POTENSI SOVATELTIDE (IRL-1620) SEBAGAI OBAT NEUROPROTEKTIF MUTAKHIR STROKE ISKEMIK

Jonathan Ricardo Hamonangan, Michael Nobel Simanjuntak, Leonardus Yodi Giovanni

Abstract


Stroke adalah penyebab kematian tertinggi kedua di dunia. Stroke iskemik terjadi pada 88% kasus stroke, sedangkan stroke pendarahan terjadi pada 12% kasus. Baik pada dewasa maupun anak-anak, stroke dapat menyebabkan kecacatan sehingga memengaruhi produktivitas penderita. Namun, pengobatan stroke iskemik secara farmakologis merupakan tantangan bagi dunia kedokteran karena patologi stroke iskemik yang kompleks. Sebagai intervensi mutakhir, Sovateltide (IRL-1620/PMZ-1620) hadir sebagai agonis endothelin B receptors (ETBR) selektif yang prospektif dengan memberikan efek neuroprotektif dan angiogenesis pada stroke iskemik. Meskipun masih dalam uji coba klinis, belum ada studi pustaka yang membahas mengenai potensi Sovateltide sebagai neuroprotektif stroke iskemik. Sebagai solusinya, studi pustaka ini bertujuan untuk mengetahui potensi Sovateltide sebagai obat neuroprotektif mutakhir stroke iskemik. Studi pustaka secara sistematis ini merupakan hasil analisis dan sintesis dari berbagai referensi yang relevan dengan topik di Pubmed dan Google Scholar, dicari menggunakan berbagai kata kunci, dan jangka waktu tidak lebih dari 10 tahun. Sovateltide merupakan agonis ETBR yang paling selektif sehingga mampu memberikan efek neuroprotektif dengan meningkatkan proliferasi, survival rate, diferensiasi, neurogenesis, fusion mitokondria, dan perkembangan sel saraf. Selain itu, Sovateltide juga mampu meningkatkan Vascular Endothelial Growth Factor (VEGF) sehingga menyebabkan angiogenesis pada pembuluh darah otak yang mengalami oklusi. Berdasarkan penelitian, pemberian Sovateltide pada sampel tikus dewasa dan anak- anak dengan middle cerebral arteries occlusion (MCAO) berpotensi menjadi obat neuroprotektif stroke iskemik fase akut dan subakut. Sovateltide memiliki potensi yang baik sebagai obat neuroprotektif mutakhir stroke iskemik. 


Keywords


Sovateltide, IRL-1620, PMZ-1620, ETBR Agonist, Ischemic Stroke

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References


Campbell BCV , De Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM, et al. Ischaemic stroke. Nat Rev Dis Prim [Internet]. 2019;5(1). Available from: http://dx.doi.org/10.1038/s415 72-019-0118-8

Hankey GJ. Stroke. Lancet. 2017;389(10069):641–54.

Kemenkes R. Infodantin Stroke Kemenkes Ri 2019. Infodantin Stroke Kemenkes RI 2019. 2019.

Johnson W, Onuma O, Owolabi M, Sachdev S. Stroke: A global response is needed [Internet]. V ol. 94, Bulletin of the World Health Organization. World Health Organization; 2016 [cited 2020 Aug 3]. p. 634-635

Available http://www.who.int/bulletin/v olumes/94/9/16-181636/en/

Feigin VL, Norrving B, Mensah GA. Global Burden of Stroke. Circ Res. 2017;120(3):439–48.

V enketasubramanian N, Y oon BW, Pandian J, Navarro JC. Stroke epidemiology in south, east, and south-east asia: A review. J Stroke. 2017;19(3):286–94.

Abbott AL, Silvestrini M, Topakian R, Golledge J, Brunser AM, de Borst GJ, et al. Optimizing the definitions of stroke, transient ischemic attack, and infarction for research and application in clinical practice. Front Neurol. 2017;8(OCT):1–14.

Mutiarasari D. Ischemic Stroke: Symptoms, Risk Factors, and Prevention. Med Tadulako, J Ilm Kedokt. 2019;1(2):36–44.

Sacco RL, Kasner SE, Broderick JP , Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American heart association/American stroke association. Stroke 2013;44(7):2064–89.

deV eber GA, Kirton A, Booth FA, Yager JY, Wirrell EC, Wood E, et al. Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry. Pediatr Neurol [Internet]. 2017;69:58–70. from: http://dx.doi.org/10.1016/j.ped iatrneurol.2017.01.016

Felling RJ, Sun LR, Maxwell EC, Goldenberg N, Bernard T. Pediatric arterial ischemic stroke: Epidemiology, risk factors, and management. Blood Cells, Mol Dis [Internet]. 2017;67:23–33. Available from: http://dx.doi.org/10.1016/j.bc md.2017.03.003

Cifuentes EG, Hornick MG, Havalad S, Donovan RL, Gulati A. Neuroprotective effect of IRL-1620, an endothelin B receptor agonist, on a pediatric rat model of middle cerebral artery occlusion. Front Pediatr. 2018;6(October)

Antonios N, Silliman S. Treatment of Acute Ischemic Stroke. Stroke. 2013;37–54

Gulati A, Hornick MG, Briyal S, Lavhale MS. A novel neuroregenerative approach using ETB receptor agonist, IRL-1620, to treat CNS disorders. Physiol Res. 2018;67:S95–113.

Secades JJ, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Martínez-Vila E, Ríos J, et al. Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials. J Stroke Cerebrovasc Dis [Internet]. 2016;25(8):1984– 96. Available from: http://dx.doi.org/10.1016/j.jstr okecerebrovasdis.2016.04.010

Meschia JF, Bushnell C, Boden-albala B, Braun LT, Dawn M, Chaturvedi S, et al. AHA / ASA Guideline. Stroke. 2014;45:3754–832.

Fonarow GC, Grau-Sepulveda M V ., Saver JL, Reeves MJ, Cox M, Schwamm LH, et al. Why are acute ischemic stroke patients not receiving IV tPA? Neurology. 2016;87(15):1565–74.

Leonard MG, Briyal S, Gulati A. Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats. Brain Res [Internet]. 2012;1464:14– 23. Available from: http://dx.doi.org/10.1016/j.bra inres.2012.05.005

Karsy M, Brock A, Guan J, Taussky P, Yashar M, Park MS. Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke. Neurosurg Focus. 2017;42(4):1–15.

National Birth Defects Prevention Month | CDC [Internet]. [cited 2020 Jul 6]. Available from: https://www.cdc.gov/ncbddd/b irthdefects/prevention- month.html

Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, et al. Citicoline in the treatment of acute ischaemic stroke: An international, randomised, multicentre, placebo- controlled study (ICTUS trial). Lancet [Internet]. 2012;380(9839):349–57. Available from: http://dx.doi.org/10.1016/S01 40-6736(12)60813-7

Leonard MG, Briyal S, Gulati A. Endothelin B receptor agonist, IRL-1620, reduces neurological damage following permanent middle cerebral artery occlusion in rats. Brain Res [Internet]. 2011;1420:48–58. Available from: http://dx.doi.org/10.1016/j.bra inres.2011.08.075

Briyal S, Shepard C, Gulati A. Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacol Biochem Behav [Internet]. 2014;120:65–72. Available from: http://dx.doi.org/10.1016/j.pbb .2014.02.008

Leonard MG, Gulati A. Endothelin B receptor agonist, IRL-1620, enhances angiogenesis and neurogenesis following cerebral ischemia in rats. Brain Res [Internet]. 2013;1528:28–41. Available from: http://dx.doi.org/10.1016/j.bra inres.2013.07.002

Davenport AP , Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, et al. Endothelin. Pharmacol Rev. 2016;95499.

Dhaun N, Webb DJ. Endothelins in cardiovascular biology and therapeutics. Nat Rev Cardiol [Internet]. 2019;16(8):491–502. Available from: http://dx.doi.org/10.1038/s415 69-019-0176-3

Vignon-Zellweger N, Heiden S, Miyauchi T, Emoto N. Endothelin and endothelin receptors in the renal and cardiovascular systems. Life Sci [Internet]. 2012;91(13– 14):490–500. Available from: http://dx.doi.org/10.1016/j.lfs. 2012.03.026

Li W, Abdul Y, Ward R, Ergul A. Endothelin and diabetic complications: A brain-centric view. Physiol Res. 2018;67:S83–94.

Palmer JC, Barker R, Kehoe PG, Love S. Endothelin-1 is Elevated in Alzheimer’s Disease and Upregulated by Amyloid-β. J Alzheimer’s Dis. 2012;29(4):853–61.

Briyal S, Gulati A. Endothelin- A receptor antagonist BQ123 potentiates acetaminophen induced hypothermia and reduces infarction following focal cerebral ischemia in rats. Eur J Pharmacol [Internet]. 2010;644(1–3):73–9. Available from:http://dx.doi.org/10.1016/j.ejp har.2010.06.071

D’Antoni S, Ranno E, Spatuzza M, Cavallaro S, Catania M V . Endothelin-1 Induces Degeneration of Cultured Motor Neurons Through a Mechanism Mediated by Nitric Oxide and PI3K/Akt Pathway. Neurotox Res. 2017;32(1):58–70.

Hostenbach S, D’haeseleer M, Kooijman R, De Keyser J. The pathophysiological role of astrocytic endothelin-1. Prog Neurobiol [Internet]. 2016;144(2015):88–102. Available from: http://dx.doi.org/10.1016/j.pne urobio.2016.04.009

Laziz I, Larbi A, Grebert D, Sautel M, Congar P , Lacroix MC, et al. Endothelin as a neuroprotective factor in the olfactory epithelium. Neuroscience [Internet]. 2011;172:20–9. Available from: http://dx.doi.org/10.1016/j.neuroscience.2010.10.063

Ranjan AK, Briyal S, Gulati A. Sovateltide ( IRL ‐ 1620 ) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke. Sci Rep [Internet]. 2020;1–17. Avalaiable from: https://doi.org/10.1038/s41598 -020-69673-w

Weilinger NL, Maslieieva V, Bialecki J, Sridharan SS, Tang PL, Thompson RJ. Ionotropic receptors and ion channels in ischemic neuronal death and dysfunction. Acta Pharmacol Sin [Internet]. 2013;34(1):39–48. Available from: http://dx.doi.org/10.1038/aps. 2012.95

Sun M, Jin H, Sun X, Huang S, Zhang F, Guo Z. Free radical damage in ischemia reperfusion injury : An obstacle in acute ischemic stroke after revascularization therapy Acute ischemic stroke is a common cause of morbidity and mortality worldwide . thrombectomy are the main revascularization therapies. Oxid Med CellLongev. 2017;2018:1–17.

Ahrendsen JT, Grewal HS, Hickey SP, Culp CM, Gould EA, Shimizu T, et al. Juvenile striatal white matter is resistant to ischemia-induced damage. Glia. 2016;64(11):1972–86.

Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature [Internet]. 2014;508(1):55–60. Available from: http://dx.doi.org/10.1038/natu re13165

Koyama Y , Regulations of P , functions by Roles in Michinaga S. astrocytic endothelins: the pathophysiological responses of damaged brains. J Pharmacol Sci. 2012;118(4):401–7.

Aslan O, Gurger M, Atescelik M, Kara M, Sen A, Alatas OD, et al. Endothelin-1 Lys198Asn and rs10478694 polymorphism in ischemic stroke. Biomed Res. 2017;28(2):750–4.

Coucha M, Li W, Ergul A. The effect of endothelin receptor A antagonism on basilar artery endothelium-dependent relaxation after ischemic stroke. Life Sci [Internet]. 2012;91(13–14):676–80. Available from: http://dx.doi.org/10.1016/j.lfs. 2012.01.020

Palomares SM, J. Cipolla M. Vascular Protection Following Cerebral Ischemia and Reperfusion. J Neurol Neurophysiol. 2011;01(01):1– 12.

Castañeda MM, Cubilla MA, López-Vicchi MM, Suburo AM. Endothelinergic cells in the subependymal region of mice. Brain Res [Internet]. 2010;1321:20–30. Available from: http://dx.doi.org/10.1016/j.bra inres.2010.01.056

Gulati A. Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia. Curr Neuropharmacol. 2016;14(6):619–26.

Leonard MG, Prazad P Puppala B, Gulati A. Selective Endothelin-B Receptor Stimulation Increases Vascular Endothelial Growth Factor in the Rat Brain during Postnatal Development. Drug Res (Stuttg). 2015;65(11):607–13.

Ranjan AK, Briyal S, Khandekar D, Gulati A. Sovateltide (IRL-1620) affects neuronal progenitors and prevents cerebral tissue damage after ischemic stroke. Can J Physiol Pharmacol. 2020;1–28.

Briyal S, Ranjan AK, Hornick MG, Puppala AK, Luu T, Gulati A. Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with 2019;9(1):1–13.

Zhang J, Jiao J. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis. Biomed Res Int. 2015;2015.

Baser A, Skabkin M, Kleber S, Dang Y, Gülcüler Balta GS, Kalamakis G, et al. Onset of differentiation is post- transcriptionally controlled in adult neural stem cells.Nature. 2019;566(7742):100–4.

Fallini C, Zhang H, Su Y, Silani V, Singer RH, Rossoll W, et al. The Survival of Motor Neuron (SMN) protein interacts with the mRNA- binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons. J Neurosci. 2011;31(10):3914– 25.

Wang F, Tidei JJ, Polich ED, Gao Y , Zhao H, Perrone- Bizzozero NI, et al. Positive feedback between RNA- binding protein HuD and transcription factor SA TB1 promotes neurogenesis. Proc NatlAcadSciUSA. 2015;112(36):E4995–5004.

Koyama Y , Nagae R, Tokuyama S, Tanaka K. I.c.v administration of an endothelin ETB receptor agonist stimulates vascular endothelial growth factor-A production and activates vascular endothelial growth factor receptors in rat brain. Neuroscience [Internet]. 2011;192:689–98. Available from: http://dx.doi.org/10.1016/j.neu roscience.2011.05.058




DOI: https://doi.org/10.26618/aimj.v3i2.4157

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