Environmental Safety Group, KIST Europe Forschungsgesellschaft mbH, Saarbrücken 66123, Germany; Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Biologische Experimentalphysik, Saarland University, Saarbrücken, Germany.
Ecotoxicol Environ Saf. 2024 Aug;281:116606. doi: 10.1016/j.ecoenv.2024.116606. Epub 2024 Jun 18.
Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.
非那雄胺是一种甾体 5α-还原酶抑制剂，常用于治疗良性前列腺增生和脱发。然而，尽管它被持续使用，但对其环境影响尚未进行彻底研究。因此，我们研究了非那雄胺对大型溞（一种在淡水生态系统中至关重要的浮游甲壳类动物，被选为了解生态毒理学效应的生物指示剂）的急性和慢性不良影响。慢性暴露（23 天）会对其发育和繁殖产生负面影响，导致繁殖力降低、第一胎产卵延迟、生长减缓以及幼体体积减小。此外，急性暴露（<24 小时）会导致与生殖和发育相关的关键基因表达水平降低，特别是 EcR-A/B（蜕皮激素受体）、Jhe（保幼激素酯酶）和 Vtg2（卵黄蛋白原），同时还会引起与氧化应激相关的基因表达水平降低。非靶向脂质组学/代谢组学分析揭示了脂质组的改变，包括 19 个上调和 4 个下调的富含脂质本体论类别，并证实了代谢物的下调。通路分析表明，该药物对戊糖磷酸途径、组氨酸代谢、β-丙氨酸代谢以及丙氨酸、天冬氨酸和谷氨酸代谢等代谢途径有显著影响。这项综合研究揭示了大型溞对非那雄胺暴露的复杂分子和代谢反应，强调了这种抗雄激素化合物对淡水生态系统关键物种的多方面影响。这些发现强调了理解广泛使用的药物对水生生态系统生物多样性的环境影响的重要性。
