Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation.

Although it is known that Mediterranean diet plays an important role in maintaining human health, the underlying molecular mechanisms remain largely unknown. The aim of this investigation was to elucidate the potential role of ortho-dihydroxy group containing natural compounds in H2O2-induced DNA damage and apoptosis. For this purpose, the main phenolic alcohols of olive oil, namely hydroxytyrosol and tyrosol, were examined for their ability to protect cultured cells under conditions of oxidative stress. A strong correlation was observed between the ability of hydroxytyrosol to mitigate intracellular labile iron level and the protection offered against H2O2-induced DNA damage and apoptosis. On the other hand, tyrosol, which lacks the ortho-dihydroxy group, was ineffective. Moreover, hydroxytyrosol (but not tyrosol), was able to diminish the late sustained phase of H2O2-induced JNK and p38 phosphorylation. The derangement of intracellular iron homeostasis, following exposure of cells to H2O2, played pivotal role both in the induction of DNA damage and the initiation of apoptotic signaling. The presented results suggest that the protective effects exerted by ortho-dihydroxy group containing dietary compounds against oxidative stress-induced cell damage are linked to their ability to influence changes in the intracellular labile iron homeostasis.

Lipophilic caffeic acid derivatives protect cells against H2O2-Induced DNA damage by chelating intracellular labile iron.

Naturally occurring cinnamic acid derivatives are ubiquitously distributed in the plant kingdom, and it has been proposed that their consumption contributes to the maintenance of human health. However, the molecular mechanisms underlying their health keeping effects remain unknown. In the present investigation, we evaluated the capacity of several cinnamic acid derivatives (trans-cinnamic, p-coumaric, caffeic and ferulic acids, as well as caffeic acid-methyl and -propyl esters) to protect cells from oxidative stress-induced DNA damage. It was observed that effective protection was based on the ability of each compound to (i) reach the intracellular space and (ii) chelate intracellular "labile" iron. These results support the notion that numerous lipophilic iron chelating compounds, present abundantly in plant-derived diet components, may protect cells in conditions of oxidative stress and in this way be important contributors toward maintenance of human health.