Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells

Moreb, Jan S.; Hershko, C; Hasin, Yonathan

doi:10.1007/bf02005821

Cited by 23 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 Conversely, α‐tocopherol, a natural lipid‐soluble antioxidant, is able to interrupt the chain reaction of membrane lipid peroxidation initiated by free radicals and to interfere with iron‐induced lipid peroxidation in liposomes. 19,20,36 Finally, as shown in our heart cell culture studies, deferoxamine removes iron directly from iron‐loaded heart cells, inhibits lipid peroxidation, 16–19 and reverses the abnormalities in cellular contractility and rhythmicity induced by iron.…”

Section: Role Of Ntpi In Myocardial Diseasementioning

confidence: 59%

Pathophysiology of Iron Overload^a

Hershko

Link

Cabantchik

1998

Annals of the New York Academy of Sciences

222

139

View full text Add to dashboard Cite

In thalassemia, iron overload is the joint outcome of excessive iron absorption and transfusional siderosis. While iron absorption is limited by a physiologic ceiling of about 3 mg/d, plasma iron turnover in thalassemia may be 10 to 15 times normal, caused by the wasteful, ineffective erythropoiesis of an enormously expanded erythroid marrow. This outpouring of catabolic iron exceeds the iron-binding capacity of transferrin and appears in plasma as non-transferrin-plasma iron (NTPI). The toxicity of NTPI is much higher than of transferrin-iron as judged by its ability to promote hydroxyl radical formation resulting in peroxidative damage to membrane lipids and proteins. In the heart, this results in impaired function of the mitochrondrial respiratory chain and abnormal energy metabolism manifested clinically in fatal hemosiderotic cardiomyopathy. Ascorbate increases the efficacy of iron chelators by expanding the intracellular chelatable iron pool, but, at suboptimal concentrations is a pro-oxidant, enhancing the catalytic effect of iron in free radical formation. NTPI is removed by i.v. DFO in a biphasic manner and reappears rapidly upon cessation of DFO, lending support to the continuous, rather than intermittent, use of chelators. Unlike DFO and other hexadentate chelators, bidentate chelators such as L1 may produce incomplete intermediate iron complexes at suboptimal drug concentrations.

show abstract

Section: Role Of Ntpi In Myocardial Diseasementioning

confidence: 59%

Pathophysiology of Iron Overload^a

Hershko

Link

Cabantchik

1998

Annals of the New York Academy of Sciences

222

139

View full text Add to dashboard Cite

show abstract

“…Our previous studies in cultured rat heart cells have shown that the rate of low molecular weight iron uptake is more than 300 times that of transferrin iron [18]. Such uptake results in increased myocardial lipid peroxidation leading to impaired mitochondrial inner membrane respiratory enzyme activity, damage to sarcolemmal thiolic enzymes such as 5 0 -nucleotidase and Na,K-ATPase [28], and abnormal contractility [29,30]. These effects are reversed by in vitro treatment with DFO [16,29].…”

Section: Discussionmentioning

confidence: 99%

High nontransferrin bound iron levels and heart disease in thalassemia major

et al. 2008

View full text Add to dashboard Cite

Although the presence of nontransferrin bound plasma iron (NTBI) in transfusional iron overload is well documented, knowledge about its clinical significance is limited. We assessed NTBI levels in a large and homogeneous series of thalassemia patients on regular transfusion and chelation and explored the hypothesis that NTBI levels may be associated with relevant clinical outcomes: in particular, heart disease. Among 174 patients with thalassemia major and intermedia, we showed the presence NTBI in 145 of 174 or 83.3% of cases. NTBI levels correlated with transferrin saturation, age, and ALT, and not with serum ferritin or liver iron concentrations. At a multiple regression analysis, transferrin saturation and heart disease but not age was independent predictors of NTBI. Patients with heart disease had NTBI levels significantly higher than those without. All patients with heart disease had transferrin saturation above 70%, and all were NTBI positive. Conversely, none of the patients without NTBI and/or with transferrin saturation less than 70% had preclinical or clinical heart disease. To our knowledge, this is the first documentation of a link between the presence of NTBI in thalassemic patients with transfusional iron overload and heart disease. Further investigation from these preliminary findings may clarify whether NTBI assessment may have a role in evaluating the risks and optimizing treatment for transfusion-dependent patients. Am. J. Hematol. 84:29-33, 2009. V

show abstract

“…34,35 Cultures were kept at 37°C in an atmosphere of 5% CO 2 and 95% air in Ham F-10 medium containing added 1 mM CaCl 2 , 10% fetal calf serum, and 10% horse serum. The rat cardiomyocyte H9C2 cell line was grown in 5% CO 2 in air in Dulbecco modified Eagle (DMEM) medium supplemented with 10% fetal calf serum, 4.5 g/L D-glucose, glutamine, and antibiotics (all from Biological Industries, Kibbutz Bet Haemek, Israel).…”

Section: Cell Culturesmentioning

confidence: 99%

Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences

Glickstein

Link

et al. 2006

Blood

178

169

View full text Add to dashboard Cite

Labile iron in hemosiderotic plasma and tissue are sources of iron toxicity. We compared the iron chelators deferoxamine, deferiprone, and deferasirox as scavengers of labile iron in plasma and cardiomyocytes at therapeutic concentrations. This comprised chelation of labile plasma iron (LPI) in samples from thalassemia patients; extraction of total cellular iron; accessing labile iron accumulated in organelles and preventing formation of reactive-oxidant species; and restoring impaired cardiac contractility. Neonatal rat cardiomyocytes were used for monitoring chelator extraction of LCI (labile cell iron) as 59 Fe; assessing in situ cell iron chelation by epifluorescence microscope imaging using novel fluorescent sensors for iron and reactive oxygen species (ROS) selectively targeted to organelles, and monitoring contractility by timelapse microscopy. At plasma concentrations attained therapeutically, all 3 chelators eliminated LPI but the orally active chelators rapidly gained access to the LCI pools of cardiomyocytes, bound labile iron, attenuated ROS formation, extracted accumulated iron, and restored contractility impaired by iron overload. The effect of deferoxamine at therapeutically relevant concentrations was primarily by elimination of LPI. The rapid accessibility of the oral chelators deferasirox and deferiprone to intracellular labile iron compartments renders them potentially efficacious for protection from and possibly reversal of cardiac damage induced by iron overload. (Blood. 2006;108: 3195-3203)

show abstract

Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells

Cited by 23 publications

References 24 publications

Pathophysiology of Iron Overload^a

Pathophysiology of Iron Overload^a

High nontransferrin bound iron levels and heart disease in thalassemia major

Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences

Contact Info

Product

Resources

About

Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells

Cited by 23 publications

References 24 publications

Pathophysiology of Iron Overloada

Pathophysiology of Iron Overloada

High nontransferrin bound iron levels and heart disease in thalassemia major

Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences

Contact Info

Product

Resources

About

Pathophysiology of Iron Overload^a

Pathophysiology of Iron Overload^a