Exogenous markers for the characterization of human diseases associated with oxidative stress

Many human conditions, including neurological diseases, atherosclerosis, cancer, diabetic complications and aging, are thought to be associated with oxidative stress (OS). The development of reliable and informative markers for the characterization of OS in humans is thus highly important. Various endogenous markers are known, but their accumulation with increasing OS and with time is not certain, and most of them do not provide information on the type or source of the stress, or on the kinetics of their formation. The aim of the present overview is to present exogenous markers, designed and synthesized by our group, which are sensitive to OS and can identify its presence, the type of reactive oxygen and nitrogen species involved ex vivo, and potential damage incurred by bio-macromolecules, in real time. A microdialysis technique is used in animals for evaluation of OS in vivo. The designed probes are composed of several endogenous subunits, attached together covalently to form molecules that do not exist as such in humans. The subunits include an amino acid (tyrosine), an unsaturated fatty acid (linoleic acid), a nucleic acid (2′-deoxyribose guanosine) and cholesterol, representing the major macromolecules of the body, i.e. proteins, lipids, DNA and sterols, respectively. Incubation of these markers in a biological sample ex vivo, such as blood/serum, urine, saliva, cells or tissues under OS, alters their subunits, which are then analyzed and identified by LC/MS. This review demonstrates the potential of these markers to identify OS in samples taken from humans and animals suffering from, for example, atherosclerosis, hypertension, or Alzheimer's or Parkinson's disease.