Epoxiconazole caused oxidative stress related DNA damage and apoptosis in PC12 rat Pheochromocytoma

• Published in: Neurotoxicology (Park Forest South) 2022-03, Vol.89, p.184-190
• Main Authors: Hamdi, Hiba, Rjiba-Touati, Karima, Ayed-Boussema, Imen, M’nassri, Assma, Chaabani, Hanen, Rich, Siwar, Abid-Essefi, Salwa
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Adrenal Gland Neoplasms - chemically induced; Animals; Antifungal agents; Apoptosis; Brain; Brain injury; Caspase-3; Cell death; Cell proliferation; Cell Survival; Condensates; Cytoskeleton; Cytotoxicity; Damage; Deoxyribonucleic acid; DNA; DNA Damage; DNA fragmentation; Epoxiconazole; Epoxy Compounds; Genotoxicity; Head injuries; Lipid peroxidation; Lipids; Lipophilic; Membrane potential; Mitochondria; Occupational exposure; Occupational health; Oxidative Stress; PC12 Cells; Peroxidation; Pesticides; Pheochromocytoma - chemically induced; Pheochromocytoma cells; Rat Pheochromocytoma PC12; Rats; Reactive Oxygen Species - metabolism; Toxicity; Triazoles
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2022.02.003

Epoxiconazole is among the most widely applied pesticides worldwide. The increased use of these products could cause toxic effects on human health which are mainly associated with its residues in food or occupational exposure in agriculture. The brain is the principal target of lipophilic compounds exposure, while the data of brain injury induced by Epoxiconazole remains unclear. The purpose of our investigation was to assess the cytotoxic and genotoxic effects of the epoxiconazole in rat Pheochromocytoma (PC 12). We found that epoxiconazole could reduce the viability and proliferation of PC12 cells, induce the DNA damage, nuclear condensation, cytoskeleton network disruption and enhance the apoptotic cell death. Intracellular biochemical assay proved that EPX induces the loss of mitochondrial membrane potential (ΔΨm) and activates caspase-3. Indeed, EPX instigated ROS generation in neuronal cells, which is accompanied by an increase of lipid peroxidation as confirmed by the high levels of MDA. Interestingly, Pre-treatment of PC12 cells with the ROS scavenger N-acetylcysteine mitigated EPX-provoked DNA fragmentation and enhancement of apoptosis. Our results demonstrate that the genotoxic and cytotoxic outcomes of EPX are mediated through a ROS-dependent pathway in PC12 cells. [Display omitted] •Epoxiconazole has a potential risk to human health by inducing cytotoxic effects.•Epoxiconazole exposure induced DNA damage and apoptosis through a caspase-dependent pathway.•Epoxiconazole exposure induced oxidative stress in PC12 cells.•N-acetylcysteine mitigates EPX-induced cytotoxic and genotoxic effects in PC12 cells.