Modulation of rat hepatic and kidney phase II enzymes by cabbage juices: comparison with the effects of indole-3-carbinol and phenethyl isothiocyanate

Abstract

The effect of raw cabbage and sauerkraut juices on the expression and activity of phase II enzymes, glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in the rat liver and kidney was compared with that of two commercially available products of glucosinolate degradation: indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC). Male Wistar rats were treated by oral administration with cabbage juices, I3C or PEITC for 4, 10 and 30 d. The results showed that juices, particularly sauerkraut juice as with I3C and PEITC, significantly increased GST and NQO1 activities in the rat liver. The only exception was the 30 d time point of feeding with raw cabbage juice. Cabbage juices, I3C and PEITC affected the hepatic GST m to the greatest extent and GST a to a lesser extent. The results of the present study also showed that the treatment of rats with juices and compounds tested caused the translocation of the NF-E2-related transcription factor (Nrf2) active subunit from the cytosol to the nucleus, providing an argument for the involvement of this transcription factor in the induction of GST and NQO1. In contrast to the liver, cabbage juices affected only the renal GST u, while treatment with I3C and PEITC significantly increased the activity of NQO1. Thus, the results of the present study indicate that induction of the key detoxifying enzymes by cabbage juices, particularly sauerkraut, may be responsible for their chemopreventive activity demonstrated by epidemiological studies and in animal models. However, the final effects might be organ or tissue dependent.

The activation of the Nrf2/ARE pathway in HepG2 hepatoma cells by phytochemicals and subsequent modulation of phase II and antioxidant enzyme expression

“…Thus, the results of our present study at mRNA level confirm our earlier observations in in vivo model, showing increased protein levels of these isoforms in rat liver as the result of the administration of these Brassicacae components [10]. Moreover, similarly as in rat liver, phenethyl isothiocyanate was a stronger inducer of the expression of GST isoforms than indole-3-carbinol also in human cells.…”

“…The induction of NQO1 which coincided with increased activity and protein level of NQO1 was observed in our earlier study [10] in rat liver as the result of oral administration of phenethyl isothiocyanate and indole-3-carbinol. In this regard, the results of the present in vitro study confirmed those obtained in the animal model.…”

“…The ability to activate Nrf2-ARE pathway and/or induce phase II enzymes by the breakdown products of glucosinolates such as isothiocyanates and indoles has widely been studied in different systems including HepG2 cells [6,10,14,28]. In contrast, the effect of protocatechuic and tannic acids on phase II enzyme induction was evaluated only in animal models indicating that both compounds have the ability to enhance the activity and protein levels of phase II enzymes in mouse and rat liver [8,10,13].…”

“…In contrast, the effect of protocatechuic and tannic acids on phase II enzyme induction was evaluated only in animal models indicating that both compounds have the ability to enhance the activity and protein levels of phase II enzymes in mouse and rat liver [8,10,13].…”

“…Despite the significant progress in the basic understanding of carcinogenesis, the molecular and cellular targets for the effective chemoprevention by these compounds are poorly characterized. Recent studies have reported the induction of Nrf2 by several chemopreventive compounds including sulforaphane and phenethyl isothiocyanate [10,28]. Moreover, phenolic compounds, especially protocatechuic acid also increased phase II enzymes.…”