Deferoxamine regulates neuroinflammation and oxidative stress in rats with diabetes-induced cognitive dysfunction.

Diabetic encephalopathy, a major complication of diabetes, is characterized by cognitive impairment and structural and neurochemical abnormalities. Neuroinflammation following impairment of iron homeostasis is a remarkable feature of several neurological disorders. In the present study, we investigated the role of deferoxamine (DFO), as a clinical iron chelator, in improvement of type 1 diabetes-induced cognitive dysfunction. Streptozotocin was utilized to induce type 1 diabetic in rat model. Animals were categorized into four groups: control, diabetic, diabetic + Iron and diabetic + DFO. Hence, DFO was administered at a dose of 100 mg/kg S.C and iron was administered at a dose of 12 mg/kg P.O for 8 weeks. Finally, Y-maze and passive avoidance were performed. Measurement of IL-6, ferritin, and the brain-derived neurotrophic factor (BDNF) expression was carried out using ELISA. Our results showed significant increased levels of ferritin (P < 0.001), IL-6 (P < 0.001), MDA (P < 0.01), as well as decreased levels of BDNF (P < 0.001) in the diabetic and iron groups compared to control. Post-treatment with DFO for 8 weeks after the induction of diabetes, markedly reduced levels of ferritin (P < 0.001), IL-6 (P < 0.01), and MDA (P < 0.001), as well as increased levels of BDNF (P < 0.01) compared to the diabetic and iron groups was observed. Collectively, these findings demonstrate the validity of DFO as a good candidate to attenuate cognitive dysfunction following diabetes by targeting oxidative stress, neuroinflammation, and modulation of iron homeostasis.