Target Molecules for Reactive Free Radical Metabolites of Aromatic Amines

• Author / Creator

  NARWALEY, MALYAJ

• Aromatic amines during peroxidase metabolism produce N-centered cationic radicals and phenyl radicals as reactive intermediates. The latter also induce protein oxidation. These findings are associated with drug induced agranulocytosis. However, other biomolecular targets of these metabolites are unknown. We tested the reactivity of aromatic amines and congeners with selected poly-unsaturated fatty acids (PUFA) and glutathione (GSH) in the presence of horseradish peroxidase (HRP)/H2O2 by Oxygen electrode, Electron spin resonance (ESR), HPLC and immunospin trapping. Our results show that aromatic amines generating phenyl radical metabolites in presence of HRP/H2O2 oxidise PUFA to form lipid peroxides but do not oxidise GSH. Aromatic amines which do not form detectable phenyl radical oxidized only GSH. Furthermore, ESR and gel-electrophoresis studies showed that PUFAs are target for phenyl radical metabolite and scavenge them, and prevent the protein oxidation induced by phenyl radical. In conclusion, these results suggest a possible mechanism for aromatic amine induced agranulocytosis.

• Subjects / Keywords

  • Poly-unsaturated fatty acids
  • Myeloperoxidase
  • Oxidative stress
  • Glutathione
  • Aromatic amine
  • Agranulocytosis
  • Idiosyncratic Drug reaction
  • Free radical metabolites

• Graduation date

  Fall 2011

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3R394

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.