OxyFile #645

AU  - Dierickx PJ
AU  - Nuffel GV
AU  - Alvarez I

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

AB  - 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. 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 1 h. 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-buthionine 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. The three test chemicals increased 
      the endogenous GSH content after 24 h. t-BHP and H2O2, 
      but not 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. Since H2O2 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.

MH  - tert-Butylhydroperoxide|PD/*TO
MH  - Diamide|PD/*TO
MH  - Glutathione|*ME
MH  - Hydrogen Peroxide|PD/*TO
MH  - Oxidants|*PD
MH  - Protective Agents|*ME
SO  - Hum Exp Toxicol 1999 Oct; 18(10):627-33
DP  - 1999 Oct
TA  - Hum Exp Toxicol
PG  - 627-33
IP  - 10
VI  - 18
UI  - 20025524