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Benfuresate induces developmental toxicity in zebrafish larvae by generating apoptosis and pathological modifications

Authors
Lee, Jin-YoungPark, HahyunLim, WhasunSong, Gwonhwa
Issue Date
2월-2021
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
Benfuresate; Zebrafish larvae; Malformation; Abnormal vascular development; Apoptosis
Citation
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, v.172
Indexed
SCIE
SCOPUS
Journal Title
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
Volume
172
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/50027
DOI
10.1016/j.pestbp.2020.104751
ISSN
0048-3575
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 mu M 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.
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