Iron chelation alleviates multiple pathophysiological pathways in a rat model of cardiac pressure overload

• Published in: Free radical biology & medicine 2023-05, Vol.200, p.1-10
• Main Authors: Lupu, Mihai, Coada, Camelia Alexandra, Tudor, Diana-Valentina, Baldea, Ioana, Florea, Adrian, Toma, Vlad-Alexandru, Lupsor, Ana, Moldovan, Remus, Decea, Nicoleta, Filip, Gabriela Adriana
• Format: Article
• Language: English
• Subjects: Animals; Chelation; Chronic heart failure; Deferiprone; Heart Failure, Systolic; Hypertension; Inflammation - chemically induced; Iron; Iron Chelating Agents - pharmacology; Iron metabolism; Iron Overload - chemically induced; Iron Overload - drug therapy; Lipid peroxidation; Rats
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.02.018

Iron dysmetabolism affects a great proportion of heart failure patients, while chronic hypertension is one of the most common risk factors for heart failure and death in industrialized countries. Serum data from reduced ejection fraction heart failure patients show a relative or absolute iron deficiency, whereas cellular myocardial analyses field equivocal data. An observed increase in organellar iron deposits was incriminated to cause reactive oxygen species formation, lipid peroxidation, and cell death. Therefore, we studied the effects of iron chelation on a rat model of cardiac hypertrophy. Suprarenal abdominal aortic constriction was achieved surgically, with a period of nine weeks to accommodate the development of chronic pressure overload. Next, deferiprone (100 mg/kg/day), a lipid-permeable iron chelator, was administered for two weeks. Pressure overload resulted in increased inflammation, fibrotic remodeling, lipid peroxidation, left ventricular hypertrophy and mitochondrial iron derangements. Deferiprone reduced cardiac inflammation, lipid peroxidation, mitochondrial iron levels, and hypertrophy, without affecting circulating iron levels or ejection fraction. In conclusion, metallic molecules may pose ambivalent effects within the cardiovascular system, with beneficial effects of iron redistribution, chiefly in the mitochondria. Created using www.biorender.com. [Display omitted] •Iron metabolism is an essential yet potentially dangerous micronutrient that appears to be implicated in cardiovascular diseases.•Chronic cardiac stress induced by hypertension leads to inflammation, oxidative stress, fibrosis, and iron derangements.•Iron chelation can reduce oxidative stress, inflammation, and fibrosis in chronic heart failure.