Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Rue Avicenne, 5000, Monastir, Tunisia.
Laboratory of Histology and Cytogenetic (Research Unit of Genetic, Genotoxicity and Childhood Illness UR12ES10), Faculty of Medicine, University of Monastir, Street Avicenne, 5019, Monastir, Tunisia.
Environ Sci Pollut Res Int. 2019 Jun;26(17):17535-17547. doi: 10.1007/s11356-019-05022-3. Epub 2019 Apr 25.
Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats 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 significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract.
环酰菌胺（EPX）是一种三唑类杀菌剂，广泛应用于农业和家庭用途。这种农药的过度使用可能会对非目标生物产生各种不良影响，包括人类。由于肝脏和肾脏是该杀菌剂的靶器官，因此可能具有肝毒性和肾毒性。因此，我们的研究旨在研究 EPX 对 Wistar 大鼠肝脏和肾脏的毒性作用。大鼠接触 EPX 的浓度分别为 8、24、40 和 56mg/kg bw（分别代表无观察到效应水平（NOEL）、NOEL 的 3 倍、NOEL 的 5 倍和 NOEL 的 7 倍），暴露 28 天可显著增强肝和肾的脂质过氧化，同时增加蛋白质氧化水平。此外，本研究的结果清楚地表明，EPX 给药以剂量依赖的方式诱导 DNA 损伤水平增加。此外，EPX 处理大鼠的肝和肾抗氧化酶（如超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽 S-转移酶（GST））的活性在 8、24 和 40mg/kg bw 的浓度下显著增加。然而，在剂量为 NOEL 的 7 倍（56mg/kg bw 的 EPX）时，CAT、GPx 和 GST 的活性降低。事实上，EPX 中毒大鼠的乙酰胆碱酯酶（AChE）活性在肝脏和肾脏中均显著低于对照组。此外，我们的结果表明，EPX 给药会破坏肝脏（天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）和乳酸脱氢酶（LDH））和肾脏（尿酸和肌酐）功能。本研究中获得的生化扰动与组织病理学变化相符。由于 EPX 治疗导致肝和肾组织的整体组织形态结构严重受损，这些结果表明 EPX 给药导致肝和肾功能明显失调。
