Ni2+ enhances Fe2+/peroxide-induced oxidation of arachidonic acid and formation of geno/cytotoxic 4-hydroxynonenal: a possible contributory mechanism in nickel toxicity and allergenicity.
Ni(2+), a toxic, carcinogenic and allergenic agent, affected both the kinetic and chemical courses of the Fe(2+)-induced oxidation of arachidonic acid (AA) in 0.05 M phosphate buffer (pH 7.4) and at 37 degrees C. At 10 microM concentration, Ni(2+) decreased the rate of oxidation of peroxide-free AA (200 microM) promoted by 50 microM Fe(2+), as determined by measurement of thiobarbituric acid reactive species (TBARS) and 1H NMR analysis. However, in the presence of low levels of peroxides (e.g. 2%), Ni(2+) exerted a significant stimulatory effect on Fe(2+)-induced AA oxidation and TBARS formation. 1H NMR analysis showed that Ni(2+) (10 microM) enhanced formation of genotoxic alkenals including 4-hydroxy-2-nonenal (4-HNE, GC/MS evidence) by Fe(2+)-promoted degradation of both AA and 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) methyl esters. The observed stimulatory effects of Ni(2+) on peroxide breakdown and cytotoxic aldehyde formation provide an attractive explanation to the enhanced sensitization capacity of nickel in inflammatory states compared to normal states.
Manini
Paola
P
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126, Naples, Italy.
Napolitano
Alessandra
A
Camera
Emanuela
E
Caserta
Teresa
T
Picardo
Mauro
M
Palumbo
Anna
A
d'Ischia
Marco
M
D000447:Aldehydes / Q000138:chemical synthesis*; D016718:Arachidonic Acid / Q000737:chemistry*; D002413:Cations, Divalent; D008401:Gas Chromatography-Mass Spectrometry; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D015289:Leukotrienes / Q000737:chemistry; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009532:Nickel / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000447:Aldehydes; D002413:Cations, Divalent; D015289:Leukotrienes; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D009532:Nickel; D007501:Iron; C027576:4-hydroxy-2-nonenal