Isozyme- and gender-specific induction of glutathione S-transferases by flavonoids

Most dietary flavonoids have antioxidant activity in vitro however, secondary mechanisms such as the ability to influence gene expression with the consequent modulation of specific enzymatic activities involved in the intracellular response against oxidative stress, are being realized. In the following study, we examined the ability of the flavonoids: flavone, morin, naringenin, (+)-catechin, and quercetin to modulate the activity of glutathione S-transferases (GSTs) mGSTA, mGSTP and mGSTM in hepatic tissues of male and female Swiss Webster mice. Subchronic dietary exposure to morin, naringenin, (+)-catechin, and quercetin (2,500 mg/kg diet for 20 days) did not produce statistically significant changes in GST activity. Conversely, gender-, and isozyme-specific induction of mGSTs were observed in animals fed flavone. A sevenfold increase in total mGST activity was observed in female animals whereas a fourfold increase was observed in male animals. Enzyme specific assays indicate that there were greater increases of both mGSTM (eightfold) and mGSTP (fourfold) activities in females as compared to males (sixfold and twofold, respectively). As testosterone is involved in the regulation of GSTs in mice, castrated males were fed flavone for 5 days (2,500 mg/kg diet). In this case, dietary flavone resulted in similar fourfold increases in total GST activity in inact and castrated animals. Isozyme specific studies indicate that increases could be attributed to an induction of mGSTM and mGSTP.