Epoxiconazole profoundly alters rat brain and properties of neural stem cells. (February 2022)

• Record Type: Journal Article
• Authors: Hamdi, Hiba; Graiet, Imen; Abid-Essefi, Salwa; Eyer, Joel
• Is Part Of: Chemosphere. Volume 288:Part 3(2022)
• Publication Date: 2022-02
• Subjects: Pesticide -- Neural stem cells -- Oxidative stress -- DNA damage -- Mitochondria -- Cytoskeleton; bw body weight -- CAT Catalase -- EPX Epoxiconazole -- GPx Glutathion Peroxidase -- GST Glutathion S Transferase -- SOD Superoxide Dismutase -- MDA Malondialdheyde -- MMP Mitochondrial Membrane Potential -- NOEL No Observed Effect Level -- NSCs Neural Stem Cells -- PC Protein carbonyls -- ROS Reactive Oxygen Species -- SVZ Sub-ventricular Zone -- NAC N-acetylcysteine -- Rh-123 Rhodamine 123; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2021.132640
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Epoxiconazole (EPX), a widely used fungicide for domestic, medical, and industrial applications, could cause neurodegenerative diseases. However, the underling mechanism of neurotoxicity is not well understood. This study aimed to investigate the possible toxic outcomes of Epoxiconzole, a triazole fungicide, on the brain of adult rats in vivo, and in vitro on neural stem cells derived from the subventricular zone of newborn Wistar rats. Our results revealed that oral exposure to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing respectively NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days caused a considerable generation of oxidative stress in adult rat brain tissue. Furthermore, a significant augmentation in lipid peroxidation and protein oxidation has been found. Moreover, it induced an elevation of DNA fragmentation as assessed by the Comet assay. Indeed, EPX administration impaired activities of antioxidant enzymes and inhibited AChE activity. Concomitantly, this pesticide produced histological alterations in the brain of adult rats. Regarding the embryonic neural stem cells, we demonstrated that the treatment by EPX reduced the viability of cells with an IC50 of 10 μM. It also provoked the reduction of cell proliferation, and EPX triggered arrest in G1/S phase. The neurosphere formation and self-renewal capacity was reduced and associated with decreased differentiation. Moreover, EPX induced cytoskeleton disruption as evidenced by immunocytochemical analysis. Our findings also showed that EPX induced apoptosis as evidenced by a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspase-3. In addition, EPX promoted ROS production in neural stem cells. Interestingly, the pretreatment of neural stem cells with the N-acetylcysteine (ROS scavenger) attenuated EPX-induced cell death, disruption of neural stem cells properties, ROS generation and apoptosis. Thus, the use of this hazardous material should be restricted and carefully regulated. Graphical abstract: Image 1 Highlights: Epoxiconazole (EPX) induces neurotoxic effects on adult male Wistar rats. EPX induces biochemical, histopathological and cerebral oxidative stress damage. EPX affects the antioxidant system and inhibits acetylcholinesterase activity. EPX alters the properties of neural stem cells. EPX provokes oxidative stress and induces apoptosis in neural stem cells.