Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.
The protective effects of selected members from a series of caffeic acid esters and flavonoids were tested in various toxicity paradigms using U937 cells, previously shown to be sensitive to either iron chelators or bona fide radical scavengers or to both classes of compounds. It was found that all the protective polyphenols were active at very low concentrations and that their effects were observed only under those conditions in which iron chelators also afforded protection. Consistently, active polyphenolic compounds, unlike the inactive ones, effectively chelated iron in an in vitro system. It follows that, at least under the experimental conditions utilized in the present study, the most prominent activity of these polyphenolic compounds resides in their ability to chelate iron. Further studies revealed that the protective effects afforded by the caffeic acid esters and flavonoids were largely mediated by the catechol moiety and that the relative biological potency of these compounds was a direct function of their lipophilicity.
Sestili
Piero
P
Istituto di Farmacologia e Farmacognosia, Via S. Chiara 27, 61029 Università di Urbino, Urbino, Italy.
Diamantini
Giuseppe
G
Bedini
Annalida
A
Cerioni
Liana
L
Tommasini
Ilaria
I
Tarzia
Giorgio
G
Cantoni
Orazio
O
D002109:Caffeic Acids / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007501:Iron / Q000378:metabolism*; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D019800:Phenol / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology; D013053:Spectrophotometry; D020298:U937 Cells; D014466:Ultraviolet Rays; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D002109:Caffeic Acids; D002396:Catechols; D002614:Chelating Agents; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D019800:Phenol; D004247:DNA; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007501:Iron; D010100:Oxygen; C040048:caffeic acid