Anti-embolic and anti-oxidative effects of a novel (E)-4-amino-N′-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against isoproterenol and vitamin-K induced ischemic stroke

Abstract This study aimed to evaluate the cerebroprotective potential of a novel synthetic coumarin, (E)-4-amino-N′-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene) benzohydrazide noted (HC) against a pharmaceutically induced ischemic stroke in experimental male Wistar rats. Animals were randomly allocated into four groups: control, Stroke, Stroke + Ace (acenocoumarol) and Stroke + HC-treated group for 7 days. Our results showed that stroke group evidenced atrial flutter, significant cardiac hypertrophy (+23%) and increase in plasma level of troponin-T, with disturbance in plasma ionic levels and rise in fibrinogen rate and oxidative damages in heart and brain. Moreover, the histological findings revealed myocardium necrosis, cardiac cavity thrombi and brain injury as compared to normal rats. However, HC-treatment significantly prevents the embolic process, improves cerebral damages and mitigates the oxidative stress markers in stroke rats. Overall, HC is endowed with a thrombolytic potential against MI and stroke in such severe conditions through an anti-vit K (AVK) mechanism.

[1]  S. Larsson,et al.  Circulating Vitamin K1 Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study , 2018, Nutrients.

[2]  A. Skanes,et al.  Elevated Incidence of Atrial Fibrillation and Stroke in Patients With Atrial Flutter-A Population-Based Study. , 2018, The Canadian journal of cardiology.

[3]  J. Healey,et al.  Incident Atrial Fibrillation and Stroke in Patients With Atrial Flutter. , 2018, The Canadian journal of cardiology.

[4]  Hui-Jie Hu,et al.  Disrupted Ionic Homeostasis in Ischemic Stroke and New Therapeutic Targets. , 2017, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[5]  D. Macêdo,et al.  Effects of standard ethanolic extract from Erythrina velutina in acute cerebral ischemia in mice. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  E. Terecoasă,et al.  Etiologic classification of ischemic stroke: Where do we stand? , 2017, Clinical Neurology and Neurosurgery.

[7]  Jeannie K. Lee,et al.  Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses. , 2017, Clinical therapeutics.

[8]  A. Wolberg,et al.  Fibrinogen and Fibrin in Hemostasis and Thrombosis. , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[9]  N. Gharsallah,et al.  Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat , 2016, Cardiovascular Toxicology.

[10]  Young Joon Lee,et al.  Neuroprotective effects of Danggui-Jakyak-San on rat stroke model through antioxidant/antiapoptotic pathway. , 2016, Journal of ethnopharmacology.

[11]  J. Franke,et al.  Cardioembolic Stroke and Postmyocardial Infarction Stroke. , 2016, Cardiology clinics.

[12]  R. Srinivasa,et al.  Acenocoumarol: A Review of Anticoagulant Efficacy and Safety. , 2016, The Journal of the Association of Physicians of India.

[13]  A. Mekaj,et al.  New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events , 2015, Therapeutics and clinical risk management.

[14]  A. Aras,et al.  Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats , 2015, Neural regeneration research.

[15]  F. Sharp,et al.  Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  G. Pignataro,et al.  Does Na+/Ca2+ Exchanger, NCX, Represent a New Druggable Target in Stroke Intervention? , 2014, Translational Stroke Research.

[17]  T. Arumugam,et al.  Pathogenesis of acute stroke and the role of inflammasomes , 2013, Ageing Research Reviews.

[18]  M. Hennerici,et al.  The ASCOD Phenotyping of Ischemic Stroke (Updated ASCO Phenotyping) , 2013, Cerebrovascular Diseases.

[19]  M. Hutyra,et al.  Troponin T in acute ischemic stroke. , 2013, The American journal of cardiology.

[20]  K. N. Venugopala,et al.  Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity , 2013, BioMed research international.

[21]  G. K. Rajanikant,et al.  Oxidative stress--assassin behind the ischemic stroke. , 2012, Folia neuropathologica.

[22]  Craig D Williams,et al.  Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke , 2012, Nature Reviews Neurology.

[23]  B. Nieswandt,et al.  Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke , 2011, Journal of thrombosis and haemostasis : JTH.

[24]  B. Ovbiagele,et al.  Stroke Epidemiology: Advancing Our Understanding of Disease Mechanism and Therapy , 2011, Neurotherapeutics.

[25]  X. Jouven,et al.  Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis , 2011, Circulation.

[26]  C. Shayo,et al.  Coumarins: old compounds with novel promising therapeutic perspectives. , 2010, Current medicinal chemistry.

[27]  L. Vennila,et al.  Protective effect of sesamol against myocardial infarction caused by isoproterenol in Wistar rats , 2010, Redox report : communications in free radical research.

[28]  P. Langhorne,et al.  Elevated Troponin after Stroke: A Systematic Review , 2009, Cerebrovascular Diseases.

[29]  H. Ganther,et al.  Selenium: biochemical role as a component of glutathione peroxidase. , 2009, Science.

[30]  A. Willing.  Experimental Models: Help or Hindrance , 2009, Stroke.

[31]  Anil Kumar,et al.  Pathophysiology and therapeutic strategies in the management of stroke: an update. , 2008, Drugs of today.

[32]  A. Green.  Pharmacological approaches to acute ischaemic stroke: reperfusion certainly, neuroprotection possibly , 2008, British journal of pharmacology.

[33]  E. Warburton,et al.  Inflammation and ischaemic stroke , 2007, Current opinion in neurology.

[34]  A. Słowik,et al.  Increased plasma fibrinogen predicts one-year mortality in patients with acute ischemic stroke , 2006, Journal of the Neurological Sciences.

[35]  P. Mecocci,et al.  Potential markers of oxidative stress in stroke. , 2005, Free radical biology & medicine.

[36]  R. Becker.  The Importance of Factor Xa Regulatory Pathways in Vascular Thromboresistance: Focus on Protein Z , 2005, Journal of Thrombosis and Thrombolysis.

[37]  O. Hurtado,et al.  Inhibition of glutamate release by delaying ATP fall accounts for neuroprotective effects of antioxidants in experimental stroke , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  D. Hanley,et al.  Prevalence and knowledge of transient ischemic attack among US adults , 2003, Neurology.

[39]  F. Terasawa,et al.  Fibrinogens Kosai and Ogasa: Bβ15Gly→Cys (GGT→TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregation , 2003, Journal of thrombosis and haemostasis : JTH.

[40]  J. T. Horan,et al.  Fibrin degradation products, fibrin monomer and soluble fibrin in disseminated intravascular coagulation. , 2001, Seminars in thrombosis and hemostasis.

[41]  Martha J. Radford,et al.  Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation , 2001 .

[42]  M. Di Napoli,et al.  Prognostic Influence of Increased C-Reactive Protein and Fibrinogen Levels in Ischemic Stroke , 2001, Stroke.

[43]  M. Fisher,et al.  An overview of acute stroke therapy: past, present, and future. , 2000, Archives of internal medicine.

[44]  R M Whitlock,et al.  Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study , 2000, BMJ : British Medical Journal.

[45]  S. Stolc,et al.  Effect of stobadine on lipid peroxidation in brain and heart after ischemia and reperfusion of the brain. , 1999, Life sciences.

[46]  P. Lipton,et al.  Ischemic cell death in brain neurons. , 1999, Physiological reviews.

[47]  C. Vermeer,et al.  Modulation of arterial thrombosis tendency in rats by vitamin K and its side chains. , 1997, Atherosclerosis.

[48]  Macrae I Mhairi.  New models of focal cerebral ischaemia. , 1992 .

[49]  J. Sixma,et al.  PLATELET ADHESION , 1990 .

[50]  P N Viswanathan,et al.  A modified spectrophotometric assay of superoxide dismutase. , 1984, Indian journal of biochemistry & biophysics.

[51]  H. Ganther,et al.  Selenium: Biochemical Role as a Component of Glutathione Peroxidase , 1973, Science.

[52]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[53]  Ping Liao,et al.  Oncotic Cell Death in Stroke. , 2019, Reviews of physiology, biochemistry and pharmacology.

[54]  S. Larsson,et al.  Circulating Vitamin K1 Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study , 2018, Nutrients.

[55]  J. Weisel,et al.  Fibrin Formation, Structure and Properties. , 2017, Sub-cellular biochemistry.

[56]  T. Tatlisumak,et al.  Animal models of ischemic stroke. , 2009, Handbook of clinical neurology.

[57]  C. Mărgăritescu,et al.  Histopathological changes in acute ischemic stroke. , 2009, Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie.

[58]  Howard E Gendelman,et al.  Oxidative stress and the pathogenesis of neurodegenerative disorders. , 2007, International review of neurobiology.

[59]  M. Ufer.  Comparative Pharmacokinetics of Vitamin K Antagonists , 2005, Clinical pharmacokinetics.

[60]  A. Arimura,et al.  Filament size influences temperature changes and brain damage following middle cerebral artery occlusion in rats , 2001, Experimental Brain Research.

[61]  C. Fraga,et al.  Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. , 1988, Free radical biology & medicine.

[62]  S. Hatano,et al.  Experience from a multicentre stroke register: a preliminary report. , 1976, Bulletin of the World Health Organization.