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Long-Term Iron Sucrose Administration Induced Oxidative Stress and Vascular Dysfunction in Mice
Wanida Donpunha1, Kwanjit Sompamit2, Upa Kukongviriyapan1*, Poungrat Pakdeechote1, Veerapol Kukongviriyapan3
1Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
2 Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand
3Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Abstract
It has been suggested that iron overload is associated with oxidative stress and implicated in cardiovascular disease. This study is designed to examine whether long-term exposure of iron sucrose induces oxidative stress and vascular dysfunction. Male ICR mice were administered with iron sucrose (10 mg/kg/day; i.p.); three times/week for 8 weeks, while normal control mice were injected with normal saline. After experimental period, mice were anaesthetized with ketamine/xylazine (100:2.5 mg/kg, i.p.), arterial blood pressure was recorded through carotid artery and vascular reactivities to phenylephrine (Phe; 0.03 µmol/kg), acetylcholine (ACh; 10 nmol/kg) and sodium nitroprusside (SNP; 10 nmol/kg) were tested. Blood samples were collected for measurement of serum iron profiles. Tissue samples, including heart, kidney were collected for measurement of the amount of malondialdehyde (MDA), a lipid peroxidation marker. Results indicated that long-term exposure to iron sucrose significantly increased superoxide production and MDA levels. Increased oxidative stress by the iron sucrose was associated with vascular dysfunction, since the vascular responses to vasoactive agents were attenuated when compared with normal controls. These alterations were correlated with the increase in serum iron and ferritin. We for the first time reported the deleterious effect of iron sucrose on the induction of vascular dysfunction and oxidative stress in mice. Supplementation of antioxidants and/or iron chelating agents might be beneficial in this mouse model of iron overload.
Keywords: Iron, Iron sucrose, Oxidative stress, vascular dysfunction
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