The oxyradical-scavenging activity of azelaic acid in biological systems.
We have previously shown that azelaic acid, a C9 dicarboxylic acid, as disodium salt (C(9)2Na) is capable of inhibiting significantly the hydroxylation of aromatic compounds and the peroxidation of arachidonic acid due to reactive hydroxyl radicals (HO.). In this paper we have investigated the ability of C(9)2Na to inhibit the oxyradical induced toxicity towards two tumoral cell lines (Raji and IRE1) and normal human fibroblasts (HF). Oxyradicals were generated either by the addition of polyphenols to the medium, or by direct irradiation of phosphate buffered-saline in which cells were incubated from 15 min prior to incubation in normal medium. The effects of C(9)2Na were compared with those obtained by mannitol (MAN), superoxide dismutase (SOD) and catalase (CAT). C(9)2Na, MAN, SOD and CAT significantly decreased the polyphenol toxicity towards cell lines cultured up to 24 h. After 48 h of incubation the above compounds lost the capability of protecting cells from polyphenol toxicity. This suggests that the toxic role of oxyradicals (O2-., H2O2, HO.) persists for about 24 h and, subsequently other toxic mechanisms must be involved, which are not affected by oxyradical scavengers. SOD and CAT did not show any protective effect on UV induced cytotoxicity, while both C(9)2Na and MAN were capable of reducing significantly the UV damage towards cell lines, even after 48 h incubation. This can be explained by the fact that UV cytotoxicity depends mainly on the generation of HO., that can be "scavenged" by C(9)2Na or MAN, but not by SOD or CAT. C(9)2Na and MAN were not significantly degraded in the period during which they afford protection against HO..
Passi
S
S
San Gallicano Dermatological Institute, Rome, Italy.
Picardo
M
M
Zompetta
C
C
De Luca
C
C
Breathnach
A S
AS
Nazzaro-Porro
M
M
D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D003998:Dicarboxylic Acids; D018492:Dopamine Antagonists; D016166:Free Radical Scavengers; D005609:Free Radicals; D008353:Mannitol; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine; D002374:Catalase; D013482:Superoxide Dismutase; C010038:azelaic acid; D010100:Oxygen; D004298:Dopamine