Abstract
Oxidative stress (OS) contributes to the cascade leading to the dysfunction or death of dopaminergic neurons during Parkinson’s disease (PD). A strategy to prevent the OS of dopaminergic neurons may be the use of phytochemicals as inducers of endogenous antioxidants and phase 2 enzymes. In this study, we demonstrated that treatment of the dopaminergic-like neuroblastoma SH-SY5Y cell line with isothiocyanate erucin (ER), a compound of cruciferous vegetables, resulted in significant increases of both total glutathione (GSH) levels and total antioxidant capacity at the cytosolic level. The increase of GSH levels was associated with an increase in the resistance of SH-SY5Y cells to neuronal death, in terms of apoptosis, induced by 6-hydroxydopamine (6-OHDA). The pretreatment of SH-SY5Y cells with ER was also shown to prevent the redox status impairment, in terms of intracellular ROS and O2•− formation, and loss of mitochondrial membrane potential, early events that are initiators of the apoptotic process, induced by 6-OHDA. Last, the antiapoptotic and antioxidant effects of ER were abolished by buthionine sulfoximine, supporting the main role of GSH in the neuroprotective effects recorded by ER. These results suggest that ER may prevent the oxidative damage induced by 6-OHDA.
Highlights
The production and elimination of reactive oxygen species (ROS) called oxidative stress (OS) contributes to the cascade leading to the dysfunction or death of dopaminergic neurons in the substantia nigra (SN) during Parkinson's disease (PD) [1,2,3]
We evaluated whether the higher levels of GSH induced by ER effectively improves the total antioxidant capacity (TAC) of SH-SY5Y
TAC was measured for its ability to quench the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation (ABTS+) and the results are expressed as trolox equivalent (TE) μmol/mg protein
Summary
The production and elimination of reactive oxygen species (ROS) called oxidative stress (OS) contributes to the cascade leading to the dysfunction or death of dopaminergic neurons in the substantia nigra (SN) during Parkinson's disease (PD) [1,2,3]. Among antioxidant endogenous molecules and enzymes, glutathione (GSH) provides the major line of defense for the protection of cells from oxidative and other forms of toxic stress [6]. An effective neuroprotective strategy against OS in dopaminergic neurons could be to reinforce the cellular defense by using phytochemical inducers of antioxidant endogenous molecules. Isothiocyanates (ITCs), derived from the glucosinolate hydrolysis found in abundance in cruciferous vegetables, have recently gained attention as potential neuroprotective compounds that induce antioxidant phase 2 enzymes and molecules through transcription factor. We assessed the neuroprotective effects of ER against 6-hydroxydopamine (6-OHDA)-induced oxidative damage in terms of impairment in intracellular redox state, loss of mitochondrial membrane potential (MMP) and cellular death. ROS, such as H2O2, O2− and OH [15,16]
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