Effect of long-term sodium nitrate administration on diabetes-induced anemia and glucose homeostasis in obese type 2 diabetic male rats

Abstract Purpose Anemia is common in patients with type 2 diabetes. This aims at determining long-term effects of nitrate administration on diabetes-induced anemia in obese type 2 diabetic rats. Methods Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Type 2 diabetes was induced using high-fat diet followed by injection of streptozotocin (30 mg/kg). Sodium nitrate (100 mg/L in drinking water) was administered for six months. After overnight fasting, levels of glucose and erythropoietin (EPO) and complete blood cell count (CBC) were measured at month 0, month 3, and month 6. At month 6, serum iron, and testosterone as well as EPO protein levels and hypoxia-inducible factor-1 (HIF-1) mRNA levels in kidney and liver were measured. Results Nitrate administration decreased serum glucose in diabetic rats by 10% and 15% at months 3 and 6, respectively. Nitrate restored decreased red blood cells count, hemoglobin concentration, and hematocrit to control levels in diabetic rats; in addition, nitrate restored decreased serum, kidney, and liver EPO levels to near normal values. Nitrate also increased HIF-1 mRNA levels in both kidney and liver of diabetic rats. Diabetic rats had lower serum testosterone (37%) and iron (20%) and nitrate restored these parameters to near normal values. Conclusion Long-term and low dose of nitrate had beneficial effects against anemia in obese type 2 diabetic rats; these effects were associated with increased EPO and HIF-1 levels in kidney and liver as well as increased circulating EPO, testosterone, and iron.