Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line.
OBJECTIVE
Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. The aim was to evaluate whether its two opposed effects on lipid peroxidation reported in the literature may be dependent on schedule and doses used.


METHODS
Chang liver cells, a line derived from normal human liver, were grown in media containing either no steroids (control) or DHEA at concentrations ranging from 0.1 micromol/l to 50 micromol/l. At specific times, cultures were halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mmol/l), at which time cell viability (by trypan blue staining and lactate dehydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBARS) concentration (spectrophotometrical assay) were evaluated.


RESULTS
At concentrations ranging from 0.1 micromol/l to 1 micromol/l, DHEA protects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 micromol/l; at higher concentrations (50 micromol/l) a pro-oxidant/cytotoxic effect of DHEA appears.


CONCLUSIONS
DHEA exhibits two opposed effects on lipid peroxidation; depending on its concentration it acts either to limit or to induce oxidative stress. The threshold concentration at which the pro-oxidant activity of DHEA prevails is not far in excess of that having an antioxidant effect. Either effect of DHEA on lipid peroxidation is only evident after a 'lag-phase'.
Gallo
M
M
Department of Clinical Pathophysiology, University of Turin, Via Genova 3, 10126 Turin, Italy.
Aragno
M
M
Gatto
V
V
Tamagno
E
E
Brignardello
E
E
Manti
R
R
Danni
O
O
Boccuzzi
G
G
D001555:Benzene Derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004847:Epithelial Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014343:Trypan Blue
D001555:Benzene Derivatives; D003470:Culture Media; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D003687:Dehydroepiandrosterone; C015763:cumene; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue