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

Abstract

Objective: Vascular Dementia (VaD), is associated with metabolic conditions. Diabetes is a major risk factor for the development of VaD. This study investigates the efficacy of ulinastatin (UTI) and sulforaphane (SUL) in streptozotocin (STZ)-diabetes induced vascular endothelium dysfunction and related dementia. Methods: Single dose STZ (50 mg/kg i.p.) was administered to Albino Wistar rats (male, 200−250 g). Morris water maze and attentional set shifting tests were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE, blood brain barrier (BBB) permeability and histopathological changes were also assessed. UTI (10,000 U/kg) and SUL (25 mg/kg) were used alone as well as in combination, as the treatment drugs. Donepezil (0.5 mg/kg) was used as a positive control. Results: STZ-administered rats showed reduction in body weight, learning, memory, reversal learning, executive functioning, impairment in endothelial function, BBB permeability, increase in serum glucose, brains' oxidative stress, inflammation, AChE-activity, BBB permeability and histopathological changes. Administration of UTI and SUL alone as well as in combination, significantly and dose dependently attenuated the STZ-diabetes-induced impairments in the behavioral, endothelial, and biochemical parameters. Conclusion: STZ administration caused diabetes and VaD which was attenuated by the administration of UTI and SUL. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced VaD.

Possible Prophylactic Effects of Sulforaphane on LPS-Induced Recognition Memory Impairment Mediated by Regulating Oxidative Stress and Neuroinflammatory Proteins in the Prefrontal Cortex Region of the Brain

“…Nevertheless, a limited number of studies have investigated the prophylactic effects of SFN on the cholinergic system. Generally, our results match those that support the evidence of SFN's potential effects on the improvement of the cholinergic system, thus improving learning and memory [24,75]. For instance, in mouse models of scopolamine-induced memory impairment, the administration of SFN (10 or 50 mg/kg) to C57BL/6 mice via oral gavage for 2 weeks significantly reduced AChE activity in the frontal cortex [24].…”

Ulinastatin ameliorated streptozotocin-induced diabetic nephropathy: Potential effects via modulating the components of gut-kidney axis and restoring mitochondrial homeostasis

“…Previous research on the effect of UTI on blood glucose levels has yielded conflicting results. Sharma et al found that UTI had no significant effect on hyperglycemia in STZ-induced DM [ 32 ], whereas Zhao et al found that UTI administration improves stress-induced hyperglycemia by reducing inflammation and improving insulin resistance [ 46 ]. These controversies could be explained by different models used in different studies.…”