Hassan Hesham M, El Safadi Mahmoud, Hayat Muhammad Faisal, Al-Emam Ahmed
Department of pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, Abu Dhabi , United Arab Emirates.
Int J Biochem Cell Biol. 2025 Feb;179:106716. doi: 10.1016/j.biocel.2024.106716. Epub 2024 Dec 5.
Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits a wide range of medicinal properties. The current trial was conducted to evaluate the ameliorative potential of SAP against FEN instigated liver toxicity in rats. Thirty-two male albino rats were apportioned into four groups including control, FEN (10 mg/kg), FEN (10 mg/kg) + SAP (80 mg/kg), and SAP (80 mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while reducing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were decreased after FEN exposure. Furthermore, FEN administration notably escalated the levels of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the levels of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while reducing the levels of Bcl-2. Hepatic histology was impaired after FEN intoxication. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our in-silico analysis confirmed that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.
杀螟硫磷（FEN）是一种有机磷杀虫剂，被认为是器官毒性的主要来源。皂草苷（SAP）是一种天然存在的新型黄酮，具有广泛的药用特性。进行当前试验以评估SAP对FEN诱发的大鼠肝脏毒性的改善潜力。将32只雄性白化大鼠分为四组，包括对照组、FEN（10毫克/千克）组、FEN（10毫克/千克）+ SAP（80毫克/千克）组和单独的SAP（80毫克/千克）治疗组。结果显示，给予FEN上调了TNF-α、TLR4、IL-1β、MYD88、IL-6、TRAF6、COX-2、NF-κB、JAK1和STAT3的基因表达，同时降低了IκB的基因表达。此外，FEN暴露后活性氧（ROS）和丙二醛（MDA）水平升高，而过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）、血红素加氧酶-1（HO-1）和谷胱甘肽还原酶（GSR）的活性降低。此外，给予FEN显著升高了包括丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、γ-谷氨酰转移酶（GGT）和碱性磷酸酶（ALP）在内的肝酶水平，而降低了总蛋白和白蛋白水平。此外，摄入FEN上调了Caspase-9、Bax和Caspase-3的水平，同时降低了Bcl-2的水平。FEN中毒后肝脏组织学受损。然而，SAP治疗通过调节上述异常情况显著保护了肝脏的正常状态。我们的计算机模拟分析证实，SAP具有与这些蛋白质的结合口袋相互作用的潜力，突出了其作为治疗化合物减轻FEN诱导的肝损伤的能力。
