Mitochondria and oxidative stress in epilepsy: advances in antioxidant therapy

被引:0
作者
Ji, Delphine [1 ,2 ]
Mylvaganam, Shanthini [1 ]
Chander, Prathyusha Ravi [1 ]
Tarnopolsky, Mark [3 ]
Murphy, Keiran [1 ]
Carlen, Peter [1 ,2 ,4 ]
机构
[1] Krembil Res Inst, Toronto, ON, Canada
[2] Univ Toronto, Dept Med & Physiol, Toronto, ON, Canada
[3] McMaster Childrens Hosp, Dept Pediat, Hamilton, ON, Canada
[4] Univ Toronto, Biomed Engn, Toronto, ON, Canada
关键词
epilepsy; antioxidant therapy; oxidative stress; mitochondrial dysfunction; reactive oxygen species; PENTYLENETETRAZOL-INDUCED SEIZURES; DELTA-AMINOLEVULINIC DEHYDRATASE; K+-ATPASE ACTIVITY; ALPHA-TOCOPHEROL; KAINIC ACID; DNA-DAMAGE; RAT MODEL; MOLECULAR-MECHANISMS; LIPID-PEROXIDATION; STATUS EPILEPTICUS;
D O I
10.3389/fphar.2024.1505867
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Epilepsy, affecting approximately 50 million individuals worldwide, is a neurological disorder characterized by recurrent seizures. Mitochondrial dysfunction and oxidative stress are critical factors in its pathophysiology, leading to neuronal hyperexcitability and cell death. Because of the multiple mitochondrial pathways that can be involved in epilepsy and mitochondrial dysfunction, it is optimal to treat epilepsy with multiple antioxidants in combination. Recent advancements highlight the potential of antioxidant therapy as a novel treatment strategy. This approach involves tailoring antioxidant interventions-such as melatonin, idebenone, and plant-derived compounds-based on individual mitochondrial health, including mitochondrial DNA mutations and haplogroups that influence oxidative stress susceptibility and treatment response. By combining antioxidants that target multiple pathways, reducing oxidative stress, modulating neurotransmitter systems, and attenuating neuroinflammation, synergistic effects can be achieved, enhancing therapeutic efficacy beyond that of a single antioxidant on its own. Future directions include conducting clinical trials to evaluate these combination therapies, and to translate preclinical successes into effective clinical interventions. Targeting oxidative stress and mitochondrial dysfunction through combination antioxidant therapy represents a promising adjunctive strategy to modify disease progression and improve outcomes for individuals living with epilepsy.
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页数:10
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共 143 条
[1]   Melissa officinalis L. ameliorates oxidative stress and inflammation and upregulates Nrf2/HO-1 signaling in the hippocampus of pilocarpine-induced rats [J].
Abd Allah, Hagar N. ;
Abdul-Hamid, Manal ;
Mahmoud, Ayman M. ;
Abdel-Reheim, Eman S. .
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 2022, 29 (02) :2214-2226
[2]   The potential antiepileptic activity of astaxanthin in epileptic rats treated with valproic acid [J].
Abdulqader, Yussra Ata Yaseen ;
Kawy, Hala Salah Abdel ;
Alkreathy, Huda Mohammed ;
Rajeh, Nisreen Abdullah .
SAUDI PHARMACEUTICAL JOURNAL, 2021, 29 (05) :418-426
[3]   Neuroprotective Effects of Idebenone Against Pilocarpine-Induced Seizures: Modulation of Antioxidant Status, DNA Damage and Na+, K+-ATPase Activity in Rat Hippocampus [J].
Ahmed, Maha Ali Eissa .
NEUROCHEMICAL RESEARCH, 2014, 39 (02) :394-402
[4]   The Neuroprotective Effect Associated with Echinops spinosus in an Acute Seizure Model Induced by Pentylenetetrazole [J].
Alkhudhayri, Abdulsalam ;
Moneim, Ahmed E. Abdel ;
Rizk, Sara ;
Bauomy, Amira A. ;
Dkhil, Mohamed A. .
NEUROCHEMICAL RESEARCH, 2023, 48 (01) :273-283
[5]   Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis [J].
Almeida, Cayo ;
Pongilio, Renan Paschoalino ;
Movio, Marilia Ines ;
Higa, Guilherme Shigueto Vilar ;
Resende, Rodrigo Ribeiro ;
Jiang, Jianxiong ;
Kinjo, Erika Reime ;
Kihara, Alexandre Hiroaki .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2022, 10
[6]   The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms [J].
Alshabi, Ali Mohamed ;
Shaikh, Ibrahim Ahmed ;
Asdaq, Syed Mohammed Basheeruddin .
SAUDI JOURNAL OF BIOLOGICAL SCIENCES, 2022, 29 (05) :3600-3609
[7]   Proanthocyanidins alleviate pentylenetetrazole-induced epileptic seizures in mice via the antioxidant activity [J].
Alyami, Nouf M. ;
Abdi, Saba ;
Alyami, Hanadi M. ;
Almeer, Rafa .
NEUROCHEMICAL RESEARCH, 2022, 47 (10) :3012-3023
[8]   Neuroprotective Effect of Otostegia limbata Against PTZ-Induced Mice Model of Epilepsy by Attenuated Expression of p-NFκB and TNF-α [J].
Amin, Farhana ;
Tabassum, Sobia ;
Sarwar, Sadia ;
Qureshi, Rahmatullah ;
Sohaib Khalid, Muhammad ;
Riaz, Naveeda ;
Al-Qahtani, Wahidah H. ;
Murtaza, Iram .
FRONTIERS IN NEUROSCIENCE, 2022, 16
[9]   Experimental assessment of bioenergetic differences caused by the common European mitochondrial DNA haplogroups H and T [J].
Amo, Taku ;
Yadava, Nagendra ;
Oh, Richard ;
Nicholls, David G. ;
Brand, Martin D. .
GENE, 2008, 411 (1-2) :69-76
[10]   SEQUENCE AND ORGANIZATION OF THE HUMAN MITOCHONDRIAL GENOME [J].
ANDERSON, S ;
BANKIER, AT ;
BARRELL, BG ;
DEBRUIJN, MHL ;
COULSON, AR ;
DROUIN, J ;
EPERON, IC ;
NIERLICH, DP ;
ROE, BA ;
SANGER, F ;
SCHREIER, PH ;
SMITH, AJH ;
STADEN, R ;
YOUNG, IG .
NATURE, 1981, 290 (5806) :457-465