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

Abstract

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.

Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice

“…Dietary supplementation with dried broccoli sprouts (BrSp, a good source of SFN) (300 mg/kg) ameliorated hypertension and improved glucose tolerance in male Long-Evans rats and suppressed visceral fat accumulation in female rats [40]. Pretreatment with SFN (5 mg/kg) significantly reduced the expression of oxidative stress and mitochondrial dysfunction markers in 12-day-old male Wistar rats [41]. Intraperitoneal injection of SFN (10 mg/kg) for 30 days reduced HFD-induced body weight gain in female mice [42].…”

Kidney injury in a murine hemorrhagic shock/resuscitation model is alleviated by sulforaphane’s anti-inflammatory and antioxidant action

“…As an agonist of Nrf2, SFN in uences antioxidation-related molecular processes. SFN has high antioxidant capacity and the ability to inhibit superoxide anion O -2 [34]. It can activate Nrf2, leading to the upregulation of antioxidant proteins, such as HO-1, SOD, and glutathione s-transferase [34].…”

“…SFN has high antioxidant capacity and the ability to inhibit superoxide anion O -2 [34]. It can activate Nrf2, leading to the upregulation of antioxidant proteins, such as HO-1, SOD, and glutathione s-transferase [34]. Kubo et al [35] found that during the aging process of lens epithelial cells, the binding of the promoter of peroxiredoxin 6 (Prdx6) to the Nrf2/ARE regulatory region (357/349) gradually decreased, leading to the generation of oxidation.…”

Beneficial effects of sennoside B on pentylenetetrazole-induced seizures in rats

“…However, they could not demonstrate a particular effect on the development of convulsions. [20][21][22] Studies that reported the beneficial effects of the administration of antioxidants, such as NAC and sulforaphane (SFN), have also been carried out. 23,24 Moreover, PTZ triggers various toxic conditions by possibly supporting oxidation that causes seizures.…”