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Lotusine, an alkaloid from Nelumbo nucifera (Gaertn.), attenuates doxorubicin-induced toxicity in embryonically derived H9c2 cells.
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2020-05-29 , DOI: 10.1007/s11626-020-00466-1
Rajendran Harishkumar 1 , Chinnadurai Immanuel Selvaraj 1
Affiliation  

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 gene Bax and apoptotic executor caspase-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.



中文翻译:

莲ine(Nelumbo nucifera)的一种生物碱(Gaertn。)可减弱阿霉素诱导的源自胚胎的H9c2细胞的毒性。

心脏毒性是阿霉素(DOX)或阿霉素化疗的主要挑战。阿霉素通过心肌细胞中活性氧的失控发展而表现出氧化应激。因此,心肌的失调和功能障碍导致细胞凋亡。已经进行了多种尝试来克服富含抗氧化剂的补充剂来控制自由基的患者的这种副作用。植物基或植物源性化合物更注意治疗患者的此类并发症,以支持治疗,恢复或调节正常代谢。因此,我们的研究集中在用植物复合物荷氨酸预处理胚胎来源的大鼠心肌细胞(H9c2),以防止DOX介导的氧化应激。根据实验 暴露于DOX的细胞已表现出形态异常,例如细胞大小减小,收缩,起泡和染色质凝集,而经莲lotus预处理的细胞即使暴露于DOX后也未观察到此类畸变。在经莲花碱预处理的细胞中观察到内源性抗氧化剂增加,脂质过氧化减少,而暴露于阿霉素的细胞中抗氧化剂随脂质过氧化增加而减少。2',7'-二氯荧光素二乙酸酯(DCF-DA)染色法证实了活性氧种类的减少。在qPCR分析中,经莲氨酸预处理的细胞通过下调促凋亡基因减轻了阿霉素介导的细胞凋亡 然而,即使在暴露于DOX后,在经莲子预处理的细胞中也未观察到这种畸形。在经莲花碱预处理的细胞中观察到内源性抗氧化剂增加,脂质过氧化减少,而暴露于阿霉素的细胞中抗氧化剂随脂质过氧化增加而减少。2',7'-二氯荧光素二乙酸酯(DCF-DA)染色法证实了活性氧种类的减少。在qPCR分析中,经莲氨酸预处理的细胞通过下调促凋亡基因减轻了阿霉素介导的细胞凋亡 然而,即使在暴露于DOX后,在经莲子预处理的细胞中也未观察到这种畸形。在经莲花碱预处理的细胞中观察到内源性抗氧化剂增加,脂质过氧化减少,而暴露于阿霉素的细胞中抗氧化剂随脂质过氧化增加而减少。2',7'-二氯荧光素二乙酸酯(DCF-DA)染色法证实了活性氧种类的减少。在qPCR分析中,经莲氨酸预处理的细胞通过下调促凋亡基因减轻了阿霉素介导的细胞凋亡 2',7'-二氯荧光素二乙酸酯(DCF-DA)染色法证实了活性氧种类的减少。在qPCR分析中,经莲氨酸预处理的细胞通过下调促凋亡基因减轻了阿霉素介导的细胞凋亡 2',7'-二氯荧光素二乙酸酯(DCF-DA)染色法证实了活性氧种类的减少。在qPCR分析中,经莲氨酸预处理的细胞通过下调促凋亡基因减轻了阿霉素介导的细胞凋亡Bax和凋亡执行者caspase -3。发光测定进一步证实了这一点,其在经莲花碱预处理的细胞中产生的发光较少,而在单独用阿霉素处理的细胞中记录的发光较高。总之,本研究表明,莲lotus碱预处理通过增加细胞内抗氧化防御能力,对DOX诱导的氧化应激具有潜在的心脏保护活性。

更新日期:2020-05-29
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