Flavonoid quercetin (QUE) has biological activities of anti-oxidation, anti-inflammation and anti-apoptosis, however, its protective effects against avermectin (AVM) induced liver toxicity in carp remains unclear. The objective of this research is to explore the biologically potent effects of QUE in AVM-induced hepatotoxicity in carp and its underlying mechanism. Therefore, we established a liver injury model in carp induced by AVM to evaluate QUE against AVM induced liver toxicity in carp. In this investigation, AVM dosage was determined as 2.404 μg/L for both groups, and an experimentation of 30 days duration was carried out. Various methods including hematoxylin and eosin (H&E) staining, biochemical kits, real-time quantitative PCR (qRT-PCR), western blotting, TUNEL, reactive oxygen species (ROS) staining, immunofluorescence (Hoseinifar, et al.), and oil red O staining were used in this study. Results showed that the growth inhibition of carp was relieved in the QUE treatment group comparing to the AVM group. In the QUE treatment group, there was a significant decrease in the levels of ALT and AST in carp liver tissue. Additionally, the histopathological damage and lipid accumulation were alleviated compared to the AVM group. Moreover, QUE prevented AVM induced decrease in the activities of antioxidant enzymes of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH), catalase (CAT) and the accumulation of reactive oxygen species (ROS), but reduced accumulation of malondialdehyde (MDA). In addition, the mRNA levels of liver pro-inflammatory factors of tumor necrosis factor-α (TNF-α), interleukin-1β (iL-1β), interleukin-6 (iL-6), interleukin-10 (iL-10) and the protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome were significantly down-regulated in the QUE treatment group in comparison to the AVM group. We also found that QUE could affect the expression of Bcl2-associated x (Bax), B-cell lymphoma-2 (Bcl-2), cleaved-cysteinyl aspartate specific proteinase (C-Caspase3) key apoptotic proteins and TUNEL-labeled apoptotic hepatocytes by regulating SIRT1/FOXO3a signal pathway. In summary, QUE alleviated the growth inhibition, liver oxidative damage, lipid accumulation, inflammatory response, and apoptosis of carp induced by AVM. QUE is a potential protective agent against liver injury induced by AVM in carp.

中文翻译：

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农药阿维菌素引起的鲤鱼肝毒性和生长抑制：槲皮素作为膳食添加剂的改善能力和潜在机制

黄酮类槲皮素（QUE）具有抗氧化、抗炎和抗细胞凋亡等生物活性，但其对阿维菌素（AVM）引起的鲤鱼肝毒性的保护作用尚不清楚。本研究的目的是探讨 QUE 在 AVM 诱导的鲤鱼肝毒性中的生物学作用及其潜在机制。因此，我们建立了AVM引起的鲤鱼肝损伤模型，以评估QUE对AVM引起的鲤鱼肝毒性的作用。本次研究中，两组AVM剂量均确定为2.404 μg/L，并进行为期30天的实验。各种方法，包括苏木精和伊红 (H&E) 染色、生化试剂盒、实时定量 PCR (qRT-PCR)、蛋白质印迹、TUNEL、活性氧 (ROS) 染色、免疫荧光（Hoseinifar 等人）和油红本研究中使用了 O 染色。结果表明，与AVM组相比，QUE处理组对鲤鱼生长的抑制作用得到缓解。在QUE治疗组中，鲤鱼肝组织中的ALT和AST水平显着降低。此外，与AVM组相比，组织病理学损伤和脂质积累得到减轻。此外，QUE可以防止AVM引起的超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、谷胱甘肽（GSH）、过氧化氢酶（CAT）等抗氧化酶活性的下降以及活性氧（ROS）的积累，但减少丙二醛（MDA）的积累。此外，肝脏促炎因子肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (iL-1β)、白细胞介素-6 (iL-6)、白细胞介素-10 (iL-10) 的 mRNA 水平与 AVM 组相比，QUE 治疗组的 NOD 样受体蛋白 3 (NLRP3) 炎症小体的蛋白水平显着下调。我们还发现QUE可以影响Bcl2相关x（Bax）、B细胞淋巴瘤-2（Bcl-2）、裂解半胱氨酰天冬氨酸特异性蛋白酶（C-Caspase3）关键凋亡蛋白和TUNEL标记的凋亡肝细胞的表达通过调节 SIRT1/FOXO3a 信号通路。综上所述，QUE减轻了AVM引起的鲤鱼的生长抑制、肝脏氧化损伤、脂质积累、炎症反应和细胞凋亡。QUE 是鲤鱼 AVM 引起的肝损伤的潜在保护剂。