El Safadi Mahmoud, Shah Tawaf Ali, Zahara Syeda Sania, Bin Jardan Yousef A, Bourhia Mohammed
Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Abu Dhabi, Al Ain, United Arab Emirates.
College of Engineering and Food Sciences, Shandong University of Technology, Zibo 255000, China.
Tissue Cell. 2025 Apr;93:102733. doi: 10.1016/j.tice.2025.102733. Epub 2025 Jan 11.
Bifenthrin (BFN) is a noxious insecticide which is reported to damage various body organs. Daidzein (DZN) is a natural flavone with excellent pharmacological properties. This research was conducted to evaluate the alleviative strength of DZN to counteract BFN prompted liver toxicity in male albino rats. Thirty-two rats were divided into 4 groups i.e., the control, BFN (7 mg /kg), BFN (7 mg/kg) + DZN (20 mg/kg) and DZN (20 mg/kg) alone group. The biochemical assessment was performed by using qRT PCR as well as standard ELISA protocols. The findings are validated by applying pharmacodynamic techniques including molecular simulation. It was observed that BFN reduced the gene expressions of phosphoinositide 3-kinase (PI3K), phosphatidylinositol-3, 4, 5-triphosphate (PIP3), Protein kinase B (Akt), nuclear factor erythroid 2-related factor 2 (Nrf-2) while promoting the gene expressions of Kelch-like ECH-associated protein 1 (Keap-1). Moreover, BFN notably reduced the activities of glutathione reductase (GSR), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) while elevating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). BFN promoted the levels of matrix metallopeptidase 2 (MMP-2), Procollagen III N-terminal Pro-peptide (PIIINP), alkaline phosphatase (ALP), transforming growth factor-beta-1 (TGF-β1), aspartate aminotransferase (AST), tissue inhibitor of matrix metalloproteinases 1 (TIMP1), and alanine aminotransferase (ALT). The levels of nuclear factor- kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) were increased following the BFN intoxication. BFN enhanced the expressions of cysteine-aspartic acid protease-3 (Caspase-3) and Bcl-2-associated X protein (Bax) while suppressing the gene expression of B-cell lymphoma-2 (Bcl-2). Moreover, BFN disrupted the normal histology of liver tissues. Nonetheless, DZN treatment remarkably alleviated hepatic damages owing to its antioxidative, anti-apoptotic as well as anti-inflammatory abilities. However, DZN supplementation remarkably safeguarded which is further confirmed by in-silico assessment.
联苯菊酯（BFN）是一种有害杀虫剂，据报道会损害人体多个器官。大豆苷元（DZN）是一种具有优异药理特性的天然黄酮。本研究旨在评估DZN对雄性白化大鼠中BFN引发的肝脏毒性的缓解强度。32只大鼠被分为4组，即对照组、BFN（7毫克/千克）组、BFN（7毫克/千克）+ DZN（20毫克/千克）组和单独的DZN（20毫克/千克）组。通过定量逆转录聚合酶链反应（qRT PCR）以及标准酶联免疫吸附测定（ELISA）方案进行生化评估。研究结果通过应用包括分子模拟在内的药效学技术进行验证。观察到BFN降低了磷酸肌醇3激酶（PI3K）、磷脂酰肌醇-3,4,5-三磷酸（PIP3）、蛋白激酶B（Akt）、核因子红细胞2相关因子2（Nrf-2）的基因表达，同时促进了 Kelch样ECH相关蛋白1（Keap-1）的基因表达。此外，BFN显著降低了谷胱甘肽还原酶（GSR）、血红素加氧酶-1（HO-1）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，同时提高了活性氧（ROS）和丙二醛（MDA）的水平。BFN提高了基质金属蛋白酶2（MMP-2）、前胶原III N端前肽（PIIINP）、碱性磷酸酶（ALP）、转化生长因子-β1（TGF-β1）、天冬氨酸转氨酶（AST）、基质金属蛋白酶组织抑制剂1（TIMP1）和丙氨酸转氨酶（ALT）的水平。BFN中毒后，核因子-κB（NF-κB）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和环氧化酶-2（COX-2）的水平升高。BFN增强了半胱天冬酶-3（Caspase-3）和Bcl-2相关X蛋白（Bax）的表达，同时抑制了B细胞淋巴瘤-2（Bcl-2）的基因表达。此外，BFN破坏了肝脏组织的正常组织学结构。尽管如此，DZN治疗因其抗氧化、抗凋亡和抗炎能力而显著减轻了肝脏损伤。然而，补充DZN具有显著的保护作用，这一点通过计算机模拟评估得到进一步证实。
