Induction of epoxide hydrolase and glucuronosyl transferase by isothiocyanates and intact glucosinolates in precision-cut rat liver slices: importance of side-chain substituent and chirality.
The potential of three isothiocyanates, namely R,S-sulforaphane, erucin and phenethyl isothiocyanate, of two naturally occurring glucosinolates, namely glucoerucin and glucoraphanin, and of the enantiomers of sulforaphane to modulate glucuronosyl transferase and epoxide hydrolase, two major carcinogen-metabolising enzyme systems, was investigated in precision-cut rat liver slices. Following exposure of the slices to the isothiocyanates (0-25 μM), erucin and phenethyl isothiocyanate, but not R,S-sulforaphane, elevated glucuronosyl transferase and epoxide hydrolase activities and expression, determined immunologically. Of the two enantiomers of sulforaphane, the R-enantiomer enhanced, whereas the S-enantiomer impaired, glucuronosyl transferase activity and only the former increased protein expression; furthermore, R-sulforaphane was more effective than the S-enantiomer in up-regulating microsomal epoxide hydrolase. When precision-cut rat liver slices were exposed to the same concentrations of glucoerucin and glucoraphanin, both glucosinolates caused a marked increase in the activity and expression of the microsomal epoxide hydrolase but had no effect on glucuronosyl transferase activity. It may be inferred that the ability of isothiocyanates to enhance hepatic microsomal epoxide hydrolase and glucuronosyl transferase activities is dependent on the nature of the side chain. Moreover, in the case of sulforaphane, the naturally occurring R-enantiomer increased both activities, whereas, in contrast, activities were impaired in the case of the S-enantiomer. Finally, intact glucosinolates are potent inducers of epoxide hydrolase and can thus contribute directly to the chemopreventive potential associated with cruciferous vegetable consumption.
Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Ahmad Faizal
AF
Abdull Razis
Manuela
M
Bagatta
Gina Rosalinda
GR
De Nicola
Renato
R
Iori
Costas
C
Ioannides
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004851:Epoxide Hydrolases / Q000096:biosynthesis / Q000187:drug effects*; D005947:Glucose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D005961:Glucosinolates / Q000737:chemistry / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000187:drug effects*; D007096:Imidoesters / Q000737:chemistry / Q000494:pharmacology; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010091:Oximes; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D005961:Glucosinolates; D007096:Imidoesters; D017879:Isothiocyanates; D010091:Oximes; D013440:Sulfides; D013454:Sulfoxides; D013861:Thiocyanates; C005441:phenylisothiocyanate; C119493:glucoerucin; C073539:erucin; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases; C016766:sulforaphane; D005947:Glucose; C119494:glucoraphanin