The chemopreventive potential of dietary glucosinolates

Dietary intake of a glucosinolate-rich Daikon extract (glucoraphasatin and glucoraphenin) elevated rat hepatic dealkylations of methoxy-, ethoxy-, pentoxyresorufin and benzyloxyquinoline, accompanied by increased expression of CYPl and CYP3A2 apoprotein levels. A marked induction of glutathione S- transferase and quinone reductase activities in liver was evident, as well as of glucuronosyl transferase and epoxide hydrolase activities and expression, but only at higher doses. Lung enzymes were not altered by the same treatment. In precision-cut rat liver slices glucoraphasatin caused a marked increase in epoxide hydrolase activity. Addition of myrosinase to form the isothiocyanate led to a marked rise in glutathione S-transferase, quinone reductase and epoxide hydrolase activities and expression. Incubation of precision-cut rat liver slices with intact glucosinolates (glucoerucin and glucoraphanin) enhanced the O-dealkylations of methoxy- and ethoxyresorufin and elevated CYPl apoprotein levels; similar effects were observed in lung slices. Both glucosinolates increased hepatic epoxide hydrolase, glutathione S-transferase and quinone reductase activities. Studies on the temporal induction of carcinogen-metabolising enzyme systems by glucosinolates and isothiocyanates in precision-cut rat liver slices indicated that a six- hour tissue exposure was required for induction of all enzymes to be manifested. The potential of the naturally-occurring R-sulforaphane to up-regulate carcinogen- metabolising enzyme in precision-cut rat liver slices and FAO cells was compared to that of S-sulforaphane; R -sulforaphane was superior in modulating these enzyme systems in both systems. Using the CALUX assay it was established that phenethyl isothiocyanate, erucin and sulforaphane were poor ligands to the Ah receptor. However, they effectively antagonised, III a non-competitive manner, the activation of the receptor by benzo[a]pyrene. Further studies revealed that sulforaphane could prevent and reverse the activation of the Ah receptor by benzo[a]pyrene.EThOS - Electronic Theses Online ServiceGBUnited Kingdo