Dietary Iron Restriction Improves Muscle Function, Dyslipidemia, and Decreased Muscle Oxidative Stress in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetes mellitus is a chronic degenerative disease characterized by hyperglycemia and oxidative stress. Iron catalyzes free radical overproduction. High iron concentrations have previously been reported to promote an increase in oxidative stress; however, the effect of iron restriction in diabetes has not yet been explored, so we tested to see if iron restriction in diabetic rats reduces oxidative damage and improved muscle function. Wistar rats were assigned to 4 groups: Control; Diabetic; Diabetic rats with a high iron diet, and Diabetic with dietary iron restriction. After 8 weeks the rats were sacrificed, the muscles were extracted to prepare homogenates, and serum was obtained for biochemical measurements. Low iron diabetic rats showed an increase in the development of muscle strength in both muscles. Dietary iron restriction decreased triglyceride concentrations compared to the untreated diabetic rats and the levels of extremely low-density lipoproteins. Aggravation of lipid peroxidation was observed in the diabetic group with a high iron diet, while these levels remained low with iron restriction. Iron restriction improved muscle strength development and reduced fatigue times; this was related to better lipid profile control and decreased oxidant stress markers.

Keywords: diabetes; fatigue; iron; oxidative stress.

Figure 1

Fasting serum glucose (A) and Weight gain (B). Weight gain was determined by subtracting the animals’ weight after eight-week treatments with the diets, determined right before sacrifice, minus the weight at the beginning of the treatments. Data are expressed as the mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron—restricted diet. Different letters (a–c) represent statistically significant differences.

Figure 2

Effect of iron on hemoglobin levels. Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). Different letters represent statistically significant differences. DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.

Figure 3

Effect of iron on muscle strength development in EDL (A), soleus muscle (B) peak tension (open bars) and solid bars (total tension). Effect of iron on fatigue (C) in EDL (open bars) and soleus muscles (solid bars). Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). (A–C) represent the statistically significant differences between the different groups of the peak tension (open bars); a, b represent the statistically significant difference between the different groups of the total tension (solid bars); DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.

Figure 4

Serum levels of cholesterol (A), high-density lipoproteins (HDL) (B), triglycerides (C), and very-low-density lipoproteins (VLDL) (D). Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). Different letters represent statistically significant differences. DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.

Figure 5

Effect of iron on the levels of ROS in muscle homogenates from control rats. Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). Different letters represent statistically significant differences. DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.

Figure 6

Effects of iron on muscle lipid peroxidation. Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). Different letters indicate statistically significant differences. DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.

Figure 7

Effects of dietary iron on total glutathione (A), reduced glutathione (GSH) (B), oxidized glutathione (GSSG) (C), and GSH/GSSG ratio (D). Data are presented as group mean ± standard error. p < 0.05 (n = 6, ANOVA plus Tukey’s post hoc test). Different letters (a,b) indicate statistically significant differences. DB + IO, diabetic rats with iron overload; DB + IR, diabetic rats with iron restriction diet.