Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 4, July, p. 635–643

doi: 10.17219/acem/62834

PubMed ID: 28691421

Publication type: original article

Language: English

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Effects of long- and short-term darbepoetin-α treatment on oxidative stress, inflammation and endothelial injury in ApoE knockout mice

Evrim Dursun Özdemir1,A,B,C,D, Aysegul Hanikoglu1,D, Aysegul Cort2,B,D,F, Beste Ozben3,A,B, Gultekin Suleymanlar4,A,B, Tomris Ozben1,A,C,E

1 Department of Biochemistry, Faculty of Medicine, Akdeniz University, Antalya, Turkey

2 Department of Nutrition and Dietetics, Faculty of Health Sciences, Sanko University, Gaziantep, Turkey

3 Department of Cardiology, Faculty of Medicine, Marmara University, Istanbul, Turkey

4 Department of Nephrology, Faculty of Medicine, Akdeniz University, Antalya, Turkey

Abstract

Background. Atherosclerosis and atherosclerosis-related complications are the main cause of death in the world. Vascular injury in response to inflammation and enhanced oxidant stress promotes endothelial dysfunction and leads to atherosclerotic lesions.
Objectives. Low-dose treatment with darbepoetin-α may be a potential therapeutic tool for endothelial injury and atherosclerosis.
Material and Methods. In order to study the effect of darbepoetin-α on endothelial injury and atherosclerosis, we used ApoE-/- mice as the atherosclerotic mice model. We monitored atherosclerosis and plaque formation histochemically in ApoE knockout mice at early and late stages of atherosclerosis. Darbepoetin-α was injected intraperitoneally at a dose of 0.1 μg/kg to ApoE-/- mice. The results of 2 ApoE-/- mice groups injected with darbepoetin-α (early and late stages of atherosclerosis) were compared to the results of the corresponding saline injected ApoE-/- mice groups and the control (C57BL/6) mice.
Results. Lipid profile (total cholesterol, triglyceride), inflammation (CRP, IL-6, histamine), endothelial injury (ICAM-1, selectin) and oxidative stress markers (lipid peroxidation, protein oxidation) were significantly increased in 4 atherosclerotic groups compared to the control group. Short-term darbepoetin-α had no marked effects on indicators of inflammation and endothelial injury in the ApoE knockout mice groups compared to the ApoE knockout mice not treated with darbepoetin-α, however, darbepoetin-α significantly decreased 8-isoprostane and protein carbonyl content. Long term darbepoetin-α treatment reduced oxidative stress in ApoE-/- mice.
Conclusion. This study contributes to understanding and elucidating the biochemical changes occurring during early and late stages of atherosclerosis development regarding lipid profile, inflammation, endothelial injury and oxidative stress markers.

Key words

oxidative stress, atherosclerosis, endothelial dysfunction, darbepoetin-α, ApoE knockout mice

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