Sulforaphane reduces the alterations induced by quinolinic acid: Modulation of glutathione levels

• QUIN decreased the level of GSH in the rat striatum.
• SULF avoid the decrease of GSH levels in the rat striatum.
• SULF increased enzymes activity related to regeneration of GSH levels.
• SULF ameliorated the QUIN-induced behavioral and morphological alterations.

Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5 mg/kg, i.p.) 24 h and 5 min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4 h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24 h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.