Neuroprotective effects of Myricetin on Epoxiconazole-induced toxicity in F98 cells

Abstract

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.

Keywords: Apoptosis; Cytoskeleton disruption; DNA fragmentation; Epoxiconazole; Myricetin; Oxidative stress.