Glutathione therapy: from prodrugs to genes

Glutathione (GSH; L-gamma-glutamyl-L-cysteineglycine) is found in almost all mammalian cells, and liver has very high intracellular levels of GSH. It has many cellular functions, such as being a coenzyme, maintaining thiol/disulfide status, protection against toxic compounds and oxidative stress. GSH levels have been reported to be low in a number of pathological conditions; thus methods for increasing GSH levels are desirable. GSH may be increased by supplying its amino acid precursor cysteine, in the form of prodrugs, such as N-acetylcysteine (NAC) and 2-oxothiazolidine-4-carboxylate (OTC). It may also be increased by giving gamma-glutamylcysteine, a dipeptide precursor GSH monoester and GSH diester are effective GSH delivery drugs. Such compounds may be therapeutically useful. Gene therapy may be useful for longer term therapy of GSH deficiency.