Reduced glutathione esters—antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and menadione in murine P388D1 macrophages in vitro
✍ Scribed by Minhas, Harjit S. ;Thornalley, Paul J.
- Book ID
- 102876490
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 630 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0887-2082
No coin nor oath required. For personal study only.
✦ Synopsis
Repletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEtJ on the cytotoxicity of hydrogen peroxide, l-chloro-2,4-dinitrobenzene (CDNB), and menadione to P388D1 macrophages in vitro was investigated. The median toxic concentration TC, values of the toxicants were hydrogen peroxide 24 f 2 mM ( N = 19), CDNB 63 f 6 pM ( N = 18), and menadione 30 f 4pM ( N = 22). Reduced glutathione, GSHEt, and GSHEt, were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB-and menadione-mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC,, values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC,, values were GSHEt 23.8 f 4.1 mM ( N = 91, 3.6 f 0.6 mM (N = 111, and 226 f 93 pM ( N = 12); and GSHEt, 20.4 f 1.9 mM (N = 6), 603 2 2 pM ( N = 91, and 7.6 f 2.3 pM (N = 12).
Reduced glutathione ethyl diester was a potent antidote to CDNB-and menadione-induced toxicities but not to hydrogen peroxide-induced toxicity under acute intoxication conditions.