(18-11-11) Polyphenols and glutathione synthesis regulation

ABSTRACT
Polyphenols in food plants are a versatile group of phytochemicals with many potentially beneficial activities in terms of disease pre- vention. In vitro cell culture experiments have shown that polyphe- nols possess antioxidant properties, and it is thought that these ac- tivities account for disease-preventing effects of diets high in polyphenols. However, polyphenols may be regarded as xenobiotics by animal cells and are to some extent treated as such, ie, they interact with phase I and phase II enzyme systems. We recently showed that dietary plant polyphenols, namely, the flavonoids, modulate expres- sion of an important enzyme in both cellular antioxidant defenses and detoxification of xenobiotics, ie, -y-glutamylcysteine synthetase. This enzyme is rate limiting in the synthesis of the most important endogenous antioxidant in cells, glutathione. We showed in vitro that flavonoids increase expression of -y-glutamylcysteine syn- thetase and, by using a unique transgenic reporter mouse strain, we showed increased expression in vivo, with a concomitant increase in the intracellular glutathione concentrations in muscles. Because glu- tathione is important in redox regulation of transcription factors and enzymes for signal transduction, our results suggest that polyphenol- mediated regulation of glutathione alters cellular processes. Evi- dently, glutathione is important in many diseases, and regulation of intracellular glutathione concentrations may be one mechanism by which diet influences disease development. The aim of this review is to discuss some of the mechanisms involved in the glutathione- mediated, endogenous, cellular antioxidant defense system, how its possible modulation by dietary polyphenols such as flavonoids may influence disease development, and how it can be studied with in vivo imaging.

Source: Am J Clin Nutr 2005;81(suppl):277S? 83S.

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