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Benfuresate induces developmental toxicity in zebrafish larvae by generating apoptosis and pathological modifications
Pesticide Biochemistry and Physiology ( IF 4.7 ) Pub Date : 2021-02-01 , DOI: 10.1016/j.pestbp.2020.104751
Jin-Young Lee , Hahyun Park , Whasun Lim , Gwonhwa Song

Abstract Benfuresate (2,3-dihydro-3,3-dimethylbenzofuran-5-yl ethanesulphonate) is a widely used pre-emergence herbicide of the benzofurane group, which works through the inhibition of lipid synthesis. During embryonic development of zebrafish, benfuresate retards growth while causing internal changes in the body, including alteration of the expression of cell cycle regulators, induction of apoptosis, and suppression of the circulatory system. Acute toxicity towards benfuresate is seen across the range of 5–15 μM in a dose-dependent manner and contributes to pathological conditions and subsequent morphological changes. For embryos 120 h post fertilization (hpf), benfuresate exposure results in an array of malformations involving eye or otolith development, pericardial edema, yolk sac edema, and abnormal curvature of the spine. Mechanistically, benfuresate exposure altered the transcription levels of the proliferative pathway genes ccnd1, ccne1, cdk2, and cdk6, all of which sensitize cells to apoptosis. Benfuresate exposure also affected vascular formation, including the formation of various vessels (DA, SIVs, CA, CV) whose functions in lymphatic-blood circulation were disrupted following decreased vegfaa, vegfc, flt1, flt4, and kdrl expression. These findings provide evidence of embryo-larval toxicity due to benfuresate and highlight the perils of herbicide exposure for non-target organisms far removed from application sites, especially in aquatic environments.

中文翻译:

Benfuresate 通过产生细胞凋亡和病理改变诱导斑马鱼幼虫的发育毒性

摘要 Benfuresate(2,3-二氢-3,3-二甲基苯并呋喃-5-基乙磺酸酯)是一种广泛使用的苯并呋喃类芽前除草剂,通过抑制脂质合成起作用。在斑马鱼的胚胎发育过程中,苯呋酯会阻碍生长,同时引起体内变化,包括细胞周期调节因子表达的改变、细胞凋亡的诱导和循环系统的抑制。对苯呋酯的急性毒性以剂量依赖性方式出现在 5-15 μM 的范围内,并导致病理状况和随后的形态变化。对于受精后 120 小时 (hpf) 的胚胎,苯呋酯暴露会导致一系列畸形,包括眼睛或耳石发育、心包水肿、卵黄囊水肿和脊柱异常弯曲。从机制上讲,苯呋酯暴露改变了增殖途径基因 ccnd1、ccne1、cdk2 和 cdk6 的转录水平,所有这些基因都使细胞对凋亡敏感。苯呋酯暴露还影响血管形成,包括各种血管(DA、SIV、CA、CV)的形成,其在淋巴-血液循环中的功能在 vegfaa、vegfc、flt1、flt4 和 kdrl 表达降低后受到破坏。这些发现提供了苯呋草酯引起的胚胎-幼虫毒性的证据,并强调了远离施用地点的非目标生物接触除草剂的危险,特别是在水生环境中。包括各种血管(DA、SIV、CA、CV)的形成,其在淋巴-血液循环中的功能在 vegfaa、vegfc、flt1、flt4 和 kdrl 表达降低后被破坏。这些发现提供了苯呋草酯引起的胚胎-幼虫毒性的证据,并突出了远离施用地点的非目标生物接触除草剂的危险,尤其是在水生环境中。包括各种血管(DA、SIV、CA、CV)的形成,其在淋巴-血液循环中的功能在 vegfaa、vegfc、flt1、flt4 和 kdrl 表达降低后被破坏。这些发现提供了苯呋草酯引起的胚胎-幼虫毒性的证据,并强调了远离施用地点的非目标生物接触除草剂的危险,特别是在水生环境中。
更新日期:2021-02-01
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