The effect of a nitroxide antioxidant on ischemia-reperfusion injury in the rat in vivo hind limb model.
ABSTRACT Microsurgical procedures such as free tissue transfer or replantations of amputated digits involve an obligatory ischemic period leading to regional tissue oedema, rhabdomyolysis, systemic acidosis, hypercalcemia and multiple organ dysfunction syndrome reflecting ischemia-reperfusion (I/R) injury. Since nitroxide stable radicals act as antioxidants their potential protective effects were tested. Anaesthetized Sabra rats were subjected to regional ischemia of the hind limb for 2 h using a tourniquet. Upon reperfusion rats were injected with 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL). Systemic I/R-induced damage was assessed by sampling blood for differential count, lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels. Regional injury was evaluated by analysing excised muscle samples for oedema (tissue water content) and inflammatory infiltrate (number of cell nuclei in histomorphometric analysis). I/R-induced changes of biomarkers reflecting systemic damage peaked about 8 h following the start of reperfusion and fully disappeared as the biomarkers relaxed to their pre-ischemic values after 24 h. TPL facilitated the recovery of some of these parameters and partially affected release of cellular CPK and LDH. The parameters of I/R-induced regional tissue injury did not demonstrate any recovery and were not inhibited by TPL.
SourceAvailable from: Yoshiaki Uchida[Show abstract] [Hide abstract]
ABSTRACT: An anisotropic and inhomogeneous magnetic interaction (the average spin-spin interaction constant (-)J > 0) was observed in the various liquid crystalline (LC) phases of racemic and nonracemic all-organic radical LC compounds 1a and 1b. We discussed how the LC superstructures induced the magnetic interaction to operate in the LC phases in terms of spin-spin dipole and exchange interactions by means of VT-EPR spectroscopy. The magnitude of the magnetic interaction depended on the type of LC phase, or the superstructure. Furthermore, these radical LC droplets floating on water were commonly attracted to a permanent magnet and moved freely under the influence of this magnet, whereas the crystallized particles of the same compounds never responded to the magnet. The response of the LC droplets to the magnet also varied depending on the type of LC phase, that is, the extent of the magnetic interaction.Journal of the American Chemical Society 07/2010; 132(28):9746-52. DOI:10.1021/ja101930d · 11.44 Impact Factor
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ABSTRACT: Tempol is a redox-cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia.Pharmacology [?] Therapeutics 02/2010; 126(2):119-45. DOI:10.1016/j.pharmthera.2010.01.003 · 7.75 Impact Factor
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ABSTRACT: The pneumatic tourniquet is frequently used for upper and lower limb surgery to reduce bleeding, improve visualisation of important structures and expedite surgical procedures. Despite advances in technology, localised tissue damage secondary to cuff compression, ischaemia-reperfusion injuries and systemic complications still occur. The combination of these problems may affect outcome and contribute to prolonged hospitalisation. Use of the correct pneumatic tourniquet cuff size and a patient-specific cuff pressure with careful control of the duration of inflation may help reduce the incidence of these injuries. The efficacy of ischaemic preconditioning or postconditioning, and experimental treatments such as free radical scavenging, and use of nitric oxide synthetase inhibitors on endothelial dysfunction, systemic neutrophil activation and coagulation reactions needs to be established.European Journal of Anaesthesiology 06/2011; 28(6):404-11. DOI:10.1097/EJA.0b013e328346d5a9 · 2.79 Impact Factor