Glutathione in its reduced form (GSH) cannot be used to boost cellular/tissue levels of the anti-oxidant in living organisms, including poultry. The reason is that GSH in the extracellular environment is highly susceptible to oxidation to its oxidized (GSSG, and protein-bound or GS-protein) forms, and is biodegraded by gamma-glutamyl transferases particularly in those tisses with high activity of these enzymes. Instead, since cysteine is the rate-limiting amino acid for GSH synthesis, increasing the supply of this sulphur amino acid or its precursors through enteral or parenteral routes is one of the most effective strategies to enhance GSH levels in living organisms through the synthetic route. However, since cysteine is highly unstable in its reduced (CySH) form and is also toxic at high concentrations, it may not always be practical to use the amino acid as a supplement. Also, cysteine administration is associated with a reduction in tissue GSH consecutive to the production of hydroxyl radicals generated by the autoxidation of CySH into the oxidized form (CySS) of the aminao acid. Hence, the pharmacological use of CySH prodrugs (such as N-acetyl-cysteine (NAC), OTC and PTCA), CySH amino acid precursors (e.g. Methionine) and GSH esters is considered a more suitable choice to restore tissue GSH concentrations (Sen & Packer, 2000; Li et al., 2002; Oz et al., 2005). However, some of these are of limited oral bioavailability and may be toxic (Koch et al., 1994; Reid et al., 1994; Sen, 1997; Sen & Packer, 2000). Also, the tolerance of an organism toward an amino acid supply may be limited (Morand et al., 1997). Notwithstanding, Methionine is one cysteine precursor amino acid that has been successfully used to bolster cellular/tissue GSH levels (Hunter & Grimble, 1997; Morand et al., 1997).
Nutritional interventions involving the use of foods containing SAA-rich proteins have also shown to be preferable as a more natural strategy to bolster tissue glutathione concentrations. In this connection, the use of milk by-products, in particular, dietary supplementation with cyst(e)ine-rich whey proteins, has been shown to enhance cellular/tissue GSH levels (Bounous et al., 1989; Bounous et al., 1991; Bounous & Gold, 1991; Bounous et al., 1993; Kennedy et al., 1995; Zommara et al., 1998; Bounous & Molson, 1999; Lands et al., 1999; Micke et al., 2001; Ha & Zemel, 2003; Kent et al., 2003; Grey et al., 2003).
Also, use of anti-oxidants like vitamin C, vitamin E and some plant phytochemicals has been shown to be effective in bolstering cellular/tissue GSH.
However, I believe the most effective drug is N-acetyl-cysteine. On the other hand, the most effective nutritional product is whey protein (or whey protein concentrate).
Hope this is helpful.
Dr. DMN Mthiyane
North-West University, South Africa