Cyanide and sodium azide intoxication.
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An electron microscopic study was carried out to examine the quality of ultrastructural preservation of parenchymatous and mesenchymatous tissues and isolated cells fixed in glutaraldehyde with sodium azide (NaN3) as an additive. The dense tissues fixed with conventional glutaraldehyde containing calcium chloride demonstrated only a narrow zone of good tissue preservation on the surface of the specimens. Addition of azide at a concentration of 0.1% greatly improved the cellular preservation in the deeper region of tissues, in particular with respect to the mitochondrial morphology. There was no adverse effect on other cell organelles. The improvement in mitochondrial preservation and the enhancement of penetration of the fixative is presumably due to selective and instantaneous inhibition of mitochondrial metabolic activity by the azide, thus retarding anoxic degenerative effects on cellular structures until permanent fixation is completed by the comparatively slow-acting aldehyde. However, the addition of azide offers no significant improvement in the ultrastructural preservation of isolated lymphocytes and liver cells, or fibroblasts maintained in culture.
The high-pressure behavior of nitrogen in NaN(3) was studied to 160 GPa at 120-3300 K using Raman spectroscopy, electrical conductivity, laser heating, and shear deformation methods. Nitrogen in sodium azide is in a molecularlike form; azide ions N(3-) are straight chains of three atoms linked with covalent bonds and weakly interact with each other. By application of high pressures we strongly increased interaction between ions. We found that at pressures above 19 GPa a new phase appeared, indicating a strong coupling between the azide ions. Another transformation occurs at about 50 GPa, accompanied by the appearance of new Raman peaks and a darkening of the sample. With increasing pressure, the sample becomes completely opaque above 120 GPa, and the azide molecular vibron disappears, evidencing completion of the transformation to a nonmolecular nitrogen state with amorphouslike structure which crystallizes after laser heating up to 3300 K. Laser heating and the application of shear stress accelerates the transformation and causes the transformations to occur at lower pressures. These changes can be interpreted in terms of a transformation of the azide ions to larger nitrogen clusters and then polymeric nitrogen net. The polymeric forms can be preserved on decompression in the diamond anvil cell but transform back to the starting azide and other new phases under ambient conditions.
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This study was conducted to compare the effectiveness and efficiency of sodium azide tNaN3) and ethyl methanesulfonate (EMS) for inducing somatic mutations at the yg2 locus in maize seeds of two different metabolic states and cell populations. Dormant or presoaked (72 h at 20 degrees C) seeds heterozygous for yg2 locus were treated with different concentrations of either EMS or NaN3. The cell populations with respect to the percentage of cells in G1, S, G2, and M were also determined for seeds of the two metabolic states. Dormant seeds possessed a higher percentage of cells in G1 and the presoaked seeds a higher percentage of cells in S, G2, and M. The frequency of yg2 sectors in leaves 4 and 5 increased with increasing concentration of both mutagens in both dormant and presoaked seeds. Both mutagens were more effective and efficient in the presoaked seeds. NaN3 was more effective than EMS in terms of number of sectors induced per unit of dose. However, EMS was more efficient as determined by sectors induced per unit of seedling injury and clearly had the ability to induce much higher sector frequencies (more than 10 times greater) than NaN3. The low ability of NaN3 (compared to EMS) to induce mutant sectors may be related to the cells not being treated at the optimum time during the cell cycle, but it is more likely due to its low effectiveness for inducing chromosome aberrations.
A reduction in the activity of cytochrome oxidase, a respiratory chain enzyme, has been recently identified in mitochondria from blood platelets and postmortem brain tissue from Alzheimer's disease (AD) patients. We have developed an animal model of this deficit in rats by chronic subcutaneous infusion of sodium azide, a selective inhibitor of cytochrome oxidase, delivered via Alzet 2ML4 osmotic minipumps. In previous work, azide-treated rats were impaired in an appetitively motivated spatial learning task, the radial arm maze. In the present investigation, we tested male Sprague-Dawley rats (350-400 g), which were tonically infused with azide or saline, on an aversively motivated spatial task, the Morris water maze. Azide-treated rats were impaired on both acquisition and retention of this task, without showing evidence of a motor impairment. Thus, the present results are consistent with previous findings showing that chronic azide treatment produces a learning and memory deficit. These findings strengthen the hypothesis that azide treatment in rats produces a useful animal model of some aspects of AD.
It has been established that granulocytes generate superoxide (O-2) as well as hydrogen peroxide (H2O2) during phagocytosis. The chemiluminescence (CL) generated by phagocytes appears dependent on these oxygen radicals (or). however, recent studies suggest that oxygen molecules, including singlet oxygen (1O2) or hydroxyl radicals (OH-), may also be generated during phagocytosis and contribute to CL. We have tested this possibility by studying human granulocyte CL in the presence of 0.1 mM sodium azide, a known inhibitor of myeloperoxidase and catalase and a scavenger of 1O2. The effects of azide on CL were correlated with the effects of this compound on hexose monophosphate shunt (hmps) activity, nitroblue tetrazolium (NBT) dye reduction, formate oxidation, and cytochrome c reduction. CL generated by granulocytes during the phagocytosis of zymosan particles was markedly impaired by azide (24% to 47% of control values). On the other hand, phenomena dependent in part on the presence of O2 radicals, i.e., reduction of NBT dye and cytochrome c, were not impaired by the presence of azide. As would be expected, inhibition of catalase by azide virtually abolished the oxidation of formate, but the burst in HMPS activity associated with phagocytosis was augmented further. The latter observation indicated that azide did not impair generation of H2O2 but increased the relative amount detoxified via the HMPS. The experiment provides evidence that radicals other than O-2 and H2O2 are generated during phagocytosis and that these radicals are major contributors to the CL phenomenon.
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