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Chlorella sorokiniana Extract Prevents Cisplatin-Induced Myelotoxicity In Vitro and In Vivo

机译:小球果索妥尼亚亚洲提取物可防止顺铂诱导体外和体内乳腺毒性

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Cisplatin chemotherapy causes myelosuppression and often limits treatment duration and dose escalation in patients. Novel approaches to circumvent or lessen myelotoxicity may improve clinical outcome and quality of life in these patients. Chlorella sorokiniana (CS) is a freshwater unicellular green alga and exhibits encouraging efficacy in immunomodulation and anticancer in preclinical studies. However, the efficacy of CS on chemoprotection remains unclear. We report here, for the first time, that CS extract (CSE) could protect normal myeloid cells and PBMCs from cisplatin toxicity. Also, cisplatin-induced apoptosis in HL-60 cells was rescued through reservation of mitochondrial function, inhibition of cytochrome c release to cytosol, and suppression of caspase and PARP activation. Intriguingly, cotreatment of CSE attenuated cisplatin-evoked hypocellularity of bone marrow in mice. Furthermore, we observed the enhancement of CSF-GM activity in bone marrow and spleen in mice administered CSE and cisplatin, along with increased CD11b levels in spleen. In conclusion, we uncovered a novel mechanism of CSE on myeloprotection, whereby potentially supports the use of CSE as a chemoprotector against cisplatin-induced bone marrow toxicity. Further clinical investigation of CSE in combination with cisplatin is warranted.
机译:顺铂化疗导致骨髓抑制,经常限制患者的治疗持续时间和剂量升级。旨在规避或减少骨髓毒性的新方法可以改善这些患者的临床结果和生活质量。小球藻(CS)是一种淡水单细胞绿藻,在临床前研究中表现出令人愉快的免疫调节和抗癌的疗效。然而,CS对化学防护的疗效仍然尚不清楚。我们首次报告CS提取物(CSE)可以保护正常的骨髓细胞和来自顺铂毒性的PBMC。此外,通过保留线粒体函数,抑制细胞色素C释放到胞浆溶质和胱天蛋白酶和PARP活化的细胞色素C释放和PARP活化的抑制凋亡诱导的HL-60细胞中的凋亡。有趣的是,COTEATEM对小鼠中的Cisplatin诱发的小鼠骨髓的短细胞度。此外,我们观察到在施用CSE和顺铂的小鼠中提高骨髓和脾脏中的CSF-GM活性,以及​​脾脏的CD11b水平增加。总之,我们发现了CSE在Myellotection的新机制,从而可能支持CSE作为Cisplatin诱导的骨髓毒性的化学冲动器。有必要进一步临床研究CSSE与顺铂组合。

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