a Laboratory of Pharmacology, Faculty of Medicine of Sfax , Sfax University , Sfax , Tunisia.
b Laboratory of Enzyme Engineering and Microbiology, National Engineering School of Sfax , Sfax University , Sfax , Tunisia.
Toxicol Mech Methods. 2018 Jan;28(1):12-22. doi: 10.1080/15376516.2017.1351507. Epub 2017 Jul 25.
This study investigated the morphological, biochemical and molecular aspects of liver injury in rats after the exposure to difenoconazole and the protective effects of quercetin against hepatotoxicity and genotoxicity induced by this fungicide. Rats were given graded doses of difenoconazole associated or not to quercetin daily for 20 days. Our results showed a significant increase in PLT (platelets) and WBC (white blood cells) in rats treated with higher doses of difenoconazole (1/38 and 1/9 of LD50). However, a significant decrease in Hb (hemoglobin) rate and RBC (red blood cells) number in rats treated with higher doses of difenoconazole (1/38 and 1/9 of LD50) was obtained. Besides, difenoconazole treatment caused an increase in hepatic enzyme activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Difenoconazole increased the levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs), and decreased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and vitamin C levels in liver tissues compared to the control group. We also noted a degradation of nucleic acids, testifying difenoconazole genotoxicity. Changes in hepatic tissues were confirmed by histological findings. Co-administration of quercetin (20 mg/kg) improved hematological and biochemical parameters and showed a significant liver protective effect by decreasing MDA levels and producing advanced oxidation protein, along with increased antioxidative enzyme activities and vitamin C levels. Results were confirmed by the improvement of histological impairments. Thus, it appears that quercetin was effective in preventing acute liver injury induced by exposure to difenoconazole.
本研究调查了大鼠暴露于联苯三唑醇后肝脏损伤的形态、生化和分子方面，以及槲皮素对该杀菌剂诱导的肝毒性和遗传毒性的保护作用。大鼠每天给予不同剂量的联苯三唑醇并联合或不联合槲皮素，共 20 天。我们的结果显示，用较高剂量联苯三唑醇（LD50 的 1/38 和 1/9）处理的大鼠血小板（PLT）和白细胞（WBC）显著增加。然而，用较高剂量联苯三唑醇（LD50 的 1/38 和 1/9）处理的大鼠血红蛋白（Hb）和红细胞（RBC）数量显著减少。此外，联苯三唑醇处理导致丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和乳酸脱氢酶（LDH）的肝酶活性增加。与对照组相比，联苯三唑醇增加了丙二醛（MDA）和高级氧化蛋白产物（AOPP）的水平，降低了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）的活性和肝脏组织中的维生素 C 水平。我们还注意到核酸的降解，证明了联苯三唑醇的遗传毒性。组织学发现证实了肝脏的变化。槲皮素（20mg/kg）的共同给药改善了血液学和生化参数，并通过降低 MDA 水平和产生高级氧化蛋白，同时增加抗氧化酶活性和维生素 C 水平，显示出显著的肝脏保护作用。结果通过组织学损伤的改善得到证实。因此，槲皮素似乎有效地预防了暴露于联苯三唑醇引起的急性肝损伤。
