Iron Overload in Hypercholesterolemic Rats Affects Iron Homeostasis and Serum Lipids but Not Blood Pressure

Abstract

Epidemiologic and experimental data suggest that excess iron may contribute to the development of cardiovascular diseases (CVD). Because increased LDL cholesterol, decreased HDL cholesterol and alteration of systolic blood pressure (SBP) have all been implicated as risk factors for atherosclerosis and related CVD, the present study was designed to determine whether excess iron alters serum lipids and SBP in control and hypercholesterolemic rats. Female Fischer rats were divided into four groups. The control group (C) was fed the control diet, the CI group was fed the control diet and given iron dextran injections, the hypercholesterolemic group (H) was fed a 1 g/100 g cholesterol diet, and the HI group was fed the cholesterol diet and given iron dextran injections. The rats were fed the diets for 8 wk and iron dextran injections were given during wk 6 at doses of 10 mg/d for 5 d. Excess iron reduced (P < 0.01) plasma total cholesterol in rats fed the cholesterol diet (5.31 +/- 0.83 and 3.17 +/- 0.31 mmol/L for H and HI, respectively). Excess iron also resulted in a redistribution of cholesterol among the various lipoprotein fractions, with an increase (P < 0.01) in HDL cholesterol (0.56 +/- 0.12 and 0.85 +/- 0.16 mmol/L for H and HI, respectively) and a decrease (P < 0.01) in LDL cholesterol (4.49 +/- 0.77 and 2.09 +/- 0.26 mmol/L for H and HI, respectively). This redistribution also occurred in the rats fed the control diet. The treatments did not affect SBP or heart rate. The high cholesterol diet affected iron homeostasis; group H had lower transferrin saturation than group C (P < 0.01); group HI had a lower serum iron concentration than group CI but did not differ from group H (P < 0.05). Therefore, we conclude that if iron has any effect on CVD, it is not through its influence on serum lipids and blood pressure.

Fungal siderophores function as protective agents of LDL oxidation and are promising anti‐atherosclerotic metabolites in functional food

“…Hence, desferricoprogen was retained meanwhile coprogen was secreted more effectively than their iron-complexed and iron-uncomplexed counterparts, respectively, influencing negatively the body iron status. Although the total amount of siderophore detected in blood was negligible in comparison to those found in liver or spleen the serum concentration of coprogen was about 0.01 mg/mL (12 lmol/L), about one third of the total serum iron concentration recorded in rats (35.67 l 5.46 lmol/L) [66] and was comparable to that published for humans (18.2 l 5.4 lmol/L) [67]. Frequent blood donation lowering body iron may protect against accelerated atherosclerosis [67,68] but the hypothesized deleterious effects of dietary iron uptake and body iron stores on the atherosclerotic process have been questioned most recently [69,70].…”

Quantification of the Fat Fraction in the Liver Using Dual-Energy Computed Tomography and Multimaterial Decomposition

“…Accordingly, further studies assessing interobserver variability would be needed in terms of imaging and pathology, and the iron-overloaded animal model with hepatic steatosis was not used for the accuracy evaluation of DECT with MMD in the quantification of HFF. There might be some methods to create an iron overload in animal experiments, such as a high-iron diet for several to 12 months, 58-60 intravenous or intramuscular injection of iron dextran or iron sorbitol for several months, 61,62 or injection of an iron oxide MR contrast agent or intravenous iron supplement at the time of the imaging study. However, these methods were not feasible in this study.…”

HFE C282Y Homozygosity Is Associated With Lower Total and Low-Density Lipoprotein Cholesterol

“…22 Excess iron could affect cholesterol metabolism due to increased intracellular oxidative stress, membrane peroxidation, and altered activity of liver enzymes involved in cholesterol metabolism and lipoprotein formation. 22 Patients with hemochromatosis typically have low levels of hepcidin that increase ferroportin expression on macrophages, which decrease intracellular iron. Foam cells in the arterial wall are deteriorated macrophages and may have decreased iron and less oxidative damage.…”