Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Comp Biochem Physiol C Toxicol Pharmacol. 2023 Nov;273:109722. doi: 10.1016/j.cbpc.2023.109722. Epub 2023 Aug 18.
The dinitroaniline herbicide benfluralin is used weed control in conventional systems and poses a high risk of accumulation in aquatic systems. Previous studies have shown the toxic effects of benfluralin on non-target organisms; however, its developmental toxicity in vertebrates has not yet been reported. This study demonstrated the developmental toxicity of benfluralin and its mechanism of action, using zebrafish as an aquatic vertebrate model. Benfluralin induces morphological and physiological alterations in body length, yolk sac, and heart edema. We also demonstrated a reactive oxygen species (ROS) increase of approximately 325.53 % compared with the control group after 20 μM benfluralin-treatment. In addition, the malformation of the heart and vascular structures was identified using transgenic flk1:eGFP zebrafish models at 20 μM concentration benfluralin exposure. Moreover, benfluralin induced small livers, approximately 59.81 % of normal liver size, via abnormal development of the liver as observed in the transgenic L-fabp:dsRed zebrafish. Benfluralin also inhibits normal growth via abnormal expression of cell cycle regulatory genes and increases oxidative stress, inflammation, and apoptosis. Collectively, we elucidated the mechanisms associated with benfluralin toxicity, which lead to various abnormalities and developmental toxicities in zebrafish. Therefore, this study provides information on the parameters used to assess developmental toxicity in other aquatic organisms, such as herbicides, pesticides, and environmental contaminants.
二硝基苯胺类除草剂苯氟隆被用于常规系统中的杂草控制，并且在水生系统中具有很高的积累风险。先前的研究表明苯氟隆对非靶标生物具有毒性作用；然而，其对脊椎动物的发育毒性尚未见报道。本研究以斑马鱼为水生脊椎动物模型，证明了苯氟隆的发育毒性及其作用机制。苯氟隆诱导体长、卵黄囊和心脏水肿的形态和生理改变。我们还证明了与对照组相比，在 20 μM 苯氟隆处理后，活性氧（ROS）增加了约 325.53%。此外，在 20 μM 浓度的苯氟隆暴露下，使用转基因 flk1:eGFP 斑马鱼模型鉴定出心脏和血管结构的畸形。此外，苯氟隆通过在转基因 L-fabp:dsRed 斑马鱼中观察到的肝脏异常发育，导致小肝脏，约为正常肝脏大小的 59.81%。苯氟隆还通过异常表达细胞周期调节基因、增加氧化应激、炎症和细胞凋亡来抑制正常生长。总之，我们阐明了与苯氟隆毒性相关的机制，这些机制导致了斑马鱼的各种异常和发育毒性。因此，本研究为评估其他水生生物（如除草剂、农药和环境污染物）的发育毒性提供了相关参数信息。
