Inhibition of iron toxicity in rat hepatocyte culture by natural phenolic compounds

Iron supplementation of adult rat hepatocyte culture induced a cytotoxic effect as shown by an increase of lipid peroxidation. The antioxidant activity of some natural phenolic compounds from olive oil (caffeic acid, oleuropein, tyrosol and hydroxytyrosol) has been investigated on this iron-loaded hepatocyte culture model. These compounds greatly reduced malondialdehyde production which was used as a marker for iron-induced lipid peroxidation. This reduction was concentration-dependent of phenolic compound (in the range of 20-100 mum). Moreover, it was not significantly different from one tested compound to another. To clarify the antioxidant mechanism of these compounds, their free radical scavenging activity has been tested in a cell-free experimental model using spin trapping-electron paramagnetic resonance spectroscopy. The four tested compounds were able to scavenge hydroxyl and lipid radicals. They exhibited various efficiency towards hydroxyl radical whereas they presented the same order of reactivity towards lipid radicals. Moreover, only caffeic acid and oleuropein could scavenge Superoxide anion. Therefore, the reactivity of the phenolic compounds towards these reactive oxygen species provided an insight into their antioxidant activity in iron-loaded hepatocyte culture. These compounds could probably interfere with the chain-propagating steps of the lipid peroxidation induced by iron in hepatocytes, which resulted in an inhibition of toxicity.