Effect of long-term sodium nitrate administration on diabetes-induced anemia and glucose homeostasis in obese type ۲ diabetic male rats

Purpose: Anemia is common in patients with type ۲ diabetes. This aims atdetermining long-term effects of nitrate administration on diabetes-induced anemiain obese type ۲ diabetic rats.Methods: Male Wistar rats were divided into ۴ groups: Control, control + nitrate,diabetes, and diabetes + nitrate. Type ۲ diabetes was induced using high-fat dietfollowed by injection of streptozotocin (۳۰ mg/kg). Sodium nitrate (۱۰۰ mg/L indrinking water) was administered for six months. After overnight fasting, levelsofglucose and erythropoietin (EPO) and complete blood cell count (CBC) weremeasured at month ۰, month ۳, and month ۶. At month ۶, serum iron, andtestosterone as well as EPO protein levels and hypoxia-inducible factor-۱ (HIF-۱)mRNA levels in kidney and liver were measured.Results: Nitrate administration decreased serum glucose in diabetic rats by ۱۰% and۱۵% at months ۳ and ۶, respectively. Nitrate restored decreased red blood cellscount, hemoglobin concentration, and hematocrit to control levels in diabetic rats;in addition, nitrate restored decreased serum, kidney, and liver EPO levels to nearnormal values. Nitrate also increased HIF-۱ mRNA levels in both kidney and liverof diabetic rats. Diabetic rats had lower serum testosterone (۳۷%) and iron (۲۰%) andnitrate restored these parameters to near normal values. Conclusion: Long-term andlow dose of nitrate had beneficial effects against anemia in obese type ۲ diabetic rats;these effects were associated with increased EPO and HIF-۱ levels in kidney andliver as well as increased circulating EPO, testosterone, and iron.