Protective effect of N-acetyl- l-cysteine against disulfiram-induced oxidative stress and apoptosis in V79 cells

• Published in: Toxicology and applied pharmacology 2010-11, Vol.248 (3), p.210-216
• Main Authors: Grosicka-Maciąg, Emilia, Kurpios-Piec, Dagmara, Grzela, Tomasz, Czeczot, Hanna, Skrzycki, Michał, Szumiło, Maria, Rahden-Staroń, Iwonna
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Acetylcysteine - pharmacology; AMINO ACIDS; ANIMAL CELLS; ANIMALS; ANTIOXIDANTS; Antioxidants - pharmacology; Antioxidative enzymes; APOPTOSIS; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; CARBOXYLIC ACIDS; Cell Line; CHEMICAL REACTIONS; CONNECTIVE TISSUE CELLS; Cricetinae; Cricetulus; CYSTEINE; Disulfiram; Disulfiram - antagonists & inhibitors; Disulfiram - toxicity; Dose-Response Relationship, Drug; DRUGS; ENZYME ACTIVITY; FIBROBLASTS; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - physiology; GLUTATHIONE; HAMSTERS; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; MAMMALS; Medical sciences; METABOLISM; NAC; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; OXIDATION; Oxidative Stress - drug effects; Oxidative Stress - physiology; PEPTIDES; POLYPEPTIDES; Protein carbonyls; PROTEINS; RADIOPROTECTIVE SUBSTANCES; RESPONSE MODIFYING FACTORS; RODENTS; SOMATIC CELLS; STRESSES; THIOLS; Toxicology; V79 cells; VERTEBRATES
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2010.08.004

This work investigated the effect of N-acetyl- l-cysteine (NAC) on disulfiram (DSF) induced oxidative stress in Chinese hamster fibroblast cells (V79). An increase in oxidative stress induced by DSF was observed up to a 200 μM concentration. It was evidenced by a statistically significant increase of both GSH t and GSSG levels, as well as elevated protein carbonyl (PC) content. There was no increase in lipid peroxidation (measured as TBARS). DSF increased CAT activity, but did not change SOD1 and SOD2 activities. Analysis of GSH related enzymes showed that DSF significantly increased GR activity, did not change Se-dependent GPx, but statistically significantly decreased non-Se-dependent GPx activity. DSF showed also pro-apoptotic activity. NAC alone did not produce any significant changes, besides an increase of GSH t level, in any of the variables measured. However, pre-treatment of cells with NAC ameliorated DSF-induced changes. NAC pre-treatment restored the viability of DSF-treated cells evaluated by Trypan blue exclusion assay and MTT test, GSSG level, and protein carbonyl content to the control values as well as it reduced pro-apoptotic activity of DSF. The increase of CAT and GR activity was not reversed. Activity of both GPx was significantly increased compared to their values after DSF treatment. In conclusion, oxidative properties are at least partially attributable to the cellular effects of disulfiram and mechanisms induced by NAC pre-treatment may lower or even abolish the observed effects. These observations illustrate the importance of the initial cellular redox state in terms of cell response to disulfiram exposure. ►This report explores biological properties of disulfiram under a condition of modulated intra-cellular GSH level. It shows a protective role of N-acetyl- l-cysteine in V79 cells exposed to disulfiram (in GSH metabolism as well as in changes of antioxidant enzyme activity).