Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5019, Monastir, Tunisia; Higher Institute of Biotechnology, University of Monastir, Tunisia.
Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5019, Monastir, Tunisia.
Free Radic Biol Med. 2021 Feb 20;164:154-163. doi: 10.1016/j.freeradbiomed.2020.12.451. Epub 2021 Jan 8.
Epoxiconazole is one of the most commonly used fungicides in the world. The exposition of humans to pesticides is mainly attributed to its residue in food or occupational exposure in agricultural production. Because of its lipophilic character, Epoxiconazole can accumulate in the brain Heusinkveld et al. (2013) [1]. Consequently, it is urgent to explore efficient strategies to prevent or treat Epoxiconazole-related brain damages. The use of natural molecules commonly found in our diet represents a promising avenue. Flavonoids belong to a major sub-group compounds possessing powerful antioxidant activities based on their different structural and sterical properties [2]. We choose to evaluate Myricetin, a flavonoid with a wide spectrum of pharmacological effects, for its possible protective functions against Epoxiconazole-induced toxicities. The cytotoxicity induced by this fungicide was evaluated by the cell viability, cell cycle arrest, ROS generation, antioxidant enzyme activities, and Malondialdehyde production, as previously described in Hamdi et al., 2019 [3]. The apoptosis was assessed through the evaluation of the mitochondrial transmembrane potential (ΔΨm), caspases activation, DNA fragmentation, cytoskeleton disruption, nuclear condensation, appearance of sub-G0/G1 peak (fragmentation of the nucleus) and externalization of Phosphatidylserine. This study indicates that pre-treatment of F98 cells with Myricetin during 2 h before Epoxiconazole exposure significantly increased the survival of cells, restored DNA synthesis of the S phase, abrogated the ROS generation, regulated the activities of Catalase (CAT) and Superoxide Dismutase (SOD), and reduced the MDA level. The loss of mitochondrial membrane potential, DNA fragmentation, cytoskeleton disruption, chromatin condensation, Phosphatidylserine externalization, and Caspases activation were also reduced by Myricetin. Together, these findings indicate that Myricetin is a powerful natural product able to protect cells from Epoxiconazole-induced cytotoxicity and apoptosis.
抑霉唑是世界上使用最广泛的杀菌剂之一。人类暴露于农药主要归因于其在食物中的残留或在农业生产中的职业暴露。由于其亲脂性，抑霉唑可以在大脑中积累[1]。因此，迫切需要探索有效的策略来预防或治疗抑霉唑相关的脑损伤。使用我们饮食中常见的天然分子代表了一种很有前途的方法。类黄酮属于一大类化合物，根据其不同的结构和立体性质，具有强大的抗氧化活性[2]。我们选择评估杨梅素，一种具有广泛药理作用的类黄酮，因为它可能具有针对抑霉唑诱导的毒性的保护作用。Hamdi 等人曾在 2019 年描述过，通过细胞活力、细胞周期停滞、ROS 生成、抗氧化酶活性和丙二醛产生的评估来评估该杀菌剂的细胞毒性[3]。通过评估线粒体跨膜电位（ΔΨm）、半胱天冬酶激活、DNA 片段化、细胞骨架破坏、核浓缩、出现亚 G0/G1 峰（核碎裂）和磷脂酰丝氨酸外化来评估细胞凋亡。本研究表明，在暴露于抑霉唑之前，用杨梅素预处理 F98 细胞 2 小时，可显著提高细胞存活率，恢复 S 期的 DNA 合成，阻断 ROS 生成，调节 Catalase（CAT）和 Superoxide Dismutase（SOD）的活性，并降低 MDA 水平。线粒体跨膜电位丧失、DNA 片段化、细胞骨架破坏、染色质浓缩、磷脂酰丝氨酸外化和半胱天冬酶激活也被杨梅素降低。总之，这些发现表明杨梅素是一种强大的天然产物，能够保护细胞免受抑霉唑诱导的细胞毒性和细胞凋亡。
