1.Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia
Poonam SHARMA ; Prachi KAUSHIK ; Swati JAIN ; Brij Mohan SHARMA ; Rajendra AWASTHI ; Giriraj Thirupathirao KULKARNI ; Bhupesh SHARMA
Clinical Psychopharmacology and Neuroscience 2021;19(3):470-489
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 nitriteitrate, 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.
2.Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia
Poonam SHARMA ; Prachi KAUSHIK ; Swati JAIN ; Brij Mohan SHARMA ; Rajendra AWASTHI ; Giriraj Thirupathirao KULKARNI ; Bhupesh SHARMA
Clinical Psychopharmacology and Neuroscience 2021;19(3):470-489
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 nitriteitrate, 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.