Hemosiderina, um possível biomarcador para sudep?
DOI:
https://doi.org/10.34024/rnc.2021.v29.12514Palavras-chave:
Epilepsia, SUDEP, espécies reativas de oxigênioResumo
A epilepsia é uma das doenças neurológicas de etiologia complexa que afeta em torno de 50 milhões de pessoas em todo o mundo, e é caracterizada por atividade elétrica anormal e convulsões recorrentes. As convulsões tônico-clônicas generalizadas repetitivas descontroladas (GTCS) são as principais causas de morte súbita inesperada em epilepsia (SUDEP). O estresse hipóxico induzido pela crise epiléptica resulta em disfunções neurocardiogênica, incluindo a sobrecarga de ferro a cardiomiopatia (IOC) que está relacionada à peroxidação lipídica grave causada pela produção de espécies reativas de oxigênio (ROS). A ROS induz a atividade convulsiva recorrente, favorecendo a superexpressão da glicoproteína P (P-gp) no coração. A P-gp desempenha uma função despolarizante em membranas de cardiomiócitos e os canais de potássio (Kir) controlam a excitabilidade celular quanto a repolarização do potencial de ação cardíaco. Todos esses acontecimentos resultam num possível aparecimento de bradicardia severa e arritmia fatal. Diversos estudos têm buscado evidências para diferentes possíveis biomarcadores para potencial previsão do risco de SUDEP evitando seu desfecho fatal.
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Fisher RS, Boas WVE, Blume W, Elger C, Genton P, Lee P, et al. Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-2. https://doi.org/10.1111/j.0013-9580.2005.66104.x
Taborda F, Rocha L, Enrique A, Goicoechea S, Casta R, Orozco S, et al. New model of pharmacoresistant seizures induced by 3-mercaptopropionic acid in mice. Epilepsy Res 2017;129:8-16. https://doi.org/10.1016/j.eplepsyres.2016.10.012
Scorza F, Tucci PJF. Sudden Death in Brazil: Epilepsy Should be in Horizon. Arq Bras Cardiol 2015;105:197-8. https://doi.org/10.5935/abc.20150072
Sveinsson O, Andersson T, Mattsson P, Carlsson S. Clinical risk factors in SUDEP. Neurology 2020;94:e419-29. https://doi.org/10.1212/WNL.0000000000008741
Auzmendi J, Akyuz E, Lazarowski A. The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP). Epilepsy Behav 2019;121:106590. https://doi.org/10.1016/j.yebeh.2019.106590
Akyuz E, Doganyigit Z, Eroglu E, Moscovicz F, Merelli A. Myocardial Iron Overload in an Experimental Model of Sudden Unexpected Death in Epilepsy Front Neurol 2021;12:1-9. https://doi.org/10.3389/fneur.2021.609236
Scorza FA, Arida RM, Albuquerque M, Cavalheiro EA. Sudden death in epilepsy: All roads lead to the heart. Rev Ass Med Bras 2008;54:199-200. https://doi.org/10.1590/s0104-42302008000300008
Wu X, Li Y, Zhang S, Zhou X. Ferroptosis as a novel therapeutic target for cardiovascular disease. Theranostics 2021;11:3052-9. https://doi.org/10.7150/thno.54113
Fang X, Wang H, Han D, Xie E, Yang X, Wei J, et al. Ferroptosis as a target of protection against cardiomyopathy. Proc Nat Acad Sci 2019;116:2672-80. https://doi.org/10.1073/pnas.1821022116
Li J, Cao F, Yin Hl, Huang Z, Lin Z, Mao N, et al. Ferroptosis: past, present and future. Cell Death Dis 2020;11:88. https://doi.org/10.1038/s41419-020-2298-2
Kahn-Kirby A, Amagata A, Maeder C, Mei J, Sideris S, Kosaka Y, et al. Targeting ferroptosis: a novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. PLoSOne 2019;14:e0214250. https://doi.org/10.1371/journal.pone.0214250
Yang WS, Stockwell BR. Ferroptosis: Death by Lipid Peroxidation. Trends Cell Biol 2016;26:165-76. https://doi.org/10.1016/j.tcb.2015.10.014
Shen L, Lin D, Li X, Wu H, Lenahan C, Pan Y, et al. Ferroptosis in Acute Central Nervous System Injuries: The Future Direction? Front Cell Develop Biol 2020;8:594. https://doi.org/10.3389/fcell.2020.00594
Shuang C, Yongmin C, Yukang Z, Xi K, Yan L, Meiwen G, et al. Iron Metabolism and Ferroptosis in Epilepsy. Front Neurosci 2020;14:1-16. https://doi.org/10.3389/fnins.2020.601193
Zhang L, Zou X, Zhang B, Cui L, Zhang J, Mao Y, et al. Label-free imaging of hemoglobin degradation and hemosiderin formation in brain tissues with femtosecond pump-probe microscopy. Theranostics 2018;8:4129-40. https://doi.org/10.7150/thno.26946
Li Y, Thom M, Jacques TS. Novel therapeutic targets in epilepsy: oxidative stress and iron metabolism. Neuropathol App Neurobiol 2020;46:519-21. https://doi.org/10.1111/nan.12615
Piperno A, Pelucchi S, Mariani R. Inherited iron overload disorders. Transl Gastroenterol Hepatol 2020;5:25. https://doi.org/10.21037/tgh.2019.11.15
Zimmer T, Ciriminna G, Arena A, Anink J, Korotkov A, Jansen F. Chronic activation of anti-oxidant pathways and iron accumulation in epileptogenic malformations. Neuropathol Appl Neurobiol 2020;46:546-63. https://doi.org/10.1111/nan.12596
Peng P, Peng J, Yin F, Deng X, Chen C, He F, et al. Ketogenic Diet as a Treatment for Super-Refractory Status Epilepticus in Febrile Infection-Related Epilepsy Syndrome. Front Neurol 2019;10:423. https://doi.org/10.3389/fneur.2019.00423
Auzmendi J, Lazarowski A. Seizures Induces Hypoxia and Hypoxia Induces Seizures. A Perverse Relationship that Increases the Risk of SUDEP. Neurol Dis Epilepsy J 2020;3:135. http://hdl.handle.net/11336/134927
Marelli A, Czornyj L, Rocha L, Lazarowski A. Erythropoietin as Potential Neuroprotective and Antiepileptogenic Agent in Epilepsy and Refractory Epilepsy. In: Talevi A, Rocha L (eds). Antiepileptic Drug Discovery. Methods in Pharmacology and Toxicology. New York: Humana Press; 2016; p147-61. https://doi.org/10.1007/978-1-4939-6355-3_8
Auzmendi J, Akyuz E, Lazarowski A. The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP). Epilepsy Behav 2019;121:106590. https://doi.org/10.1016/j.yebeh.2019.106590
Doganyigit Z, Eroglu E, Moscovicz F, Merelli A, Lazarowski A, Auzmendi J. Myocardial Iron Overload in an Experimental Model of Sudden Unexpected Death in Epilepsy. Front Neurol 2021;12:4. https://doi.org/10.3389/fneur.2021.609236
Bleakley LE, Soh MS, Bagnall RD, Sadleir LG, Gooley S, Semsarian C, et al. Are Variants Causing Cardiac Arrhythmia Risk Factors in Sudden Unexpected Death in Epilepsy? Front Neurol 2020;11:925. https://doi.org/10.3389/fneur.2020.00925
Ravindran K, Powell KL, Todaro M, O'Brien TJ. The pathophysiology of cardiac dysfunction in epilepsy. Epilepsy Res 2016;127:19-29. https://doi.org/10.1016/j.eplepsyres.2016.08.007
Matteis M, Cecchetto G, Munari G, Balsamo L, Gardiman MP, Giordano R, et al. Circulating miRNAs expression profiling in drug-resistant epilepsy: Up-regulation of miR-301a-3p in a case of sudden unexpected death. Leg Med 2018;31:7-9. https://doi.org/10.1016/j.legalmed.2017.12.003
El Shorbagy HH, Elsayed MA, Kamal NM, Azab AA, Bassiouny MM, Ghoneim IA. Heart-type fatty acid-binding protein as a predictor of cardiac ischemia in intractable seizures in children. J Pediatr Neurosci 2016;11:175-81. https://doi.org/10.4103/1817-1745.193364
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Copyright (c) 2021 Andressa Sampaio Pereira, Patrícia de Morais Ferreira Brandão, Jerónimo A Auzmend, Alberto Lazarowski
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Publicado: 2021-08-05