Ni2+, a toxic, carcinogenic and allergenic agent, affected both the kinetic and chemical courses of the Fe2+-induced oxidation of arachidonic acid (AA) in 0.05 M phosphate buffer (pH 7.4) and at 37 degreesC. At 10 muM concentration, Ni2+ decreased the rate of oxidation of peroxide-free AA (200 muM) promoted by 50 muM Fe2+, as determined by measurement of thiobarbituric acid reactive species (TBARS) and H-1 NMR analysis. However, in the presence of low levels of peroxides (e.g. 2%), Ni2+ exerted a significant stimulatory effect on Fe2+- induced AA oxidation and TBARS formation. H-1 NMR analysis showed that Ni2+ (10 muM) enhanced formation of genotoxic alkenals including 4-hydroxy-2-nonenal (4-HNE, GC/MS evidence) by Fe2+-promoted degradation of both AA and 15-hydroperoxy-5,8,11,13-eicosatetracnoic acid (15-HPETE) methyl esters. The observed stimulatory effects of Ni2+ 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.
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
D'ISCHIA, MARCO
2003
Abstract
Ni2+, a toxic, carcinogenic and allergenic agent, affected both the kinetic and chemical courses of the Fe2+-induced oxidation of arachidonic acid (AA) in 0.05 M phosphate buffer (pH 7.4) and at 37 degreesC. At 10 muM concentration, Ni2+ decreased the rate of oxidation of peroxide-free AA (200 muM) promoted by 50 muM Fe2+, as determined by measurement of thiobarbituric acid reactive species (TBARS) and H-1 NMR analysis. However, in the presence of low levels of peroxides (e.g. 2%), Ni2+ exerted a significant stimulatory effect on Fe2+- induced AA oxidation and TBARS formation. H-1 NMR analysis showed that Ni2+ (10 muM) enhanced formation of genotoxic alkenals including 4-hydroxy-2-nonenal (4-HNE, GC/MS evidence) by Fe2+-promoted degradation of both AA and 15-hydroperoxy-5,8,11,13-eicosatetracnoic acid (15-HPETE) methyl esters. The observed stimulatory effects of Ni2+ 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
