PMID- 12667605 OWN - NLM STAT- MEDLINE DCOM- 20031016 LR - 20190610 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1621 IP - 1 DP - 2003 Apr 7 TI - 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. PG - 9-16 AB - 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. FAU - Manini, Paola AU - Manini P AD - Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126, Naples, Italy. FAU - Napolitano, Alessandra AU - Napolitano A FAU - Camera, Emanuela AU - Camera E FAU - Caserta, Teresa AU - Caserta T FAU - Picardo, Mauro AU - Picardo M FAU - Palumbo, Anna AU - Palumbo A FAU - d'Ischia, Marco AU - d'Ischia M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Aldehydes) RN - 0 (Cations, Divalent) RN - 0 (Leukotrienes) RN - 0 (Lipid Peroxides) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 27YG812J1I (Arachidonic Acid) RN - 67675-14-3 (15-hydroperoxy-5,8,11,13-eicosatetraenoic acid) RN - 7OV03QG267 (Nickel) RN - E1UOL152H7 (Iron) RN - K1CVM13F96 (4-hydroxy-2-nonenal) SB - IM MH - Aldehydes/*chemical synthesis MH - Arachidonic Acid/*chemistry MH - Cations, Divalent MH - Gas Chromatography-Mass Spectrometry MH - Iron/*chemistry/pharmacology MH - Leukotrienes/chemistry MH - Lipid Peroxidation MH - Lipid Peroxides/chemistry MH - Magnetic Resonance Spectroscopy MH - Models, Chemical MH - Nickel/*chemistry/pharmacology MH - Oxidation-Reduction/drug effects MH - Thiobarbituric Acid Reactive Substances/analysis EDAT- 2003/04/02 05:00 MHDA- 2003/10/17 05:00 CRDT- 2003/04/02 05:00 PHST- 2003/04/02 05:00 [pubmed] PHST- 2003/10/17 05:00 [medline] PHST- 2003/04/02 05:00 [entrez] AID - S0304416503000102 [pii] AID - 10.1016/s0304-4165(03)00010-2 [doi] PST - ppublish SO - Biochim Biophys Acta. 2003 Apr 7;1621(1):9-16. doi: 10.1016/s0304-4165(03)00010-2.