Lotusine, an alkaloid fromNelumbo nucifera(Gaertn.), attenuates doxorubicin-induced toxicity in embryonically derived H9c2 cells
Lotusine, an alkaloid fromNelumbo nucifera(Gaertn.), attenuates doxorubicin-induced toxicity in embryonically derived H9c2 cells
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DOI：
10.1007/s11626-020-00466-1
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发表时间：
2020-05-01
影响因子：
2.1
通讯作者：
Selvaraj, Chinnadurai Immanuel
中科院分区：
文献类型：
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作者：
Harishkumar, Rajendran;Selvaraj, Chinnadurai Immanuel
阿霉素（DOX）或阿霉素（ADM）化疗的主要挑战是药物毒性。阿霉素通过心肌细胞中活性氧的不受控制的进展表现出氧化应激;因此，心肌的失调和功能障碍导致细胞凋亡。已经进行了几次尝试，以克服这种副作用的患者与抗氧化剂丰富的补充剂，以控制自由基。基于植物或植物衍生的化合物更加关注治疗患者的此类并发症，以支持治疗，振兴或调节正常代谢。因此，我们的研究集中在预处理胚胎来源的大鼠心肌细胞（H9 C2）与植物化合物莲花碱，以防止DOX介导的氧化应激。从实验中，暴露于DOX的细胞显示出形态异常，如细胞大小减小、收缩、起泡和染色质凝聚，而即使在暴露于DOX后，在莲花碱预处理的细胞中也没有观察到这种畸形。增加内源性抗氧化剂与减少脂质过氧化作用，观察在莲心预处理的细胞，而抗氧化剂减少沿着随着脂质过氧化作用增加阿霉素暴露的细胞。用2 '，7'-二氯荧光素二乙酸酯（DCF-DA）染色法证明活性氧产生减少。在qPCR分析中，莲花素预处理的细胞通过下调促凋亡基因和凋亡执行体caspase-3减轻了阿霉素介导的凋亡。这进一步证实了与发光测定，这导致在莲心预处理的细胞较少的发光，而较高的发光记录在阿霉素单独处理的细胞。总之，本研究表明，洛土辛预处理表现出潜在的心脏保护活性，对阿霉素诱导的氧化应激，通过增加细胞内的抗氧化防御。
Cardiotoxicity is the major challenge in chemotherapy with doxorubicin (DOX) or adriamycin. Doxorubicin manifests oxidative stress via an uncontrolled progression of reactive oxygen species in cardiomyocytes; thereby, dysregulation and dysfunction of myocardium thus lead to apoptosis. Several attempts have been made to overcome this side effect in patients with antioxidant-rich supplements to control the free radicals. Plant-based or plant-derived compounds pay more attention to cure such complications in patients for supporting the treatment, revitalizing or regulating the normal metabolism. Hence, our study focused on pretreatment of embryonically derived rat cardiomyocytes (H9c2) with phytocompound lotusine to prevent DOX-mediated oxidative stress. From the experiment, the DOX-exposed cells have shown morphological abnormalities such as reduced cell size, shrinkage, blebbing, and chromatin condensation, whereas no such deformities were observed in lotusine-pretreated cells even after the exposure to DOX. Increased endogenous antioxidants with reduced lipid peroxidation were observed in lotusine-pretreated cells, whereas the antioxidants were reduced along with increased lipid peroxidation in doxorubicin-exposed cells. A decreased reactive oxygen species generation was evidenced with the 2 ',7 '-dichlorofluorescein diacetate (DCF-DA) staining method. In qPCR analysis, the lotusine-pretreated cells have mitigated doxorubicin-mediated apoptosis by downregulating the pro-apoptotic geneBaxand apoptotic executorcaspase-3. It was further confirmed with the luminometric assay, which resulted in lesser luminescence in lotusine-pretreated cells, whereas higher luminescence was recorded in doxorubicin-alone-treated cells. In conclusion, the present study revealed that the lotusine pretreatment has exhibited potential cardioprotective activity against DOX-induced oxidative stress by increasing the intracellular antioxidant defense.