THE PHARMACOLOGY AND TOXICOLOGY OF POLYPHENOLIC-GLUTATHIONE CONJUGATES

Polyphenolic-glutathione (GSH) conjugates and their metabolites retain the electrophilic and redox properties of the parent polyphenol. Inde ed, the reactivity of the thioether metabolites frequently exceeds tha t of the parent polyphenol. Although the active transport of polypheno lic-GSH conjugates out of the cell in which they are formed will limit their potential toxicity to those cells, once within the circulation they can be transported to tissues that are capable of accumulating th ese metabolites. There are interesting physiological similarities betw een the organs that are known to be susceptible to polyphenolic-GSH co njugate-mediated toxicity. In addition, the frequent localization of g amma-glutamyl transpeptidase to cells separating the circulation from a second fluid-filled compartment coincides with tissues that are susc eptible either to polyphenolic-GSH conjugate-induced toxicity or to qu inone and reactive oxygen species-induced toxicity. Polyphenolic-GSH c onjugates therefore contribute to the nephrotoxicity, nephrocarcinogen icity, and neurotoxicity of a variety of polyphenols.