS）的产生，以评估4-NP的毒性。我们使用代谢组学来评估潜在的损伤机制。通过相关性和中介分析检查了代谢物在介导4-NP与表型之间的关系中的作用。4-NP（8ng/L和8µg/L）导致育卵大小显着减少，排卵率,生殖细胞总数,头部跳动和身体弯曲，ROS的增加。然而,子宫中的精子数量，体长和体宽减少了8µg/L。此外，36种差异代谢物富集在显著的代谢途径中，包括赖氨酸的生物合成,β-丙氨酸代谢，色氨酸代谢,戊糖磷酸途径，戊糖和葡糖醛酸酯相互转化，氨基糖和核苷酸糖代谢，淀粉和蔗糖代谢，半乳糖代谢，丙酸代谢，甘油脂代谢，和雌激素信号通路。4-NP毒性的机制是由氨基酸的扰动引起的氧化应激,通过干扰碳水化合物和脂质代谢对能量代谢产生影响，并最终影响雌激素信号通路发挥毒性作用。此外，相关性和中介分析显示甘油-3P，氨基葡萄糖-6P,氨基葡萄糖-1P,UDP-半乳糖，L-天冬氨酸,尿嘧啶是生殖的潜在标志物，葡萄糖-1,6P2是发育毒性的潜在标志物。该结果提供了对4-NP引起的毒性作用所涉及的途径的洞察,并开发了潜在的生物标志物来评估4-NP毒性。
