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Mechanism of the Synergistic Toxicity of Ampicillin and Cefazoline on Selenastrum capricornutum

机译:氨苄西林和头孢唑啉对硒的协同毒性机制

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摘要

Ampicillin (AMP) and cefazolin (CZO) are commonly used β-lactam antibiotics which are extensively globally produced. Additionally, AMP and CZO are known to have relatively high ecotoxicity. Notably, the mix of AMP and CZO creates a synergistic effect that is more harmful to the environment, and how exposure to AMP-CZO can induce synergism in algae remains virtually unknown. To yield comprehensive mechanistic insights into chemical toxicity, including dose–response relationships and variations in species sensitivity, the integration of multiple endpoints with de novo transcriptomics analyses were used in this study. We employed Selenastrum capricornutum to investigate its toxicological responses to AMP and CZO at various biological levels, with the aim of elucidating the underlying mechanisms. Our assessment of multiple endpoints revealed a significant growth inhibition in response to AMP at the relevant concentrations. This inhibition was associated with increased levels of reactive oxygen species (ROS) and perturbations in nitrogen metabolism, carbohydrate metabolism, and energy metabolism. Growth inhibition in the presence of CZO and the AMP-CZO combination was linked to reduced viability levels, elevated ROS production, decreased total soluble protein content, inhibited photosynthesis, and disruptions in the key signaling pathways related to starch and sucrose metabolism, ribosome function, amino acid biosynthesis, and the production of secondary metabolites. It was concluded from the physiological level that the synergistic effect of Chlorophyll a (Chla) and Superoxide dismutase (SOD) activity strengthened the growth inhibition of S. capricornutum in the AMP-CZO synergistic group. According to the results of transcriptomic analysis, the simultaneous down-regulation of LHCA4, LHCA1, LHCA5, and sodA destroyed the functions of the photosynthetic system and the antioxidant system, respectively. Such information is invaluable for environmental risk assessments. The results provided critical knowledge for a better understanding of the potential ecological impacts of these antibiotics on non-target organisms.
机译:氨苄西林 (AMP) 和头孢唑啉 (CZO) 是常用的β-内酰胺类抗生素,在全球范围内广泛生产。此外,已知 AMP 和 CZO 具有相对较高的生态毒性。值得注意的是,AMP 和 CZO 的混合物会产生对环境更有害的协同效应,并且暴露于 AMP-CZO 如何在藻类中诱导协同作用仍然几乎未知。为了对化学毒性产生全面的机制见解,包括剂量-反应关系和物种敏感性的变化,本研究使用了多个终点与从头转录组学分析的整合。我们使用 Selenastrum capricornutum 研究其在不同生物学水平上对 AMP 和 CZO 的毒理学反应,以阐明其潜在机制。我们对多个终点的评估显示,相关浓度的 AMP 对生长有显著的抑制作用。这种抑制与活性氧 (ROS) 水平的增加以及氮代谢、碳水化合物代谢和能量代谢的扰动有关。在 CZO 和 AMP-CZO 组合存在下生长抑制与活力水平降低、ROS 产生增加、总可溶性蛋白含量降低、光合作用抑制以及与淀粉和蔗糖代谢、核糖体功能、氨基酸生物合成和次生代谢物产生相关的关键信号通路的破坏有关。从生理水平得出结论,叶绿素 a (Chla) 和超氧化物歧化酶 (SOD) 活性的协同作用增强了 AMP-CZO 协同组对 S. capricornutum 的生长抑制。转录组学分析结果显示,LHCA4 、 LHCA1 、 LHCA5 和 sodA 的同时下调分别破坏了光合系统和抗氧化系统的功能。这些信息对于环境风险评估非常宝贵。结果为更好地了解这些抗生素对非目标生物的潜在生态影响提供了关键知识。

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