Up-regulation of the CYP1 family in rat and human liver by the aliphatic isothiocyanates erucin and sulforaphane

Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane

“…Both isothiocyanates led to a marked elevation of CYP1A1 and, to a lesser extent, CYP1B1 apoprotein levels, whereas CYP2B was unaffected and CYP3A2 was moderately up-regulated only by sulforaphane. A similar qualitative picture was obtained in liver slices incubated with these isothiocyanates under identical conditions [14]. Despite the marked rise in CYP1A1 expression, no commensurate increase in activity, as exemplified by the O-deethylation of ethoxyresorufin, was observed.…”

“…As erucin is a major metabolite of sulforaphane, at least in rat [41,42], it is conceivable that it contributes to its chemopreventive effects. No major tissue differences between lung and liver slices [14,36] could be discerned in their response to the two isothiocyanates. The most marked effects manifested by sulforaphane and erucin were enhanced quinone reductase and glutathione S-transferase activity, and this mechanism may be largely responsible for the documented chemopreventive effect of isothiocyanates in the lung of animals exposed to polycyclic aromatic hydrocarbons.…”

“…Consequently, we investigated the potential of sulforaphane and erucin (1-isothiocyanato-4-(methylthio)-butane), a structurally related isothiocyanate present in rocket salad, to modulate carcinogen-metabolising enzyme systems in rat lung; it has already been documented that these isothiocyanates modulate these enzyme systems in rat liver [14]. The studies reported here were conducted in vitro utilising precisioncut lung slices [15] The principal advantages of this in vitro system are that it maintains tissue architecture and cell-cell communication, and allows the facile use of a wide range of concentrations of chemicals, that would otherwise necessitate large animal numbers for commensurate in vivo studies [16].…”

The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are weak agonists but potent non-competitive antagonists of the aryl hydrocarbon receptor

“…Incubation of slices with the isothiocyanates (10 µM) for various time periods revealed that in both cases a significant increase in CYP1A1 mRNA required incubation times longer than 6 hours to be achieved ( Figure 6B). Benzo[a]pyrene caused a marked increase in CYP1A1 mRNA levels in rat slices, and this could be antagonised by R,S-sulforaphane and erucin, the former being more effective at the highest concentration examined (Figures 6C) isothiocyanates, both in vivo and in vitro, up-regulated the expression CYP1A2 and CYP1B1 in rat liver, and of CYP1A1 and CYP1B1 in rat lung (Yoxall et al 2005;Hanlon et al 2008bHanlon et al , 2008cHanlon et al , 2009b. Clearly, the increase in the expression of these enzymes represents, at least partly, increased transcription.…”

Isothiocyanates: A Chemical Class of Potential Nutraceuticals

“…In in vivo studies, however, exposure of rats to dietary doses of either sulforaphane or erucin did not result in any changes in CYP1A or CYP2B activities in either liver or lung [33,34]. Extensive studies in precision-cut rat and human liver, and rat lung slices, utilising a wide range of isothiocyanate concentrations, further demonstrated the inability of these compounds to modulate cytochrome P450 activity [35,36]. However, when the same cytochrome P450 enzymes were monitored at the protein level, both isothiocyanates increased CYP1A expression, and the lack of a concomitant increase in activity was demonstrated to be due to the fact that both these compounds are mechanism-based inhibitors [33,34].…”