Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Objective: Dehydroepiandrosterone (DHEA) is a widely studied steroid hormon e with multi-functional properties. Reports suggest that some of the many a ctivities of DHEA are due to its protective effect against lipid peroxidati on. 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 d oses used. Methods: Chang liver cells, a line derived from normal human liver, were gr own in media containing either no steroids (control) or DHEA at concentrati ons ranging from 0.1 mu mol/l to 50 mu mol/l. At specific times, cultures w ere halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mm ol/l), at which time cell viability (by trypan blue staining and lactate de hydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBA RS) concentration (spectrophotometrical assay) were evaluated. Results: At concentrations ranging from 0.1 mu mol/l to 1 mu mol/l, DHEA pr otects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 mu mol/l at higher concentrations (50 mu mol/l) a pro-oxidant/cytotoxic effect of DHEA appears. Conclusions: DHEA exhibits two opposed effects on lipid peroxidation; depen ding on its concentration it acts either to limit or to induce oxidative st ress. 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'.