Efficacy of ulinastatin and sulforaphane alone or in combination in rat model of streptozotocin diabetes induced vascular dementia
Poonam Sharma 1, Prachi Kaushik 1, Swati Jain 2, B M Sharma 2, Rajendra Awasthi 3, G T Kulkarni 3, Bhupesh Sharma 1, 4*
1Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India, 2Department of Pharmacology, School of Pharmacy, BIT, Meerut, India, 3Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India, 4CNS and CVS Pharmacology, Conscience Research, Delhi, India
Received: July 1, 2020; Revised: December 10, 2020; Accepted: December 11, 2020; Published online: December 11, 2020.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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 (50mg/kg i.p) was administered to Albino Wistar rats (male, 200-250g). Morris water maze (MWM) and attentional set shifting tests (ASST) 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-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE, blood brain barrier (BBB) permeability and histopathological changes were also assessed. UTI (10,000 U kg-1) and SUL (25mgkg-1) were used alone as well as in combination, as the treatment drugs. Donepezil (0.5mgkg-1) 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.
Keywords: Diabetes, dementia, cognitive impairment, endothelium function, ulinastatin, sulforaphane


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