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

Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.08.004· OSTI ID:21460227

Grosicka-Maciag, Emilia; Kurpios-Piec, Dagmara ^[1]; Grzela, Tomasz ^[2]; Czeczot, Hanna; Skrzycki, Michal; Szumilo, Maria ^[1]; Rahden-Staron, Iwonna ^[1]

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1. Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Banacha 1 (Poland)
2. Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warszawa, Chalubinskiego 5 (Poland)

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 {mu}M concentration. It was evidenced by a statistically significant increase of both GSH{sub 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{sub 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. -- Research Highlights: {yields}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).

• OSTI ID: 21460227
• Journal Information: Toxicology and Applied Pharmacology, Vol. 248, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.08.004; PII: S0041-008X(10)00277-2; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIOXIDANTS
APOPTOSIS
CYSTEINE
ENZYME ACTIVITY
FIBROBLASTS
GLUTATHIONE
HAMSTERS
METABOLISM
OXIDATION
STRESSES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DRUGS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
RODENTS
SOMATIC CELLS
THIOLS
VERTEBRATES