Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane.
Administration of dietary doses of the isothiocyanate erucin had no effect on rat hepatic cytochrome P450 activity or protein levels, but at higher doses a rise in CYP1A/B1 protein levels was evident. In lung, treatment with erucin, as well as sulforaphane, failed to modulate cytochrome P450 activities but elevated CYP1A/B1 protein levels. In liver, erucin stimulated quinone reductase activity accompanied by a rise in protein. Glutathione S-transferase activity was unaffected, but GSTalpha and GSTmu protein levels increased. In lung, both isothiocyanates increased quinone reductase paralleled by a rise in protein levels; at the higher dose both isothiocyanates elevated moderately GSTalpha levels. Hepatic microsomes converted both isothiocyanates to metabolites that impaired cytochrome P450 activity, which was antagonized by reduced glutathione. It may be concluded that erucin may protect against carcinogens by stimulating the detoxication of quinones but is unlikely to significantly influence reactive intermediate generation through modulation of cytochrome P450 activity.
Hanlon
Natalya
N
Centre of Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
Okpara
Amaka
A
Coldham
Nick
N
Sauer
Maurice J
MJ
Ioannides
Costas
C
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D017879:Isothiocyanates; D013440:Sulfides; D013454:Sulfoxides; D013861:Thiocyanates; D003577:Cytochrome P-450 Enzyme System; C073539:erucin; D005982:Glutathione Transferase; C016766:sulforaphane