Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, Abu Dhabi, United Arab Emirates.
Department of Zoology, Division of Sciences and Technology, University of Education Township Lahore, Pakistan.
Pestic Biochem Physiol. 2024 Nov;205:106117. doi: 10.1016/j.pestbp.2024.106117. Epub 2024 Sep 4.
Abamectin (ABN) is an agricultural insecticide that is reported to damage various body organs including the heart. Velutin (VLN) is a plant-derived flavonoid that exhibits a wide range of medicinal properties. This study was planned to investigate the medicinal value of VLN against ABN induced cardiotoxicity in rats. Thirty-two male albino rats (Rattus norvegicus) were divided into four equal groups including the control, ABN (10 mg/kg), ABN (10 mg/kg) + VLN (20 mg/kg), and VLN (20 mg/kg) alone administrated group. The doses were administrated for 6 weeks orally. The results demonstrated that ABN intoxication promoted the gene expression of Nrf-2 and its associated antioxidant genes including glutathione reductase (GSR), heme‑oxygenase-1 (HO-1), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) while reducing the gene expression of Keap-1 as well as levels of ROS and MDA. Moreover, ABN exposure enhanced the gene expression of Janus kinase-1 (JAK1), Signal transducer and activator of transcription-3 (STAT3), NF-κB, TNF-α, C-reactive proteins, Interferon-gamma-induced protein 10 (IP-10), IL-1β, Monocyte chemoattractant protein-1 (MCP-1), IL-6 and COX-2. The concentrations of CK-MB, Brain natriuretic peptide (BNP), CPK, troponin-I, N-terminal pro b-type natriuretic peptide (NT-proBNP) and LDH were elevated after ABN administration. ABN intoxication abruptly upregulated the levels of Caspase-3, Caspase-9 and Bax while reducing the levels of Bcl-2 in cardiac tissues. Additionally, ABN exposure prompted various histopathological damages. Nevertheless, VLN treatment remarkably protected the cardiac tissues via regulating aforementioned disruptions. Lastly, molecular docking analysis was performed to determine the potential affinity of VLN and targeted protein i.e., Bax, NF-kB, Nrf-2/Keap1, JAK1 and STAT3. Our in-silico evaluation showed a strong binding affinitybetween VLN and the targeted proteins which further confirms its effectiveness as a cardioprotective agent.
阿维菌素（ABN）是一种农业杀虫剂，据报道它会损害包括心脏在内的各种身体器官。白杨素（VLN）是一种植物衍生的类黄酮，具有广泛的药用特性。本研究旨在探讨 VLN 对 ABN 诱导的大鼠心脏毒性的药用价值。32 只雄性白化大鼠（Rattus norvegicus）被分为四组，包括对照组、ABN（10mg/kg）组、ABN（10mg/kg）+VLN（20mg/kg）组和单独给予 VLN（20mg/kg）组。这些剂量通过口服给药 6 周。结果表明，ABN 中毒促进了 Nrf-2 及其相关抗氧化基因的表达，包括谷胱甘肽还原酶（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），同时降低了 Keap-1 基因的表达以及 ROS 和 MDA 的水平。此外，ABN 暴露增强了 Janus 激酶-1（JAK1）、信号转导和转录激活因子 3（STAT3）、NF-κB、TNF-α、C 反应蛋白、干扰素-γ诱导蛋白 10（IP-10）、IL-1β、单核细胞趋化蛋白-1（MCP-1）、IL-6 和 COX-2 的基因表达。CK-MB、脑钠肽（BNP）、CPK、肌钙蛋白-I、N 末端 pro b 型利钠肽（NT-proBNP）和 LDH 的浓度在 ABN 给药后升高。ABN 中毒会突然上调心脏组织中 Caspase-3、Caspase-9 和 Bax 的水平，同时降低 Bcl-2 的水平。此外，ABN 暴露会引起各种组织病理学损伤。然而，VLN 治疗通过调节上述干扰显著保护了心脏组织。最后，进行了分子对接分析以确定 VLN 和靶向蛋白（即 Bax、NF-kB、Nrf-2/Keap1、JAK1 和 STAT3）的潜在亲和力。我们的计算机评估显示，VLN 与靶向蛋白之间具有很强的结合亲和力，进一步证实了其作为心脏保护剂的有效性。
