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首页> 外文期刊>Chemotherapy Research and Practice >Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model
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Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model

机译：缺铁大鼠模型中铁羧糖介导的阿霉素诱导的心脏毒性减弱

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Since anthracycline-induced cardiotoxicity (AIC), a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM) modulates the influence of iron deficiency anaemia (IDA) and doxorubicin (3–5 mg per kg body weight [BW]) on oxidativeitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP) rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW), either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction) induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase), nitrosative stress (inducible nitric oxide synthase and nitrotyrosine), inflammation (tumour necrosis factor-alpha and interleukin-6), and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin) that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC.
机译：由于蒽环类引起的心脏毒性（AIC）（一种基于蒽环类的化学疗法的并发症）被认为与铁有关，因此，在接受蒽环类的癌症患者中使用铁进行贫血治疗存在担忧。这项研究评估了静脉内羧化麦芽糖铁（FCM）如何调节铁缺乏性贫血（IDA）和阿霉素（3-5 kg / kg体重[BW]）对自发性高血压卒中中氧化/硝化应激，炎症和心肾功能的影响倾向（SHR-SP）大鼠。 FCM的剂量为重复的小剂量或单次总剂量（每公斤体重15μmg铁），同时或在阿霉素后3天服用。 IDA（限制铁饮食）引起的心脏和肾脏氧化应激（标志物包括丙二醛，过氧化氢酶，铜，锌超氧化物歧化酶和谷胱甘肽过氧化物酶），亚硝化应激（诱导型一氧化氮合酶和亚硝基酪氨酸），炎症（肿瘤坏死因子-α）和白介素6）以及功能/形态异常（左心室舒张末期和收缩末期直径，分数缩短，心肌细胞和毛细血管的密度，caveolin-1表达，肌酐清除率和尿中性粒细胞明胶酶相关的脂蛋白）。阿霉素加重。值得注意的是，用FCM进行铁治疗并不会加重IDA和阿霉素对肾脏的影响，而与铁的给药方案无关。该模型的结果表明静脉内FCM可以与基于蒽环类药物的化疗同时使用，而不会增加AIC的征象。

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