Protective Effect of Sulforaphane on Oxidative Stress and Mitochondrial Dysfunction Associated with Status Epilepticus in Immature Rats

0570500 - FGÚ 2024 RIV US eng J - Článek v odborném periodiku
Folbergrová, Jaroslava - Ješina, Pavel - Otáhal, Jakub
Protective Effect of Sulforaphane on Oxidative Stress and Mitochondrial Dysfunction Associated with Status Epilepticus in Immature Rats.
Molecular Neurobiology. Roč. 60, č. 4 (2023), s. 2024-2035. ISSN 0893-7648. E-ISSN 1559-1182
Grant CEP: GA ČR(CZ) GA18-07908S; GA ČR(CZ) GA22-28265S; GA ČR(CZ) GA21-17564S
Institucionální podpora: RVO:67985823
Klíčová slova: immature rats * status epilepticus * oxidative stress * mitochondrial dysfunction * sulforaphane * protection
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.1, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1007/s12035-022-03201-x

The present study aimed to elucidate the effect of sulforaphane (a natural isothiocyanate) on oxidative stress and mitochondrial dysfunction during and at selected periods following status epilepticus (SE) induced in immature 12-day-old rats by Li-pilocarpine. Dihydroethidium was employed for the detection of superoxide anions, immunoblot analyses for 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels and respiratory chain complex I activity for evaluation of mitochondrial function. Sulforaphane was given i.p. in two doses (5 mg/kg each), at PD 10 and PD 11, respectively. The findings of the present study indicate that both the acute phase of SE and the early period of epileptogenesis (1 week and 3 weeks following SE induction) are associated with oxidative stress (documented by the enhanced superoxide anion production and the increased levels of 3-NT and 4-HNE) and the persisting deficiency of complex I activity. Pretreatment with sulforaphane either completely prevented or significantly reduced markers of both oxidative stress and mitochondrial dysfunction. Since sulforaphane had no direct anti-seizure effect, the findings suggest that the ability of sulforaphane to activate Nrf2 is most likely responsible for the observed protective effect. Nrf2-ARE signaling pathway can be considered a promising target for novel therapies of epilepsy, particularly when new compounds, possessing inhibitory activity against protein–protein interaction between Nrf2 and its repressor protein Keap1, with less “off-target” effects and, importantly, with an optimal permeability and bioavailability properties, become available commercially.
Trvalý link: https://hdl.handle.net/11104/0341796