The impact of nitrite and antioxidants on ultraviolet-A-induced cell death of human skin fibroblasts.
Nitrite (NO(2)(-)) occurs ubiquitously in biological fluids such as blood and sweat. Ultraviolet A-induced nitric oxide formation via decomposition of cutaneous nitrite, accompanied by the production of reactive oxygen (ROS) or nitrogen species (RNS), represents an important source for NO in human skin physiology. Examining the impact of nitrite and the antioxidants glutathione (GSH), Trolox (TRL), and ascorbic acid (ASC) on UVA-induced toxicity of human skin fibroblasts (FB) we found that NO(2)(-) concentration-dependently enhances the susceptibility of FB to the toxic effects of UVA by a mechanism comprising enhanced induction of lipid peroxidation. While ASC completely protects FB cultures from UVA/NO(2)(-)-induced cell damage, GSH or TRL excessively enhances UVA/NO(2)(-)-induced cell death by a mechanism comprising nitrite concentration-dependent TRL radical formation or GSH-derived oxidative stress. Simultaneously, in the presence of GSH or TRL the mode of UVA/NO(2)(-)-induced cell death changes from apoptosis to necrosis. In summary, during photodecomposition of nitrite, ROS or RNS formation may act as strong toxic insults. Although inhibition of oxidative stress by NO and other antioxidants represents a successful strategy for protection from UVA/NO(2)(-)-induced injuries, GSH and TRL may nitrite-dependently aggravate the injurious impact by TRL or GSH radical formation, respectively.
Department of Plastic and Reconstructive Surgery, Hand Surgery, and Burn Center, University Hospital of the RWTH-Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.
Christian
C
Opländer
Miriam M
MM
Cortese
Hans-Gert
HG
Korth
Michael
M
Kirsch
Csaba
C
Mahotka
Wiebke
W
Wetzel
Norbert
N
Pallua
Christoph V
CV
Suschek
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D005347:Fibroblasts; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D012867:Skin / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D009573:Nitrites; D009569:Nitric Oxide; D005978:Glutathione; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid