Arachidonic acid (AA) was shown to be toxic to HepG2 cells expressing cytochrome P4502E1 (CYP2E1) because of oxidative stress. The aim of this study was to investigate whether lycopene, a carotenoid with high anti-oxidant capacity, protects HepG2 cells expressing CYP2E1 against AA toxicity. In preliminary experiments, lycopene as well as placebo (vehicle) were not toxic in the three types of cells tested: HepG2 cells, HepG2 cells transfected with pCI-neo (Neo) or pCI-neo/2E1 (2E1). AA produced toxic effects, especially in the 2E1 cells, and caused a remarkable increase in hydrogen peroxide production and lipid peroxidation compared to the Neo and HepG2 cells. Lycopene had a protective effect whereas the placebo did not. This was due, at least in part, to inhibition of hydrogen peroxide production and of the resulting lipid peroxidation, confirming the potent anti-oxidant properties of lycopene and its suitability for clinical studies. (C) 2003 Elsevier Science (USA). All rights reserved.