Effect of amifostine, a radiation-protecting drug, on oxygen concentration in tissue measured by EPR oximetry and imaging.

Effect of amifostine, a radiation-protecting drug, on muscle tissue partial pressure of oxygen was investigated by electron paramagnetic resonance spectroscopy and imaging. When amifostine was administered intraperitoneally or intravenously to mice, the linewidth of the electron paramagnetic resonance spectra of the lithium octa-n-butoxy-substituted naphthalocyanine implanted in the mouse leg muscle decreased. Electron paramagnetic resonance oximetry using a lithium octa-n-butoxy-substituted naphthalocyanine probe and electron paramagnetic resonance oxygen mapping using a triarylmethyl radical paramagnetic probe was useful to quantify pressure of oxygen in the tissues of living mice. The result of electron paramagnetic resonance oximetric imaging showed that administration of amifostine could decrease pressure of oxygen in the muscle and also tumor tissues. This finding suggests that lowering pressure of oxygen in tissues might contribute in part to the radioprotection of amifostine.

Intracellular and extracellular redox environments surrounding redox-sensitive contrast agents under oxidative Atmosphere.

In vivo redox reactions of nitroxyl contrast agents in bile and blood under an oxidative atmosphere were investigated using normal healthy Wistar rats. Differences in intracellular and extracellular volumes in redox environments are discussed. Pharmacokinetic profiles of two nitroxyl contrast agents, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (carbamoyl-PROXYL), 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), in bile and blood were monitored by an electron paramagnetic resonance spectrometer when the rat was breathing 100% O(2) or was subcutaneously administrated 0.2 mmol/kg body weight of ferric citrate. Re-oxidation of hydroxylamines to nitroxyl radicals was caused in bile under 100% O(2) breathing, but not in blood. The administration of ferric citrate caused marked re-oxidation in bile, but a slight reduction in blood. Tissue H(2)O(2) level may partly play a role in the intracellular re-oxidation process. Tissue Fe(3+) concentration can work more effectively for the intracellular re-oxidation of hydroxylamines. The intracellular environment is susceptible to oxidation compared with the extracellular environment under conditions such as 100% O(2) breathing or iron overload.

Enhanced radical-scavenging activity of naturally-oriented artepillin C derivatives.

More than two-fold augmentation in the radical-scavenging activity of artepillin C could be achieved via altering the O-H bond dissociation enthalpy of artepillin C by means of structural modifications.

Nitroxyl radicals: electrochemical redox behaviour and structure-activity relationships.

Comparative study of electrochemical redox behaviour of five different nitroxyl radicals leads to the direct correlation between one-electron redox potentials and group electronegativity of the beta-substituent on the ring. Beta-substituents with an electron-donating effect caused a negative shift in the one-electron oxidation and one-electron reduction potentials of the nitroxyl radicals. In a similar aspect, beta-substituents with an electron-withdrawing effect behaved oppositely.