Free radicals as potential mediators of metal-allergy : Ni2+- and Co2+-mediated free radical generation

• Published in: European journal of pharmaceutical sciences 1998-10, Vol.6 (4), p.279-286
• Main Authors: VAN DEN BROEKE, L. T, GRÄSLUND, A, NILSSON, J. L. G, WAHLBERG, J. E, SCHEYNIUS, A, KARLBERG, A.-T
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Adult; Ascorbic Acid - metabolism; Biological and medical sciences; Carnosine - pharmacology; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Cobalt - toxicity; Cysteine - pharmacology; Dermatitis, Allergic Contact - physiopathology; Electron Spin Resonance Spectroscopy; Female; Free Radical Scavengers - pharmacology; Free Radicals - analysis; Glutathione - pharmacology; Histidine - pharmacology; Humans; Hydrogen Peroxide - chemistry; Medical sciences; Medicin och hälsovetenskap; Metals and various inorganic compounds; Middle Aged; Monocytes - drug effects; Monocytes - metabolism; Nickel - toxicity; Toxicology
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(97)10024-0

The generation of free radicals by Ni(2+) and Co(2+) was studied at physiological pH in H(2)O(2)-containing solutions in the absence and presence of various radical-mediating ligands and in human peripheral blood mononuclear cell (PBMC) cultures. With ESR spectroscopy, free radical species were identified and quantitated by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Co(2+) generated hydroxyl radicals from H(2)O(2) in PBS solutions containing glutathione (GSH) or histidine (His). Omission of GSH or His from the reaction mixture significantly reduced the ESR-signal, indicating the importance of metal-chelation in free radical generation. Carnosine did not significantly enhance the reactivity of Co(2+) toward H(2)O(2), whereas cysteine (Cys) and N-acetylcysteine (NAC) suppressed free radical generation. Under identical reaction conditions, Ni(2+) was markedly less reactive toward H(2)O(2) in comparison with Co(2+). GSH, His, Cys and NAC did not enhance free radical generation of Ni(2+) from H(2)O(2). However, in the presence of carnosine weak but significantly enhanced ESR intensities were found. Incubation of PBMC cultures from healthy subjects with Co(2+) (10-50 microM) yielded the DMPO-.OH adduct, suggesting Co(2+)-mediated hydroxyl radical generation. In contrast, incubation of PBMC cultures with Ni(2+) (10-50 microM) did not produce a detectable ESR-signal. Ascorbic acid efficiently inhibited Co(2+)-mediated free radical generation in PBS solutions and PBMC cultures. The observed difference in free radical generating capacity between Ni(2+) and Co(2+) is of interest with respect to the absence of cross-reactivity between the two metal-ions in experimental allergic contact dermatitis.