In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

Abstract

Free radicals, particularly reactive oxygen species (ROS), are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI) and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans) under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes.

Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations <i>in Vitro</i> and <i>in Vivo</i>

“…Nitroxyl radicals are durable organic free radicals used as spin labels and redox probes. [13][14][15][16][17][18] The calibration curve was linear up to at least 3 mmol/L of nitroxyl radicals, which is consistent with previous findings by Hyodo et al 17) ; however, the slope of the calibration curve was less than one-fifteenth that for Gd-DTPA (data not shown). This difference in sensitivity may result from differences in the number of unpaired electrons in a molecule, 7 electrons for Gd(III) vs. 1 electron for nitroxyl radicals.…”

NMR relaxation and relaxivity parameters of MRI probes revealed by optimal wavelet signal compression of molecular dynamics simulations

“…In most MRI exams, with only the natural relaxation of the hydrogens of the water it is not possible to obtain clear images of the tissues . Thus, to have a better relaxation of the those nuclei, contrast agents (CAs) are used . The CAs are paramagnetic compounds capable of increasing relaxation times constants T 1 and T 2 of water hydrogens in tissues.…”

Exchange Phenomena in the Electron Paramagnetic Resonance Spectra of the Nitroxyl and Trityl Radicals: Multifunctional Spectroscopy and Imaging of Local Chemical Microenvironment

“…This type of experiment has been used to assess tissue redox properties in living animals. Both nitroxide reduction rate 101–103 and hydroxylamine oxidation rate 102 measured by OMRI experiments can be used to map reducing and oxidizing capacities in living subjects, correspondingly. In addition to redox measurements, spatially resolved kinetics measurements of EPR signal intensity provided by OMRI can be used to map the rates of the biradical disulfide, e.g., R 2 SSR 2 , reaction with GSH.…”