The natural compound ascorbigen modulates NADPH-quinone oxidoreductase (NQO1) mRNA and enzyme activity levels in cultured liver cells and in laboratory rats.
Ascorbigen (ABG) is a natural compound that represents a breakdown product of the glucosinolates that are present in Brassica vegetables. It is postulated that ABG may have anticarcinogenic activity; however, the underlying molecular and cellular mechanisms are largely unknown. In the present study we investigated the effect of ABG on the mRNA and enzyme activity levels of NADPH-quinone oxidoreductase (NQO1), which is centrally involved in the detoxification of xenobiotics, in cultured liver cells and in rats. The mRNA levels of NQO1 showed an increase of up to 100% in cultured liver cells (HepG2) following incubation with different concentrations of ABG (3-100 micromol/l) compared to control cells. Furthermore, NQO1 activity was elevated (up to 20%) by ABG treatment. The in vitro results were confirmed in rats who received either 5 mg/day ABG or vehicle for 7 days. Significantly higher mRNA (a 90% increase) and enzyme activity levels (a 40% increase) of NQO1 were detected in the liver of ABG-treated rats as compared to control animals. Current data indicate that ABG is a moderate inducer of the phase II enzyme NQO1, both in cultured hepatocytes and in vivo.
Wagner
Anika E
AE
Institute of Human Nutrition and Food Science, Christian Albrechts University, Kiel, Germany.
Hug
Hubert
H
Gössl
Richard
R
Riss
Georges
G
Mussler
Bernd
B
Elste
Volker
V
Rimbach
Gerald
G
Barella
Luca
L
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D007211:Indoles; D012333:RNA, Messenger; C053152:ascorbigen; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase; D001205:Ascorbic Acid