Increased Oxidative Stress Toxicity and Lowered Antioxidant Defenses in Temporal Lobe Epilepsy and Mesial Temporal Sclerosis: Associations with Psychiatric Comorbidities.

Abstract

Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), plays a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown. Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl (-SH) groups in depression due to TLE (n = 25); anxiety disorders due to TLE (n = 27); psychotic disorder due to TLE (n = 25); "pure TLE" (n = 27); and healthy controls (n = 40). TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899), and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, while increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels. These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups plays a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology and psychosis, as well as negative and depressive symptoms.

• Authors: Michael Maes, Thitiporn Supasitthumrong, Chusak Limotai, Ana Paula Michelin, Andressa Keiko Matsumoto, Laura de Oliveira Semão, João Victor de Lima Pedrão, Estefânia Gastaldello Moreira, Andre F Carvalho, Sunee Sirivichayakul, Décio Sabbatini Barbosa, Buranee Kanchanatawan
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 57 Issue 8 Pg. 3334-3348 (Aug 2020) ISSN: 1559-1182 [Electronic] United States
• PMID: 32514863 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Nitric Oxide

Topics

• Adult
• Antioxidants (metabolism, pharmacology)
• Depressive Disorder, Major (metabolism, pathology)
• Epilepsy, Temporal Lobe (drug therapy, metabolism)
• Female
• Humans
• Male
• Middle Aged
• Nitric Oxide (metabolism)
• Nitrosative Stress (physiology)
• Oxidative Stress (physiology)
• Psychotic Disorders (complications, metabolism)