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.

中文翻译：

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去铁胺调节糖尿病引起的认知功能障碍大鼠的神经炎症和氧化应激。

糖尿病性脑病是糖尿病的主要并发症，其特征在于认知障碍以及结构和神经化学异常。铁稳态失衡后的神经炎症是几种神经系统疾病的显着特征。在本研究中，我们调查了作为临床铁螯合剂的去铁胺（DFO）在改善1型糖尿病诱发的认知功能障碍中的作用。链脲佐菌素用于在大鼠模型中诱导1型糖尿病。将动物分为四组：对照组，糖尿病，糖尿病+铁和糖尿病+ DFO。因此，DFO的剂量为100 mg / kg SC，铁的剂量为12 mg / kg PO，持续8周。最后，进行了Y迷宫和被动回避。IL-6，铁蛋白，ELISA法检测脑源性神经营养因子（BDNF）的表达。我们的结果显示铁蛋白（ 与对照组相比，糖尿病和铁组的 IL-6（P <0.001），IL-6（P  <0.001），MDA（P  <0.01）以及BDNF水平降低（P <0.001）。糖尿病诱发后8周用DFO治疗后，铁蛋白（P  <0.001），IL-6（P  <0.01）和MDA（P  <0.001）显着降低，而BDNF（ 与糖尿病组和铁组相比，P＜0.01）。总的来说，这些发现证明了DFO作为通过靶向氧化应激，神经炎症和铁稳态调节来减轻糖尿病后认知功能障碍的良好候选者的有效性。