Administration of Selenium Decreases Lipid Peroxidation and Increases Vascular Endothelial Growth Factor in Streptozotocin Induced Diabetes Mellitus

The imbalance in oxidant/antioxidant status plays a pivotal role in diabetes mellitus (DM). Selenium is a integral component of the antioxidant enzyme glutathione peroxidase. Se treatment induces angiogenesis and improves endothelial function through increased expression of vascular endothelial growth factor (VEGF). The aim of this study is to investigate the effect of selenium on oxidative stress, VEGF, and endothelin 1 (ET1) in a DM rat model.
We performed an experimental animal study with 64 adult male Wistar-Albino rats. Rats were divided into the following groups (n=8): control (C)7, C21, C늇抺 selenite (Se)7, and C䧭 (control rats), and DM7, DM21, DM䧮, and DM䧭 (diabetic rats). Diabetes was induced by 2-deoxy-2-(3-methyl-3-nitrosoureido)- D-glucopyranose [streptozotocin (STZ)]. Three weeks after STZ, DM䧮 rats received intraperitoneal (i.p.) injections of 0.4 mg/kg Se for 7 days. The DM䧭 rats received these injections for 21 days. The same dose/duration of Se was administered to the C䧮 and C䧭 groups. The remaining rats (C7, C21, DM7, DM21) received physi- ologic saline injections for 7 or 21 days. Ferric reducing antioxidant power (FRAP), malon- dialdehyde (MDA), advanced oxidation protein products (AOPP), and endothelial function markers (VEGF and ET1) in plasma samples were measured.
Diabetic rats (DM7 and DM21) had significantly increased plasma FRAP (P=0.002, P=0.001), AOPP (P=0.024, P=0.01), MDA (P=0.004, P=0.001), and ET1 (P=0.028, P=0.003) levels compared with C7 and C21 control rats. VEGF (P=0.02, P=0.01) significantly decreased in DM7 and DM21 diabetic rats compared with their controls (C7, C21). Se administration reversed the increased MDA and decreased VEGF levels, and lowered plasma glucose levels in the DM䧮 and DM䧭 diabetic groups compared with diabetic rats (DM7, DM21). We observed positive correlations between FRAP-AOPP (r=0.460), FRAP-ET1 (r=0.510), AOPP-MDA (r=0.270), and AOPP-ET1 (r=0.407), and a negative correlation between MDA-VEGF (r=-0.314).
We observed accentuated oxidative stress and impaired endothelial function in diabetes. Se treatment reduced lipid peroxidation and hyperglycemia. Se probably improved endothelial dysfunction in diabetic rats because of the increased VEGF levels.