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 oxidative/nitrosative 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. 1. Introduction Cytotoxic cancer treatments frequently include anthracyclines [1]. However, their use is associated with a risk of anthracycline-induced cardiotoxicity (AIC) leading to acute transient arrhythmias, chronic cardiomyopathy, and heart failure [2]. It is hypothesised that AIC results from anthracycline-mediated radical reactions and production of reactive oxygen species (ROS), which may involve anthracycline-iron complexes [3–5]. Considering that anaemia and iron deficiency (ID) are frequent complications in cancer patients [6, 7] and require iron supplementation [8, 9], clinicians are concerned that concomitant use of anthracyclines and iron might increase AIC. However, anaemia and ID should be treated since anaemia is associated with fatigue and impaired response to cancer treatment and survival [10–12]. Furthermore, even ID alone can increase oxidative/nitrosative stress in the heart [13]. Among available iron treatments, oral iron salts are often poorly tolerated whereas
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