Wang Yahui, Hassan Hesham M, Nisar Abdullah, Zahara Syeda Sania, Akbar Ali, Al-Emam Ahmed
School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
J Trace Elem Med Biol. 2025 Feb;87:127588. doi: 10.1016/j.jtemb.2025.127588. Epub 2025 Jan 3.
Vanadium (VAN) is a significant trace element, but its higher exposure is reported to cause severe organ toxicity. Tectochrysin (TEC) is a naturally derived flavonoid which demonstrates a wide range of pharmacological properties.
The current study was planned to assess the cardioprotective potential of TEC against VAN induced cardiotoxicity in rats via regulating biochemical, and histological profile.
Thirty-six male Sprague Dawley rats were apportioned into four groups including the control, VAN (1.5 mg/kg) treated, VAN (1.5 mg/kg) + TEC (2.5 mg/kg) administrated as well as TEC (2.5 mg/kg) alone supplemented group. The doses were administrated for 28 days through oral gavage. The biochemical and histological parameters were evaluated by using qRT-PCR, ELISA, biochemical assays, histological as well as molecular simulation techniques.
VAN intoxication reduced the activities of catalase (CAT) (84.25 %), glutathione peroxidase (GPx) (65.28 %), glutathione reductase (GSR) (78.52 %), heme oxygenase-1 (HO-1) (81.81 %), superoxide dismutase (SOD) (83.71 %) and glutathione (GSH) (76.86 %) contents while upregulating the levels of reactive oxygen species (ROS) (87.26 %) and malondialdehyde (MDA) (91.32 %). Moreover, VAN administration increased the gene expressions of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) (91.47 %), monocyte chemoattractant protein-1 (MCP-1) (92.51 %), interleukin-6 (IL-6) (83.63 %), tumor necrosis factor-alpha (TNF-α) (89.43 %), janus kinase 1 (JAK1) (95.55 %), signal transducer and activator of transcription 3 (STAT3) (91.25 %), nuclear factor-kappa B (NF-κB) (81.31 %), interleukin-18 (IL-18) (93.27 %), interleukin-1 beta (IL-1β) (85.79 %) and cyclooxygenase-2 (COX-2) (82.12 %). The levels of CK-MB (89.43 %), BNP (91.73 %), NT-proBNP (93.64 %), CPK (87.56 %), LDH (92.62 %), troponin I (94.25 %), troponin T (97.53 %) and CRP (88.45 %) were increased following the VAN intoxication. Besides, VAN exposure upregulated the levels of Caspase-9 (89.52 %), Bax (95.52 %) and Caspase-3 (92.52 %) while reducing the levels of Bcl-2 (75.66 %). The structural integrity of cardiac tissues was extensively disrupted following VAN-induced intoxication. However, TEC treatment remarkably ameliorated cardiotoxicity via regulating abovementioned dysregulations induced by VAN exposure. At the end, molecular docking (MD) analysis was accomplished to confirm the potential protective effect of TEC against VAN prompted cardiac dysfunction. It was detected that TEC can strongly bind with the active site of JAK1, NF-kB and STAT3 which also confirm its cardioprotective effect against VAN provoked cardiac dysfunction.
VAN intoxication instigated cardiac impairments which is evident by dysregulations in biochemical as well as histological profile of cardiac tissues. Nonetheless, TEC treatment remarkably protected the cardiac tissues via regulating oxidative stress, inflammation and apoptosis. TEC could be employed as cardioprotective agent against VAN induced cardiotoxicity.
钒（VAN）是一种重要的微量元素，但据报道其高暴露会导致严重的器官毒性。柚皮素（TEC）是一种天然衍生的黄酮类化合物，具有广泛的药理特性。
本研究旨在通过调节生化和组织学特征，评估TEC对钒诱导的大鼠心脏毒性的心脏保护潜力。
将36只雄性Sprague Dawley大鼠分为四组，包括对照组、钒（1.5mg/kg）处理组、钒（1.5mg/kg）+TEC（2.5mg/kg）给药组以及单独补充TEC（2.5mg/kg）组。通过口服灌胃给药28天。使用qRT-PCR、ELISA、生化分析、组织学以及分子模拟技术评估生化和组织学参数。
钒中毒降低了过氧化氢酶（CAT）（84.25%）、谷胱甘肽过氧化物酶（GPx）（65.28%）、谷胱甘肽还原酶（GSR）（78.52%）、血红素加氧酶-1（HO-1）（81.81%）、超氧化物歧化酶（SOD）（83.71%）和谷胱甘肽（GSH）（76.86%）的活性，同时上调了活性氧（ROS）（87.26%）和丙二醛（MDA）（91.32%）的水平。此外，钒给药增加了核苷酸结合结构域、富含亮氨酸家族、含pyrin结构域3（NLRP3）（91.47%）、单核细胞趋化蛋白-1（MCP-1）（92.51%）、白细胞介素-6（IL-6）（83.63%）、肿瘤坏死因子-α（TNF-α）（89.43%）、janus激酶1（JAK1）（95.55%）、信号转导和转录激活因子3（STAT3）（91.25%）、核因子-κB（NF-κB）（81.31%）、白细胞介素-18（IL-18）（93.27%）、白细胞介素-1β（IL-1β）（85.79%）和环氧化酶-2（COX-2）（82.12%）的基因表达。钒中毒后，肌酸激酶同工酶（CK-MB）（89.43%）、脑钠肽（BNP）（91.73%）、N末端脑钠肽前体（NT-proBNP）（93.64%）、肌酸磷酸激酶（CPK）（87.56%）、乳酸脱氢酶（LDH）（92.62%）、肌钙蛋白I（94.25%）、肌钙蛋白T（97.53%）和C反应蛋白（CRP）（88.45%）的水平升高。此外，钒暴露上调了半胱天冬酶-9（Caspase-9）（89.52%）、 Bax（95.52%）和半胱天冬酶-3（Caspase-3）（92.52%）的水平，同时降低了Bcl-2（75.66%）的水平。钒诱导的中毒后，心脏组织的结构完整性受到广泛破坏。然而，TEC治疗通过调节钒暴露引起的上述失调，显著改善了心脏毒性。最后，完成了分子对接（MD）分析，以确认TEC对钒引发的心脏功能障碍的潜在保护作用。检测到TEC可以与JAK1、NF-κB和STAT3的活性位点强烈结合，这也证实了其对钒引发的心脏功能障碍的心脏保护作用。
钒中毒引发心脏损伤，这在心脏组织的生化和组织学特征失调中很明显。尽管如此，TEC治疗通过调节氧化应激、炎症和细胞凋亡，显著保护了心脏组织。TEC可作为对抗钒诱导的心脏毒性的心脏保护剂。
