Protective Effects of Citicoline and Benfotiamine Each Alone and in Combination on Streptozotocin-induced Memory Impairment in Mice

Abstract

Objective: Diabetes mellitus is associated with cognitive disorders such as Alzheimer's disease. Studies have shown that citicoline and benfotiamine can improve memory and learning through different mechanism of actions. The aim of this study was to compare the individual effects of benfotiamine (100, 200, 300 mg/kg) and citicoline (50, 100, 250, 500 mg/kg, gavage) and their co-administration on memory impairments in diabetic mice. Methods: Diabetes was induced by a single dose of streptozotocin (STZ, 140 mg/kg, intraperitoneal) and benfotiamine and/or citicoline were administered for three weeks. Memory was evaluated using the object recognition task (ORT) and passive avoidance test (PAT). Results: Results from ORT shows that citicoline at 50, 100, 250, and 500 mg/kg and benfotiamine at 100, 200, and 300 mg/kg and their combination (benfotiamine at 100 mg/kg added to citicoline at 50, 100, and 250 mg/kg) are equally effective in reversing the memory loss induced by STZ (p ＜ 0.001). PAT results demonstrate that citicoline at 100, 250, and 500 mg/kg and benfotiamine at above doses did not improve the latency time when administered separately, but benfotiamine at a fixed dose of 100 mg/kg in the presence of citicoline at 50, 100, and 250 mg/kg increased the latency time and improved memory significantly. Conclusion: In conclusion, in PAT, co-administration of benfotiamine and citicoline was more effective than either alone in improving memory. Regarding ORT, although benfotiamine added to citicoline improved memory notably, the difference between combination therapy and single-drug therapy was not considerable.

Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia

“…This work and our previous works utilized STZ-induced diabetes for induction of endothelial dysfunction, behavioral deficits, and biochemical impairments of vascular dementia [ 8 - 11 ]. Even other research groups have also assessed similar alterations induced by diabetes [ 42 , 44 , 45 ]. Thus, in view of the results of this study and results of previous studies both from our lab and other research groups [ 4 , 8 - 11 , 34 , 42 , 45 ] we can say possibly it is the STZ diabetes which is responsible to induce changes in animals similar to that of phenotypes of vascular dementia.…”

“…Even other research groups have also assessed similar alterations induced by diabetes [ 42 , 44 , 45 ]. Thus, in view of the results of this study and results of previous studies both from our lab and other research groups [ 4 , 8 - 11 , 34 , 42 , 45 ] we can say possibly it is the STZ diabetes which is responsible to induce changes in animals similar to that of phenotypes of vascular dementia. There-fore, in this study diabetes may have impaired learning, memory, reversal learning and executive functioning, via endothelial dysfunction, cholinergic dysfunction, oxidative stress and inflammation.…”

Effects of Piper nigrum fruit and Cinnamum zeylanicum bark alcoholic extracts, alone and in combination, on scopolamine-induced memory impairment in mice

“…Passive avoidance test (PAT) was carried out according to the previously described method by Safavi et al . ( 17 ). Step-through passive avoidance is an effective behavioral task commonly used to determine the function of the brain involved in memory.…”

“…The object recognition test (ORT) was performed, as previously described ( 17 ). ORT was performed in a circular field with a diameter of 35 cm and a height of 30 cm.…”

<p>The Potential Neuroprotective Role of Citicoline in Hepatic Encephalopathy</p>

“…Citicoline is a safe pharmaceutical that is used at high doses in humans (eg, in stroke) or experimental models. 65,66 Therefore, high doses of this drug could be administered in acute situations such as HE and hyperammonemia to prevent brain injury. On the other hand, administration of this drug (eg, at lower doses) in Figure 5 Schematic representation of the effect of citicoline on hyperammonemia and hepatic encephalopathy-induced brain injury.…”