This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Dierickx, P J Articles by Alvarez, I Search for Related Content PubMed PubMed Citation Articles by Dierickx, P J Articles by Alvarez, I Social Bookmarking                         What's this?

Glutathione protection against hydrogen peroxide, tert-butyl hydroperoxide and diamide cytotoxicity in rat hepatoma-derived Fa32 cells

G Van Nuffel

I Alvarez

Scientific Institute of Public Health, Afdeling Toxikologie, Wytsmantraat 14, B-1050 Brussel, Belgium

1. 1 Several ozonides, peroxides and aldehydes are formed during ozone therapy, recently introduced in medicine. tert-Butyl hydroperoxide (t-BHP), H₂O₂ and diamide were investigated as model substrate in rat hepatoma-derived Fa32 cells.
   
2. 2 The cytotoxicity was measured by the neutral red uptake inhibition assay after 1 h or 24 h treatment. The relative toxicities were quantified by the determination of the NI₅₀. This is the concentration of test compound required to induce an inhibition of 50% in neutral red uptake as compared to the control cells. All test chemicals were more toxic after 24 h than after 1h.
   
3. 3 The influence of the glutathione (GSH) alteration on the cytotoxicity was measured by treating the cells with 2-oxo-4-thiazolidine carboxylic acid (OTC) or L-buthio-nine sulfoximine (BSO). OTC increased the endogenous GSH content in the cells. BSO pretreatment strongly decreased the NI₅₀ of the three chemicals. OTC pretreatment increased the NI₅₀ of H₂O₂ but not of t-BHP and diamide. This can be explained by the strong GSH-depletion after 1 h by t-BHP and diamide, which contrasted with a weak GSH-depletion by H₂O₂ after the same time period.
   
4. 4 The three test chemicals increased the endogenousGSH content after 24 h. t-BHP and H₂O₂,butnot diamide, increased the total GSH transferase (GST) activity. Several alterations of the GST subunits were observed. Most striking was the increase of class alpha GST subunits, also for diamide.
   
5. 5 SinceH₂O₂ and t-BHP are ozone metabolites thought to be responsible for the therapeutic effects of well-dosed ozone, the results show that Fa32 cells can be used as a valuable alternative model system for studying the effects encountered in human ozone therapy.
   

Key Words: hydrogen peroxide • tert-butyl hydroperoxide • diamide • Fa32 cells • glutathione • protection

Human & Experimental Toxicology, Vol. 18, No. 10, 627-633 (1999)
DOI: 10.1191/096032799678839482


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Zhang, V. Rubio, M. W. Lieberman, and Z.-Z. Shi OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional mechanisms PNAS, September 8, 2009; 106(36): 15356 - 15361. [Abstract] [Full Text] [PDF]

				T. Zeller, K. Li, and G. Klug Expression of the trxC Gene of Rhodobacter capsulatus: Response to Cellular Redox Status Is Mediated by the Transcriptional Regulator OxyR J. Bacteriol., November 1, 2006; 188(21): 7689 - 7695. [Abstract] [Full Text] [PDF]