{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:53:36Z","timestamp":1784908416221,"version":"3.55.0"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ratchadapisek Research Funds","award":["Grant No. RA 57\/024"],"award-info":[{"award-number":["Grant No. RA 57\/024"]}]},{"name":"Islamic University, Najaf, Iraq","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>No precision medicine models of temporal lobe epilepsy (TLE) and associated mental comorbidities have been developed to date. This observational study aimed to develop a precision nomothetic, data-driven comorbid TLE model with endophenotype classes and pathway phenotypes that may have prognostic and therapeutical implications. We recruited forty healthy controls and 108 TLE patients for this research and assessed TLE and psychopathology (PP) features as well as oxidative stress (OSTOX, e.g., malondialdehyde or MDA, lipid hydroperoxides, and advanced oxidation protein products) and antioxidant (paraoxonase 1 or PON1 status, -SH groups, and total radical trapping potential or TRAP) biomarkers. A large part (57.2%) of the variance in a latent vector (LV) extracted from the above TLE and PP features was explained by these OSTOX and antioxidant biomarkers. The PON1 Q192R genetic variant showed indirect effects on this LV, which were completely mediated by PON1 activity and MDA. Factor analysis showed that a common core could be extracted from TLE, PP, OSTOX and antioxidant scores, indicating that these features are manifestations of a common underlying construct, i.e., a novel pathway phenotype of TLE. Based on the latter, we constructed a new phenotype class that is characterized by increased severity of TLE, PP and OSTOX features and lowered antioxidant defenses. A large part of the variance in episode frequency was explained by increased MDA, lowered antioxidant, and nitric oxide metabolite levels. In conclusion, (a) PP symptoms belong to the TLE phenome, and the signal increased severity; and (b) cumulative effects of aldehyde formation and lowered antioxidants determine epileptogenic kindling.<\/jats:p>","DOI":"10.3390\/antiox11050803","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Novel Pathway Phenotype of Temporal Lobe Epilepsy and Comorbid Psychiatric Disorders: Results of Precision Nomothetic Medicine"],"prefix":"10.3390","volume":"11","author":[{"given":"Michael","family":"Maes","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Psychiatry, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria"},{"name":"IMPACT\u2014The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Barwon Health, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9cio Sabbatini","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina 86038-440, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-6731","authenticated-orcid":false,"given":"Abbas F.","family":"Almulla","sequence":"additional","affiliation":[{"name":"Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf 54001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5387-8867","authenticated-orcid":false,"given":"Buranee","family":"Kanchanatawan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","first-page":"630853","article-title":"A review of the epidemiology of temporal lobe epilepsy","volume":"2012","year":"2012","journal-title":"Epilepsy Res. Treat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1528-1157.1975.tb04721.x","article-title":"The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967","volume":"16","author":"Hauser","year":"1975","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.yebeh.2017.12.025","article-title":"Oxidative stress in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis: Possible association with major depressive disorder?","volume":"80","author":"Martins","year":"2018","journal-title":"Epilepsy Behav."},{"key":"ref_4","unstructured":"(NINDS) NIoNDaS (2016). The Epilepsies and Seizures: Hope through Research, National Institutes of Health (NIH)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1684\/epd.2009.0279","article-title":"Temporal lobe epilepsy: Neuropathological and clinical correlations in 243 surgically treated patients","volume":"11","author":"Tassi","year":"2009","journal-title":"Epileptic Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1590\/S0004-282X2011000200003","article-title":"Prevalence of psychiatric comorbidities in temporal lobe epilepsy in a Southern Brazilian population","volume":"69","author":"Bragatti","year":"2011","journal-title":"Arq. Neuro-Psiquiatr."},{"key":"ref_7","first-page":"163731","article-title":"Epilepsy, mental health disorder, or both?","volume":"2012","author":"Beletsky","year":"2012","journal-title":"Epilepsy Res. Treat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.seizure.2010.07.004","article-title":"Psychiatric disorders in temporal lobe epilepsy: An overview from a tertiary service in Brazil","volume":"19","author":"Kummer","year":"2010","journal-title":"Seizure"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.0013-9580.2004.47003.x","article-title":"The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy","volume":"45","author":"Johnson","year":"2004","journal-title":"Epilepsia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"795259","DOI":"10.1155\/2012\/795259","article-title":"Oxidative stress and epilepsy: Literature review","volume":"2012","author":"Aguiar","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0009-8981(00)00337-5","article-title":"Oxidative stress and antioxidants in epilepsy","volume":"303","author":"Sudha","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.eplepsyres.2009.09.020","article-title":"Mitochondria, oxidative stress, and temporal lobe epilepsy","volume":"88","author":"Waldbaum","year":"2010","journal-title":"Epilepsy Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1007\/s12035-020-01949-8","article-title":"Increased Oxidative Stress Toxicity and Lowered Antioxidant Defenses in Temporal Lobe Epilepsy and Mesial Temporal Sclerosis: Associations with Psychiatric Comorbidities","volume":"57","author":"Maes","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"308","DOI":"10.5498\/wjp.v12.i2.308","article-title":"Lowered paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy or mesial temporal sclerosis and depression, anxiety, and psychosis","volume":"12","author":"Michelin","year":"2022","journal-title":"World J. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"745613","DOI":"10.1155\/2015\/745613","article-title":"Seizure-induced oxidative stress in temporal lobe epilepsy","volume":"2015","author":"Puttachary","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.neuropharm.2007.01.010","article-title":"Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c\/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat","volume":"52","author":"Chuang","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1528-1167.2008.01778.x","article-title":"Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation of mitochondrial apoptotic signaling in hippocampal CA3 subfield following experimental temporal lobe status epilepticus","volume":"50","author":"Chuang","year":"2008","journal-title":"Epilepsia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0920-1211(00)00096-6","article-title":"Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies","volume":"40","author":"Kyllerman","year":"2000","journal-title":"Epilepsy Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"398","DOI":"10.4103\/0972-2327.144008","article-title":"Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress","volume":"17","author":"Menon","year":"2014","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.2174\/1570159X17666181227164947","article-title":"Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?","volume":"17","author":"Moreira","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.pnpbp.2010.05.004","article-title":"A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness","volume":"35","author":"Maes","year":"2011","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhong, S., Liao, X., Chen, J., He, T., Lai, S., and Jia, Y. (2015). A Meta-Analysis of Oxidative Stress Markers in Depression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138904"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.jad.2021.07.057","article-title":"Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders","volume":"294","author":"Morelli","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s12640-018-9906-2","article-title":"Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses","volume":"34","author":"Maes","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.niox.2020.11.001","article-title":"Construction of a nitro-oxidative stress-driven, mechanistic model of mood disorders: A nomothetic network approach","volume":"106","author":"Simeonova","year":"2021","journal-title":"Nitric Oxide"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s11011-020-00656-6","article-title":"Towards a new model and classification of mood disorders based on risk resilience, neuro-affective toxicity, staging, and phenome features using the nomothetic network psychiatry approach","volume":"36","author":"Maes","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5498\/wjp.v11.i1.1","article-title":"How to construct neuroscience-informed psychiatric classification? Towards nomothetic networks psychiatry","volume":"11","author":"Stoyanov","year":"2021","journal-title":"World J. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.yebeh.2004.08.003","article-title":"The interictal dysphoric disorder: Recognition, pathogenesis, and treatment of the major psychiatric disorder of epilepsy","volume":"5","author":"Blumer","year":"2004","journal-title":"Epilepsy Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br. J. Med. Psychol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"799","DOI":"10.2466\/pr0.1962.10.3.799","article-title":"The Brief Psychiatric Rating Scale","volume":"10","author":"Overall","year":"1962","journal-title":"Psychol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-Mental State. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0891-5849(91)90002-K","article-title":"Hydroperoxide-initiated chemiluminescence: An assay for oxidative stress in biopsies of heart, liver, and muscle","volume":"10","author":"Flecha","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10549-011-1693-x","article-title":"Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy","volume":"133","author":"Panis","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ab.2012.01.016","article-title":"Quantitation of malondialdehyde in gingival crevicular fluid by a high-performance liquid chromatography-based method","volume":"423","author":"Bastos","year":"2012","journal-title":"Anal. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.cca.2012.01.038","article-title":"Improved detection of advanced oxidation protein products in plasma","volume":"413","author":"Hanasand","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ki.1996.186","article-title":"Advanced oxidation protein products as a novel marker of oxidative stress in uremia","volume":"49","author":"Friedlander","year":"1996","journal-title":"Kidney Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/clinchem\/44.3.679","article-title":"Semiautomated measurement of nitrate in biological fluids","volume":"44","author":"Arenas","year":"1998","journal-title":"Clin. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1161\/CIRCGENETICS.108.811638","article-title":"Determination of paraoxonase 1 status without the use of toxic organophosphate substrates","volume":"1","author":"Richter","year":"2008","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_40","first-page":"1335","article-title":"Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters","volume":"28","author":"Billecke","year":"2000","journal-title":"Drug Metab. Dispos."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1097\/00008571-200012000-00002","article-title":"Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds","volume":"10","author":"Li","year":"2000","journal-title":"Pharmacogenetics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1161\/hq0901.094247","article-title":"Paraoxonase status in coronary heart disease: Are activity and concentration more important than genotype?","volume":"21","author":"Mackness","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.clinbiochem.2008.09.120","article-title":"The measurement of the lactonase activity of paraoxonase-1 in the clinical evaluation of patients with chronic liver impairment","volume":"42","author":"Marsillach","year":"2009","journal-title":"Clin. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cbi.2016.08.007","article-title":"The effect of HDL-bound and free PON1 on copper-induced LDL oxidation","volume":"257","author":"Bayrak","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0009-8981(96)06394-2","article-title":"Oxidative stress in blood of HIV infected patients","volume":"255","author":"Repetto","year":"1996","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0076-6879(94)33044-1","article-title":"Measurement of protein thiol groups and glutathione in plasma","volume":"233","author":"Hu","year":"1994","journal-title":"Methods Enzymol."},{"key":"ref_47","first-page":"275","article-title":"The analytical performance of a microplatemethod for total sulfhydryl measurement in biological samples","volume":"35","author":"Taylan","year":"2010","journal-title":"Turk. J. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"iii","DOI":"10.2307\/41410402","article-title":"A critical look at the use of PLS-SEM in \u201cMIS Quarterly\u201d","volume":"36","author":"Ringle","year":"2012","journal-title":"MIS Q."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1108\/EBR-11-2018-0203","article-title":"When to use and how to report the results of PLS-SEM","volume":"31","author":"Hair","year":"2019","journal-title":"Eur. Bus. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1007\/s12035-019-1552-z","article-title":"Development of a Novel Staging Model for Affective Disorders Using Partial Least Squares Bootstrapping: Effects of Lipid-Associated Antioxidant Defenses and Neuro-Oxidative Stress","volume":"56","author":"Maes","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0014-4886(69)90128-9","article-title":"A permanent change in brain function resulting from daily electrical stimulation","volume":"25","author":"Goddard","year":"1969","journal-title":"Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.neubiorev.2007.04.003","article-title":"Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena","volume":"31","author":"Post","year":"2007","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jad.2021.03.062","article-title":"In schizophrenia, immune-inflammatory pathways are strongly associated with depressive and anxiety symptoms, which are part of a latent trait which comprises neurocognitive impairments and schizophrenia symptoms","volume":"287","author":"Almulla","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jaroonpipatkul, C., Onwanna, J., Tunvirachaisakul, C., Jittapiromsak, N., Rakvongthai, Y., Chutinet, A., and Maes, M. (J. Affect. Disord., 2022). Depressive symptoms due to stroke are strongly predicted by the volume and location of the cerebral infarction, white matter hyperintensities, hypertension, and age: A nomothetic network analysis, J. Affect. Disord., in press.","DOI":"10.1016\/j.jad.2022.04.041"},{"key":"ref_56","first-page":"1","article-title":"A pathway phenotype linking metabolic, immune, oxidative, and opioid pathways with comorbid depression, atherosclerosis, and unstable angina","volume":"27","author":"Mousa","year":"2021","journal-title":"CNS Spectr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1136\/bmj.325.7356.149","article-title":"Depression in medical patients","volume":"325","author":"Peveler","year":"2002","journal-title":"BMJ"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Maes, M., and Stoyanov, D. (Res. Gate Prepr., 2022). False dogmas in mood disorders research: Towards a nomothetic network approach, Res. Gate Prepr., in press.","DOI":"10.5498\/wjp.v12.i5.651"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lorigados Pedre, L., Morales Chac\u00f3n, L.M., Pav\u00f3n Fuentes, N., Robinson Agramonte, M.L.A., Serrano S\u00e1nchez, T., Cruz-Xenes, R.M., D\u00edaz Hung, M.L., Estupi\u00f1\u00e1n D\u00edaz, B., B\u00e1ez Mart\u00edn, M.M., and Orozco-Su\u00e1rez, S. (2018). Follow-Up of Peripheral IL-1\u03b2 and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery. Behav. Sci., 8.","DOI":"10.3390\/bs8020021"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1007\/s12035-020-02047-5","article-title":"Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: A Nomothetic Network Psychiatry Approach","volume":"57","author":"Maes","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1086\/651257","article-title":"Reconsidering Baron and Kenny: Myths and Truths about mediation anaysis","volume":"37","author":"Zhao","year":"2010","journal-title":"J. Cosumer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1037\/1082-989X.7.4.422","article-title":"Mediation in Experimental and Nonexperimental Studies: New Procedures and Recommendations","volume":"7","author":"Shrout","year":"2002","journal-title":"Psychol. Methods"},{"key":"ref_63","unstructured":"Hayes, A.F. (2013). Introduction to Mediation, Moderation, and Conditional Process Analysis, Guilfold Press."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4103\/0971-4065.41282","article-title":"Serum paraoxonase activity and protein thiols in chronic renal failure patients","volume":"18","author":"Prakash","year":"2008","journal-title":"Indian J. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.2337\/diacare.20.10.1589","article-title":"Total plasma antioxidant capacity predicts thrombosis-prone status in NIDDM patients","volume":"20","author":"Ceriello","year":"1997","journal-title":"Diabetes Care"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"300","DOI":"10.5152\/turkjnephrol.2021.20004","article-title":"The Relationship between Dietary Total Antioxidant Capacity with Serum Antioxidant and Oxidant Parameters in Hemodialysis Patients","volume":"30","author":"Ozkalayci","year":"2021","journal-title":"Turk. J. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0891-5849(98)00272-X","article-title":"Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants","volume":"26","author":"Aviram","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.bcp.2004.08.027","article-title":"Modulation of paraoxonase (PON1) activity","volume":"69","author":"Costa","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.2217\/pgs.13.147","article-title":"Pharmacogenetics of paraoxonase activity: Elucidating the role of high-density lipoprotein in disease","volume":"14","author":"Kim","year":"2013","journal-title":"Pharmacogenomics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.3748\/wjg.v13.i14.2053","article-title":"Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents","volume":"13","author":"Nagy","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1007\/s12035-016-9975-2","article-title":"Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome","volume":"54","author":"Morris","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3389\/fnbeh.2017.00203","article-title":"Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior","volume":"11","author":"Zhu","year":"2017","journal-title":"Front. Behav. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.niox.2019.07.003","article-title":"Upregulation of the nitrosylome in bipolar disorder type 1 (BP1) and major depression, but not BP2: Increased IgM antibodies to nitrosylated conjugates are associated with indicants of leaky gut","volume":"91","author":"Maes","year":"2019","journal-title":"Nitric Oxide"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.seizure.2012.09.003","article-title":"Oxidative stress in patients with epilepsy is independent of antiepileptic drugs","volume":"21","author":"Menon","year":"2012","journal-title":"Seizure"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tashakori-Miyanroudi, M., Ramazi, S., Hashemi, P., Nazari-Serenjeh, M., Baluchnejadmojarad, T., and Roghani, M. (2022). Acetyl-L-Carnitine Exerts Neuroprotective and Anticonvulsant Effect in Kainate Murine Model of Temporal Lobe Epilepsy. J. Mol. Neurosci., 1\u201310.","DOI":"10.1007\/s12031-022-01999-8"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Essawy, A.E., El-Sayed, S.A., Tousson, E., Abd El-Gawad, H.S., Alhasani, R.H., and Abd Elkader, H.A.E. (2022). Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy. Environ. Sci. Pollut. Res. Int., 1\u201315.","DOI":"10.1007\/s11356-022-19251-6"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"108611","DOI":"10.1016\/j.yebeh.2022.108611","article-title":"An aqueous extract of Lantana camara attenuates seizures, memory impairment, and anxiety in kainate-treated mice: Evidence of GABA level, oxidative stress, immune and neuronal loss modulation","volume":"129","author":"Kandeda","year":"2022","journal-title":"Epilepsy Behav."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"15","DOI":"10.31083\/j.jin2101015","article-title":"Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2\/HO-1, IGF-1 signaling pathways cross talk","volume":"21","author":"Yehia","year":"2022","journal-title":"J. Integr. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2174\/1570159X12666140923205715","article-title":"Antioxidants as a preventive treatment for epileptic process: A review of the current status","volume":"12","author":"Martinc","year":"2014","journal-title":"Curr. Neuropharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Majkowski, J., Westermarck, T., and Atroshi, F. (2020). Free Radicals and Antioxidants: Opportunities for Enhancing Treatment of Epilepsy with Personalized Medicine. Personalized Medicine, in Relation to Redox State, Diet and Lifestyle, Intech. Available online: https:\/\/www.who.int\/en\/activities\/tracking-SARS-CoV-2-variants\/.","DOI":"10.5772\/intechopen.91999"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1002\/ptr.6617","article-title":"Natural polyphenols in preclinical models of epilepsy","volume":"34","author":"Dhir","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1007\/s12035-021-02720-3","article-title":"N-acetylcysteine aggravates seizures while improving depressive-like and cognitive impairment comorbidities in the WAG\/Rij rat model of absence epilepsy","volume":"59","author":"Tallarico","year":"2022","journal-title":"Mol. Neurobiol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/5\/803\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:29Z","timestamp":1760137049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/5\/803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":82,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["antiox11050803"],"URL":"https:\/\/doi.org\/10.3390\/antiox11050803","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.07.22270647","asserted-by":"object"}]},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}