Selenitetriglicerydes affect CYP1A1 and QR activity by involvement of reactive oxygen species and Nrf2 transcription factor.
Selenitetriglycerides are a group of compounds that contain selenium (Se) (IV). In this paper, we present the results of examinations of three structurally-related selenitetriglicerydes that contain various Se concentrations: 2%, 5% and 7% Selol. The present study concentrates on the effect of Selol on phase 1 and 2 enzyme activity and the implications of free radicals and the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in the activity of this compound. The cytotoxic and cytostatic activities of the three kinds of Selol were evaluated; however, the cytotoxic effect was observed only for 7% Selol. Our results show that 2% Selol acts as a monofunctional inducer of phase 2 enzyme activity, and the induction is mediated by the Nrf2 transcription factor. Selol 7% acts in an opposite manner and induces phase 1 with simultaneous inhibition of phase 2 enzyme activity. The differential effect can be associated with the increase in Se content, leading to a change in the structure of the compound.
National Medicines Institute, Chełmska 30/34, PL 00-725 Warszawa, Poland. misiewicz@il.waw.pl
Piotr
P
Suchocki
Irena
I
Misiewicz-Krzemińska
Katarzyna
K
Skupińska
Katarzyna
K
Niedźwiecka
Katarzyna
K
Lubelska
Zbigniew
Z
Fijałek
Teresa
T
Kasprzycka-Guttman
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000032:analysis / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012643:Selenium / Q000032:analysis; D018038:Sodium Selenite / Q000494:pharmacology*; D014280:Triglycerides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D014280:Triglycerides; D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); D012643:Selenium; D018038:Sodium Selenite