Molecular Probes for Evaluation of Oxidative Stress by In Vivo EPR Spectroscopy and Imaging: State-of-the-Art and Limitations

Abstract

Oxidative stress, defined as a misbalance between the production of reactive oxygen species and the antioxidant defenses of the cell, appears as a critical factor either in the onset or in the etiology of many pathological conditions. Several methods of detection exist. However, they usually rely on ex vivo evaluation or reports on the status of living tissues only up to a few millimeters in depth, while a whole-body, real-time, non-invasive monitoring technique is required for early diagnosis or as an aid to therapy (to monitor the action of a drug). Methods based on electron paramagnetic resonance (EPR), in association with molecular probes based on aminoxyl radicals (nitroxides) or hydroxylamines especially, have emerged as very promising to meet these standards. The principles involve monitoring the rate of decrease or increase of the EPR signal in vivo after injection of the nitroxide or the hydroxylamine probe, respectively, in a pathological versus a control situation. There have been many successful applications in various rodent models. However, current limitations lie in both the field of the technical development of the spectrometers and the molecular probes. The scope of this review will mainly focus on the latter.

2-Butyl-2-tert-butyl-5,5-diethylpyrrolidine-1-oxyls: Synthesis and Properties

“…109. 4 ), 2.64 (ddd, J d1 = 5.9 Hz, J d2 = 10.0 Hz, J d3 = 4.7 Hz, 1H), 3.47 (dd, J d1 = 10.6 Hz, J d2 = 6.8 Hz, 1H), 3.67 (dd, J d1 = 10.6 Hz, J d2 = 6.8 Hz, 1H). 13 C{ 1 H} NMR (150 MHz, CDCl 3 , δ): 8.…”

“…Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research [1][2][3][4][5][6]. Modern trends in these research fields, such as in-cell electron paramagnetic resonance (EPR)/pulsed electron-electron double resonance (PELDOR) experiments [7,8] and in vivo NMR and EPR imaging [9,10], require stable paramagnetic agents that can retain the radical center in live cells or tissues long enough for the measurements.…”

Orally Administered Activated Charcoal as a Medical Countermeasure for Acute Radiation Syndrome in Rats

“…EPR spectra from the samples were recorded on a computerized spectrometer PE-1307 with resonator H011. The power of the microwave source = 40 mW, the modulation frequency = 100 kHz, amplitude = 10 Gauss, and the receiver's constant time τ = 0.3 s. Rate of O2 •− [15] generation in tissue (nmol in 1 g of tissue during 1 min) is linear during 5 min and every 100 s EPR spectra were consecutively unregistered and used for calculation…”

Special Issue: Electron Paramagnetic Resonance

“…Recent achievements in both theory and instrumentation have made EPR central in order to study new interdisciplinary topics. Such achievements are found in the collection of papers from the Special Issue, devoted to EPR, with contributions in technical improvement [1,2], theory in physics [3], biology [2,4,5], and biochemistry [6]. This issue is articulated around three original articles and three specific reviews.…”

“…Using both the continuous and pulse waves, they showed the improvement of using EPR, compared to other technics, to study the pH-induced functional phase space. Fabien Peyrot and Nikola Babic [5] presented a review on EPR spectroscopy and imaging of evaluation of oxidative stress in vivo. They presented a recent achievement, state of the art, as well as the limitations in the field.…”