Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia
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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.
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.
참고문헌 (77)
- O’Brien JT, "Vascular dementia", Lancet, 386, pp.1698~1706 (2015)
- Wang J, "Cholinergic deficiency involved in vascular dementia : possible mechanism and strategy of treatment", Acta Pharmacol Sin, 30, pp.879~888 (2009)
- de la Monte SM, "Alzheimer’s disease is type 3 diabetes-evidence reviewed", J Diabetes Sci Technol, 2, pp.1101~1113 (2008)
- Ravona-Springer R, "The association of diabetes and dementia and possible implications for nondiabetic populations", Expert Rev Neurother, 11, pp.1609~1617 (2011)
- Prasad S, "Diabetes mellitus and blood-brain barrier dysfunction : an overview", J Pharmacovigil, 2, pp.125~ (2014)
- Arnold SE, "Brain insulin resistance in type 2diabetes and Alzheimer disease : concepts and conundrums", Nat Rev Neurol, 14, pp.168~181 (2018)
- Murtishaw AS, "Intermittent streptozotocin administration induces behavioral and pathological features relevant to Alzheimer’s disease and vascular dementia", Neuropharmacology, 137, pp.164~177 (2018)
- Sharma B, "Pitavastatin and 4’-hydroxy-3’-methoxyacetophenone(HMAP)reduce cognitive dysfunction in vascular dementia during experimental diabetes", Curr Neurovasc Res, 7, pp.180~191 (2010)
- Sharma B, "Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats", Psychopharmacology(Berl), 215, pp.677~687 (2011)
- Sharma B, "Behavioral and biochemical investigations to explore pharmacological potential of PPAR-gamma agonists in vascular dementia of diabetic rats", Pharmacol Biochem Behav, 100, pp.320~329 (2011)
- Singh G, "Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats", Pharmacol Biochem Behav, 124, pp.27~35 (2014)
- Liu M, "Effect of ulinastatin on the permeability of the blood-brain barrier on rats with global cerebral ischemia", reperfusion injury as assessed by MRI, 2017, pp.85, 412~417
- Ma L, "Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats", Int J Neurosci, 126, pp.463~468 (2016)
- Cui T, "Ulinastatin attenuates brain edema after traumatic brain injury in rats", Cell Biochem Biophys, 71, pp.595~600 (2015)
- Li XF, "Ulinastatin protects brain against cerebral ischemia", reperfusion injury through inhibiting MMP-9 and alleviating loss of ZO-1 and occludin proteins in mice, 2018, pp.302, 68~74
- Guo M, "Ulinastatin attenuates isoflurane-induced cognitive dysfunction in aged rats by inhibiting neuroinflammation and -amyloid peptide expression in the brain", Neurol Res, 41, pp.923~929 (2019)
- Inagaki T, "Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with psychiatric diseases", Biol Psychiatry, 40, pp.800~803 (1996)
- Cao LJ, "Effects of ulinastatin, a urinary trypsin inhibitor, on synaptic plasticity and spatial memory in a rat model of cerebral ischemia", reperfusion injury, 2011, pp.54, 435~442
- Zhang M, "Ulinastatin may significantly improve postoperative cognitive function of elderly patients undergoing spinal surgery by reducing the translocation of lipopolysaccharide and systemic inflammation", Front Pharmacol, 9, pp.1007~ (2018)
- Koga Y, "Urinary trypsin inhibitor suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia", reperfusion rats, 2010, pp.32, 925~932
- Hu CL, "Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation", Clinics(Sao Paulo), 68, pp.1231~1238 (2013)
- Xie X, "Protective effects of Ulinastatin on oxidative stress and inflammation of rat-derived cardiomyocytes H9c2", Am J Transl Res, 11, pp.7094~7103 (2019)
- Jazwa A, "Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism", Antioxid Redox Signal, 14, pp.2347~2360 (2011)
- Huang C, "Effects of sulforaphane in the central nervous system", Eur J Pharmacol, 853, pp.153~168 (2019)
- Akihiro Shiina, "An Open Study of Sulforaphane-rich Broccoli Sprout Extract in Patients with Schizophrenia", Clinical Psychopharmacology and Neuroscience, 13(1), pp.62~67 (2015), 대한정신약물학회
- Axelsson AS, "Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2diabetes", Sci Transl Med, 9, pp.eaah4477~ (2017)
- Gao J, "Sulforaphane alleviates lipopolysaccharide-induced spatial learning and memory dysfunction in mice : the role of BDNFmTOR signaling pathway", Neuroscience, 388, pp.357~366 (2018)
- Ibbotson K, "Nrf2 signaling increases expression of ATP-binding cassette subfamily C mRNA transcripts at the blood-brain barrier following hypoxia-reoxygenation stress", Fluids Barriers CNS, 14, pp.6~ (2017)
- Jang M, "Sulforaphane ameliorates 3-nitropropionic acid-induced striatal toxicity by activating the Keap1-Nrf2-ARE pathway and inhibiting the MAPKs and NF-B pathways", Mol Neurobiol, 53, pp.2619~2635 (2016)
- Zhou Q, "Sulforaphane protects against rotenone-induced neurotoxicity in vivo : Involvement of the mTOR, Nrf2, and autophagy pathways", Sci Rep, 6, pp.32206~ (2016)
- Townsend BE, "Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice", Exp Gerontol, 73, pp.42~48 (2016)
- Lee S, "Sulforaphane alleviates scopolamine-induced memory impairment in mice", Pharmacol Res, 85, pp.23~32 (2014)
- Wang G, "Sulforaphane prevents neuronal apoptosis and memory impairment in diabetic rats", Cell Physiol Biochem, 39, pp.901~907 (2016)
- Jain S, "Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats", Physiol Behav, 164(Pt A), pp.140~150 (2016)
- Jain S, "Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia", Physiol Behav, 152(Pt A), pp.182~193 (2015)
- Sharma P, "Possible involvement of D2", D3 receptor activation in ischemic preconditioning mediated protection of the brain, 2020, pp.1748, 147116~
- Reddy SS, "Implication of altered ubiquitin-proteasome system and ER stress in the muscle atrophy of diabetic rats", Arch Biochem Biophys, 639, pp.16~25 (2018)
- Tekula S, "Withaferin-A attenuates multiple low doses of Streptozotocin(MLD-STZ)induced type 1 diabetes", Biomed Pharmacother, 106, pp.1428~1440 (2018)
- Gupta S, "Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington’s disease", Pharmacol Biochem Behav, 122, pp.122~135 (2014)
- Mirza R, "Beneficial effects of pioglitazone, a selective peroxisome proliferator-activated receptor- agonist in prenatal valproic acid-induced behavioral and biochemical autistic like features in Wistar rats", Int J Dev Neurosci, 76, pp.6~16 (2019)
- Matsumura Y, "Exaggerated vascular and renal pathology in endothelin-B receptor-deficient rats with deoxycorticosterone acetate-salt hypertension", Circulation, 102, pp.2765~2773 (2000)
- Howarth FC, "Long-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats", Exp Physiol, 90, pp.827~835 (2005)
- Kennedy DO, "B Vitamins and the brain : mechanisms, dose and efficacy--a review", Nutrients, 8, pp.68~ (2016)
- Natali A, "Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes", Diabetes, 55, pp.1133~1140 (2006)
- Maryam Safavi, "Protective Effects of Citicoline and Benfotiamine Each Alone and in Combination on Streptozotocin-induced Memory Impairment in Mice", Clinical Psychopharmacology and Neuroscience, 18(1), pp.81~92 (2020), 대한정신약물학회[DOI]
- Guzik TJ, "Mechanisms of increased vascular superoxide production in human diabetes mellitus : role of NAD(P)H oxidase and endothelial nitric oxide synthase", Circulation, 105, pp.1656~1662 (2002)
- Ighodaro OM, "First line defence antioxidantssuperoxide dismutase(SOD), catalase(CAT)and glutathione peroxidase(GPX) : Their fundamental role in the entire antioxidant defence grid", Alex J Med, 54, pp.287~293 (2018)
- Muriach M, "Diabetes and the brain : oxidative stress, inflammation, and autophagy", Oxid Med Cell Longev, 2014, pp.102158~ (2014)
- Armogida M, "The protective role of catalase against cerebral ischemia in vitro and in vivo", Int J Immunopathol Pharmacol, 24, pp.735~747 (2011)
- Patel H, "Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC", Cardiovasc Diabetol, 12, pp.142~ (2013)
- Hop HT, "Activation of NF-kB-mediated TNF-induced antimicrobial immunity is required for the efficient Brucella abortus clearance in RAW 264.7 cells", Front Cell Infect Microbiol, 7, pp.437~ (2017)
- Catrysse L, "Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB", Trends Cell Biol, 27, pp.417~429 (2017)
- Zhao G, "The effect of ulinastatin on hyperglycemia in patients undergoing hepatectomy", J Surg Res, 193, pp.223~228 (2015)
- Liang S, "Ulinastatin reduces the severity of intestinal damage in the neonatal rat model of necrotizing enterocolitis", Med Sci Monit, 25, pp.9123~9130 (2019)
- Wang WK, "Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis", Exp Ther Med, 14, pp.2497~2504 (2017)
- Honda Y, "A case of successful treatment of a patient with hyperglycemia of 2700mg", dL, 2012, pp.30, 254~
- Yano T, "Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats", Anesthesiology, 98, pp.465~473 (2003)
- Zhao J, "Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice", Sci Rep, 9, pp.5790~ (2019)
- Shikimi T, "Existence of a human urinary trypsin inhibitor(urinastatin)-like substance in the rat brain", Jpn J Pharmacol, 60, pp.97~103 (1992)
- Li Y, "Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-B in SD rat hippocampal astrocyte", Biochem Biophys Res Commun, 458, pp.763~770 (2015)
- Guo W, "Urinary Trypsin Inhibitor attenuates acute lung injury by improving endothelial progenitor cells functions", Cell Physiol Biochem, 36, pp.1059~1068 (2015)
- Li G, "Ulinastatin inhibits oxidant-induced endothelial hyperpermeability and apoptotic signaling", Int J Clin Exp Pathol, 7, pp.7342~7350 (2014)
- Kudo Y, "Protective effect of ulinastatin against liver injury caused by ischemia-reperfusion in rats", Jpn J Pharmacol, 60, pp.239~245 (1992)
- Liu B, "Neuroprotective effect of ulinastatin on spinal cord ischemia-reperfusion injury in rabbits", Oxid Med Cell Longev, 2015, pp.624819~ (2015)
- Song F, "Ulinastatin protects against CVB3-induced acute viral myocarditis through Nrf2activation", Inflammation, 41, pp.803~810 (2018)
- Wang S, "Ulinastatin protects rats with myocardial infarction by activating Nrf2", NOS pathway, 2018, pp.22, 8990~8998
- Li X, "Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia", reperfusion injury, 2017, pp.39, 367~373
- Lee JH, "Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway", Neuroscience, 278, pp.31~39 (2014)
- Mao L, "Protective effects of sulforaphane in experimental vascular cognitive impairment : Contribution of the Nrf2 pathway", J Cereb Blood Flow Metab, 39, pp.352~366 (2019)
- "Broccoli for enhanced learning, memory, cognition and longevity: sulforaphane from broccoli functions as a learning/memory/cognitive/longevity-enhancer: sulforaphane, isolated from broccoli among others, increases Tissue inhibitor of metalloproteinases 2 (TIMP2) levels, improves cognition, and decreases age-associated decline in memory and learning, via down regulation of its target genes" (2018)[URL]
- Negi G, "Nrf2 and NF-B modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes", Curr Neurovasc Res, 8, pp.294~304 (2011)
- Shehatou GS, "Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits", Exp Biol Med(Maywood), 241, pp.426~436 (2016)
- Sotokawauchi A, "Aqueous extract of glucoraphanin-rich broccoli sprouts inhibits formation of advanced glycation end products and attenuates inflammatory reactions in endothelial cells", Evid Based Complement Alternat Med, 2018, pp.9823141~ (2018)
- Uddin MS, "Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders", Sci Total Environ, 707, pp.135624~ (2020)
- Itoh K, "An Nrf2", small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements, 1997, pp.236, 313~322
- Imhoff BR, "Extracellular redox status regulates Nrf2 activation through mitochondrial reactive oxygen species", Biochem J, 424, pp.491~500 (2009)
- Birks JS, "Donepezil for dementia due to Alzheimer’s disease", Cochrane Database Syst Rev, 6, pp.CD001190~ (2018)
