Dalteparin as a Novel Therapeutic Agent to Prevent Diabetic Encephalopathy by Targeting Oxidative Stress and Inflammation

Introduction: Hepcidin is the principal modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown hepcidin plays an important role for in neuronal iron load and inflammation. This is of significance because neuronal iron load and inflammation are pathophysiological processes that have been highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models. Methods: Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200–250 g were classified into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg i.p) and insulin (100 mg/kg S.C) were administered for eight weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out.  The animals were perfused randomly and their hippocampal tissue was isolated for analysis of markers such as lipid peroxidation (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for measurement of serum inflammatory cytokine IL-6. Results: The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevent its decline. Conclusion: Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer’s disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may promote the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and suggested to be considered as a potential therapeutic agent in diabetes.