Reduced glutathione diesters as antidotes to chemical toxicity and oxidative stress
To investigate the antidote effects of reduced glutathione diesters to chemical toxicity and oxidative stress in vitro and the pharmacokinetics of reduced glutathione diester metabolism in vivo.
Reduced glutathione (GSH) is a cellular antioxidant that is depleted in toxicity associated with exposure to noxious chemical agents, oxidizing agents and linked to some disease mechanisms. GSH diester prodrug is the preferred method for supplementing cellular GSH to prevent toxicity. It was a markedly better agent for the delivery of GSH into cells than GSH monoester, and it had potent antidote activity in vitro to toxicity induced by chemicals (alkylating agents, peroxides, toxic quinones).
Contributions from the GGG Group
Study of the cell dleivery of GSH by unesterified, mono-esterified and di-esterified glutathione derivatives
- Minhas, H.M. and Thornalley, P.J. (1995) Comparison of the delivery of reduced glutathione into reduced glutathione into P388D1 cells by reduced glutathione and its mono- and di-ethyl ester derivatives. Biochem. Pharmacol. 49, 1475-1482.
Quantitative pharmacology of GSH esters as antidotes to chemical toxicity
- Minhas, H.S. and Thornalley, P.J. (1996) Reduced glutathione esters - antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1-chloro-2,4-dinitrobenzene and menadione in murine P388D1 macrophages in vitro. J. Biochem. Toxicol. 10, 245-250.