Erythropoietin (EPO) applies anti-inflammatory, anti-apoptotic, anti-oxidant and cytoprotective effects besides its hematopoietic action. A nonhematopoietic peptide engineered from EPO, ARA 290, interacts selectively with the innate repair receptor and has similar possessions. ARA290 mediates tissue protection without hematopoietic side-effects of EPO which limit its clinical application. Doxorubicin (DOX) is the broad-spectrum chemotherapeutic agent, but its use is limited by the development of nonspecific toxicity on noncancerous tissues especially in cardiac cells. Mechanisms behind the DOX-induced toxicities are enhanced level of oxidative damage, inflammation and apoptosis. In the present study, we have investigated whether ARA290 acts as a chemoprotective agent modulating the cytotoxicity, genotoxicity and oxidative stress induced in vitro by DOX. The genoprotective effect of ARA290 on DOX-induced toxicity in three cell line (HepG2, HGF & Stem cell) were assessed. Cells were treated with ARA290 (50-400 nM) and DOX (1 μM) in pretreatment condition. Cytotoxicity was evaluated using the MTT assay, genoprotective effect of ARA290 were evaluated using the micronucleus test and comet assay. AR290 significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by DOX. Besides, DOX impaired anti-oxidant defense enzyme activities and induced inflammation and apoptotic cell death. ARA290 markedly attenuated DOX induced oxidative stress and protected against DOX induced inflammation and apoptotic cell death. This result proposes that ARA290 can act as a protective agent, reducing DOX-induced DNA damage and oxidative stress, and it is possible that this protection could also extend to cardiac cells.

中文翻译：

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一种经过工程改造的非促红细胞生成素衍生肽ARA290，可减轻阿霉素诱导的遗传毒性和氧化应激。

促红细胞生成素（EPO）除具有造血作用外，还具有抗炎，抗凋亡，抗氧化和细胞保护作用。由EPO（ARA 290）改造的非造血肽与先天性修复受体选择性相互作用，并具有相似的财产。ARA290介导组织保护，而没有EPO的造血副作用，这限制了其临床应用。阿霉素（DOX）是一种广谱化疗药物，但其使用受到非癌性组织（尤其是心脏细胞）非特异性毒性发展的限制。DOX诱导的毒性背后的机制是增强的氧化损伤，炎症和细胞凋亡水平。在本研究中，我们研究了ARA290是否作为调节细胞毒性的化学保护剂，DOX体外诱导的遗传毒性和氧化应激。评估了ARA290对DOX诱导的三种细胞系（HepG2，HGF和干细胞）的毒性的遗传保护作用。在预处理条件下，用ARA290（50-400 nM）和DOX（1μM）处理细胞。使用MTT测定法评价细胞毒性，使用微核试验和彗星测定法评价ARA290的基因保护作用。AR290显着降低了尾巴中DNA的百分比和DOX诱导的微核频率。此外，DOX削弱了抗氧化防御酶的活性，并引起炎症和凋亡细胞死亡。ARA290明显减弱了DOX诱导的氧化应激，并保护其免受DOX诱导的炎症和凋亡性细胞死亡。这个结果表明ARA290可以作为保护剂，