title: Ferric carboxymaltose-mediated attenuation of Doxorubicin-induced cardiotoxicity in an iron deficiency rat model.
abstract: 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.
authors.affiliation: Hospital Alemán, Laboratory of Experimental Medicine, School of Medicine, Avenue Pueyrredon 1640, 1118 Buenos Aires, Argentina.
authors.forename: Jorge Eduardo
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: Hospital Alemán, Laboratory of Experimental Medicine, School of Medicine, Avenue Pueyrredon 1640, 1118 Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rivas
authors.affiliation: Hospital Alemán, Laboratory of Experimental Medicine, School of Medicine, Avenue Pueyrredon 1640, 1118 Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.affiliation: Instituto de Química y Fisicoquímica Biológica (UBA-CONICET), Facultad de Farmacia y Bioquímica, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Jorge Fernando
authors.initials: JF
authors.lastname: Giani
authors.affiliation: Vifor (International) AG, Rechenstrasse 37, 9014 St. Gallen, Switzerland.
authors.forename: Felix
authors.identifier: 0000-0003-0794-1105
authors.initials: F
authors.lastname: Funk
authors.affiliation: Vifor Pharma, 1203-4464 Markham Street, Victoria, BC, Canada V8Z 7X8.
authors.forename: Lee
authors.identifier: 0000-0001-6723-8441
authors.initials: L
authors.lastname: Mizzen
authors.affiliation: Instituto de Química y Fisicoquímica Biológica (UBA-CONICET), Facultad de Farmacia y Bioquímica, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando Pablo
authors.initials: FP
authors.lastname: Dominici