PDF(Pubmed)
Abstract：
The flavonoid compound Isorhamnetin (IRMN) is known for its considerable pharmacological properties, which include antioxidant and anti-inflammatory effects, as well as significant protective actions on heart health. However, the potential of IRMN to guard against heart damage caused by cisplatin (CP), a common chemotherapeutic agent, and the specific mechanisms involved, remain unexplored areas. This research was designed to investigate how IRMN counters CP-induced heart toxicity. In our study, mice were orally given IRMN at 50 or 150 mg/kg/day for a week, followed by CP injections (5 mg/kg/day) on the third and sixth days. The animals were euthanized under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) on the eighth day to collect blood and heart tissues for further examination. Our findings reveal that IRMN administration significantly reduced the heart damage and the elevation of heart injury markers such as cardiac troponin I, creatine kinase, and lactate dehydrogenase induced by CP. IRMN also effectively lowered oxidative stress markers, including reactive oxygen species and malondialdehyde, while boosting ATP production and antioxidants like superoxide dismutase, catalase, and glutathione. The compound\'s capability to diminish the levels of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6, alongside modulating apoptosis-regulating proteins (enhancing Bcl-2 while suppressing Bax and Caspase-3 expression), further underscores its cardioprotective effect. Notably, IRMN modulated the p62-Keap1-Nrf2 signaling pathway, suggesting a mechanism through which it exerts its protective effects against CP-induced cardiac injury. These insights underscore the potential of IRMN as an effective adjunct in cancer therapy, offering a strategy to mitigate the cardiotoxic side effects of cisplatin.
摘要：
类黄酮化合物异鼠李素（IRMN）以其可观的药理特性而闻名，其中包括抗氧化和抗炎作用，以及对心脏健康的重大保护行动。然而,IRMN预防顺铂（CP）引起的心脏损害的潜力，一种常见的化疗药物，以及所涉及的具体机制，仍未探索的领域。这项研究旨在研究IRMN如何对抗CP诱导的心脏毒性。在我们的研究中,小鼠以50或150mg/kg/天的剂量口服IRMN，持续一周，然后在第3天和第6天注射CP（5mg/kg/天）。动物在戊巴比妥钠麻醉下安乐死（50mg/kg，腹膜内）在第八天收集血液和心脏组织进行进一步检查。我们的研究结果表明，IRMN管理显着减少心脏损伤和心脏损伤标志物如心肌肌钙蛋白I的升高，肌酸激酶，和CP诱导的乳酸脱氢酶。IRMN还有效降低氧化应激标志物，包括活性氧和丙二醛,同时促进ATP生产和抗氧化剂如超氧化物歧化酶，过氧化氢酶,和谷胱甘肽.该化合物具有降低促炎细胞因子如肿瘤坏死因子-α和白细胞介素-6水平的能力，同时调节凋亡调节蛋白（增强Bcl-2，同时抑制Bax和Caspase-3表达），进一步强调了它的心脏保护作用。值得注意的是,IRMN调节p62-Keap1-Nrf2信号通路，提示其对CP诱导的心脏损伤发挥保护作用的机制。这些见解强调了IRMN作为癌症治疗有效辅助手段的潜力，提供减轻顺铂心脏毒性副作用的策略。
