Enhanced UV-mediated free radical generation; DNA and mitochondrial damage caused by retinol supplementation.
Retinoid supplementation has been therapeutically used against various human disorders. We and others have demonstrated that retinol treatment causes free radical generation and increased iron uptake, iron storage and oxidative damage, both in vitro and in vivo. Here, we investigate the possible synergistic effect of retinol on UV-mediated free radical generation, oxidative damage to biomolecules and decreased cellular viability in primary cultured mammalian cells. Retinol treatment (7 microM) resulted in a threefold increase in UV-mediated free radical generation and a 40%, increase in lipoperoxidation. DNA fragmentation and mitochondrial oxidative damage also increased significantly in retinol-supplemented UV-irradiated cultured cells as compared to UV-irradiated control cells, which were only treated with the solvent used to deliver the retinol (0.1% ethanol). All measurements were restored to control values when an iron chelator, 1,10-phenanthroline (100 microM), or an OH* scavenger, mannitol (1 mM), was co-administrated. Rather than protecting against free radical generation, retinol seems to enhance UV-mediated oxidative damage and decreases cellular viability in cultured cells. We suggest that retinol-enhanced iron uptake and storage and increased reactive oxygen species generated by the Fenton reaction may act synergistically with UV-irradiation in causing oxidative damage to cells.
Klamt
Fábio
F
Departamento de Biologia, Universidade Luterana do Brasil, Cachoeira do Sul, RS, Brazil. fklamt@terra.com.br
Dal-Pizzol
Felipe
F
Bernard
Elena Aida
EA
Moreira
José Cláudio Fonseca
JC
D000466:Alkadienes / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000528:radiation effects; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000528:radiation effects*; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D014801:Vitamin A / Q000633:toxicity*
D000466:Alkadienes; D016166:Free Radical Scavengers; D005609:Free Radicals; D007502:Iron Chelating Agents; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D014801:Vitamin A; D008353:Mannitol; D004247:DNA