Toxicity of nutritionally available selenium compounds in primary and transformed hepatocytes

Markus Weiller, Markus Latta, Matthias Kresse, Rudolf Lucas, Albrecht Wendel

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The essential trace element selenium is also toxic at low doses. Since supplementation of selenium is discussed as cancer prophylaxis, we investigated whether or not bioavailable selenium compounds are selectively toxic on malignant cells by comparing primary and transformed liver cells as to the extent and mode of cell death. Sodium selenite and selenate exclusively induced necrosis in a concentration-dependent manner in all cell types investigated. In primary murine hepatocytes, the EC50 was 20 μM for selenite, 270 μM for selenate, and 30 μM for Se-methionine. In the human carcinoma cell line HepG2, the EC50 for selenite was 40 μM, and for selenate 1.1 mM, whereas Se-methionine was essentially non-toxic up to 10 mM. Similar results were found in murine Hepa1-6 cells. Exposure of primary murine cells to selenate or selenite resulted in increased lipid peroxidation. Toxicity was inhibited by superoxide dismutase plus catalase, indicating an important role for reactive oxygen intermediates. In primary hepatocytes, metabolical depletion of intracellular ATP by the ketohexose tagatose, significantly decreased the cytotoxicity of Se-methionine, while the one of selenite was increased. These data do not provide any in vitro evidence that bioavailable selenium compounds induce preferentially apoptotic cell death or selectively kill transformed hepatocytes.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalToxicology
Volume201
Issue number1-3
DOIs
StatePublished - Sep 1 2004

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Selenium Compounds
Selenic Acid
Selenious Acid
Toxicity
Hepatocytes
Methionine
Poisons
Cell death
Selenium
Sodium Selenite
Cell Death
Trace Elements
Cytotoxicity
Liver
Catalase
Superoxide Dismutase
Adenosine Triphosphate
Cells
Lipid Peroxidation
Oxygen

Keywords

  • EC
  • GPx
  • GSSeH
  • HSe
  • MDA
  • O
  • Se-cysteine
  • Se-methionine
  • glutathione peroxidase
  • hydrogen selenide
  • malondialdehyde
  • median effective concentration
  • seleno persulfide
  • selenocysteine
  • superoxide-anion

ASJC Scopus subject areas

  • Toxicology

Cite this

Toxicity of nutritionally available selenium compounds in primary and transformed hepatocytes. / Weiller, Markus; Latta, Markus; Kresse, Matthias; Lucas, Rudolf; Wendel, Albrecht.

In: Toxicology, Vol. 201, No. 1-3, 01.09.2004, p. 21-30.

Research output: Contribution to journalArticle

Weiller, Markus ; Latta, Markus ; Kresse, Matthias ; Lucas, Rudolf ; Wendel, Albrecht. / Toxicity of nutritionally available selenium compounds in primary and transformed hepatocytes. In: Toxicology. 2004 ; Vol. 201, No. 1-3. pp. 21-30.
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