The aliphatic isothiocyanates erucin and sulforaphane do not effectively up-regulate NAD(P)H:quinone oxidoreductase (NQO1) in human liver compared with rat.
Isothiocyanate up-regulation of hepatic NAD(P)H:quinone oxidoreductase (NQO1) and glutathione S-transferases (GSTs) is an integral mechanism of their chemoprevention. In this paper, for the first time, the potential of the isothiocyanates erucin and sulforaphane to modulate these enzymes was investigated in two human livers and compared to rat liver. Precision-cut liver slices were incubated with erucin or sulforaphane (1-50 microM). Both isothiocyanates elevated NQO1 activity in rat slices that was paralleled by a fourfold rise in protein levels. No change in activity was noted in human slices, and only a weak rise in protein levels, < 10% of that in rat, was observed in only one of the human livers, whereas the other was refractive. GST activity, assessed with three substrates, was elevated in rat slices treated with either isothiocyanate, and was accompanied by a rise in GSTalpha and GSTmicro, but not GSTpi, protein levels. A rise in activity and in GSTalpha and GSTmu protein levels was also noted in one of the human livers. It appears that erucin and sulforaphane elevate GST expression in isoform-specific manner in both rat and human liver, whereas NQO1 is inducible by these compounds only in rat liver and very poorly in human liver.
Hanlon
Natalya
N
Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Poynton
Charlotte L
CL
Coldham
Nick
N
Sauer
Maurice J
MJ
Ioannides
Costas
C
D000328:Adult; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013440:Sulfides / Q000494:pharmacology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D015854:Up-Regulation
D017879:Isothiocyanates; D013440:Sulfides; D013454:Sulfoxides; D013861:Thiocyanates; C073539:erucin; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C507703:NQO1 protein, rat; D005982:Glutathione Transferase; C016766:sulforaphane