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Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress.

02:58 EDT 19th May 2013 | BioPortfolio

Summary of "Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress."

Adverse reactions to antipsychotic drugs (APs) have been attributed to oxidative stress. Sulforaphane (SF) is a potent antioxidant that protects against dopaminergic cell death. We examined the protective properties of SF against AP-induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK-N-SH cells were treated with SF (0.5-5 μm), and 24 h later, haloperidol, risperidone or paliperidone (100 μm) was administered, either alone or in combination with dopamine (100 μm). To determine the antioxidant properties of SF, quinone oxidoreductase (NQO1) activity, glutathione S-transferase activity, and glutathione (GSH) levels were determined. Oxidative stress was measured by the increase in thiobarbituric acid reactive substances (TBARS) and in protein-bound quinones. Cell viability was also assessed. SF treatment increased GSH levels and induced NQO1 activity in SK-N-SH cells. Haloperidol was the only AP that increased TBARS when administered alone. When cells were cocultured with a drug in combination with dopamine, all three APs increased TBARS and protein-bound quinones and also induced neurotoxicity. In all the experimental conditions, 5 μm SF attenuated the accumulation of TBARS and protein-bound quinones and increased cell survival rates. Our results indicate that SF increases GSH levels and induces NQO1 activity and the removal of electrophilic quinones and radical oxygen species. Furthermore, SF could provide protective effects against AP-induced toxicity in dopaminergic cells.

Affiliation

Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Centro de Investigación Biomédica en R

Journal Details

This article was published in the following journal.

Name: Fundamental & clinical pharmacology
ISSN: 1472-8206
Pages:

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Medical and Biotech [MESH] Definitions

Oxidative Stress

A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).

Tert-butylhydroperoxide

A direct-acting oxidative stress-inducing agent used to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. It is also used as a catalyst in polymerization reactions and to introduce peroxy groups into organic molecules.

Chlorogenic Acid

A naturally occurring phenolic acid which is a carcinogenic inhibitor. It has also been shown to prevent paraquat-induced oxidative stress in rats. (From J Chromatogr A 1996;741(2):223-31; Biosci Biotechnol Biochem 1996;60(5):765-68).

Protein Carbonylation

The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.

Activating Transcription Factor 3

An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.

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