Selenitetriglicerydes affect CYP1A1 and QR activity by involvement of reactive oxygen species and Nrf2 transcription factor

Pharmacol Rep. 2010 Mar-Apr;62(2):352-61. doi: 10.1016/s1734-1140(10)70275-9.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors*
  • Humans
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • NF-E2-Related Factor 2 / analysis
  • NF-E2-Related Factor 2 / physiology*
  • Reactive Oxygen Species / metabolism*
  • Selenium / analysis
  • Sodium Selenite / pharmacology*
  • Triglycerides / pharmacology*

Substances

  • Antineoplastic Agents
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • Triglycerides
  • Cytochrome P-450 CYP1A1
  • NAD(P)H Dehydrogenase (Quinone)
  • Selenium
  • Sodium Selenite