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Blood Jul 1994Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have...
Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have evaluated transport of Na+ and K+ in erythrocytes of patients with thalassemias as well as in two experimental models that use normal human red blood cells, one for alpha thalassemia (methylhydrazine treatment, alpha thalassemia like) and one for beta thalassemia (phenylhydrazine treatment, beta thalassemia like). With the exception of the Na-K pump, similar alterations in membrane transport were observed in thalassemia and thalassemia-like erythrocytes. These were: increased K-Cl cotransport, Na-Li countertransport and reduced Na-K-Cl cotransport. The Na-K pump was reduced in thalassemia-like cells, whereas it was increased in severe alpha thalassemia and in beta thalassemia cells. The increased K-Cl cotransport activity could be observed in light and dense fractions of beta-thalassemic cells. K-Cl cotransport in thalassemic and thalassemia-like erythrocytes was partially inhibited by [(dihydro-indenyl) oxy] alkanoic acid and completely abolished by dithiothreitol. Thus, oxidative damage represents an important factor in the increased activity of the K-Cl cotransport observed in thalassemias, and of the K+ loss observed in beta-thalassemia erythrocytes.
Topics: Chlorides; Erythrocyte Membrane; Humans; Ion Transport; Monomethylhydrazine; Phenylhydrazines; Potassium; Sodium-Potassium-Exchanging ATPase; Thalassemia
PubMed: 8018927
DOI: No ID Found -
Blood Mar 1992We have previously shown that excess unpaired alpha- and beta-globin chains in severe alpha- and beta-thalassemia interacting with the membrane skeleton induce different...
We have previously shown that excess unpaired alpha- and beta-globin chains in severe alpha- and beta-thalassemia interacting with the membrane skeleton induce different changes in membrane properties of red blood cells (RBCs) in these two phenotypes. We suggest that these differences in membrane material behavior may reflect the specificity of the membrane damage induced by alpha- and beta-globin chains. To further explore this hypothesis, we sought in vitro models that induce similar membrane alterations in normal RBCs. We found that treatment of normal RBCs with phenylhydrazine produced rigid and mechanically unstable membranes in conjunction with selective association of oxidized alpha-globin chains with the membrane skeleton, features characteristic of RBCs in severe beta-thalassemia. Methylhydrazine, in contrast, induced selective association of oxidized beta-globin chains with the membrane skeleton and produced rigid but hyperstable membranes, features that mimicked those of RBCs in severe alpha-thalassemia. These findings suggest that consequences of oxidation induced by globin chains are quite specific in that those agents that cause alpha-globin chain accumulation at the membrane produce rigid but mechanically unstable membranes, whereas membrane accumulation of beta-globin chains results in rigid but mechanically stable membranes. These in vitro experiments lend further support to the hypothesis that membrane-associated alpha- and beta-chains induce oxidative damage to highly specific different skeletal components and that the specificity of this skeletal damage accounts for the differences in material membrane properties of these oxidatively attacked RBCs and perhaps of alpha- and beta-thalassemic RBCs as well.
Topics: Erythrocyte Deformability; Erythrocyte Membrane; Globins; Humans; Methylphenazonium Methosulfate; Monomethylhydrazine; Oxidation-Reduction; Phenylhydrazines; Thalassemia
PubMed: 1547347
DOI: No ID Found -
The Journal of Biological Chemistry Dec 1990Methylhydrazine oxidation promoted by horseradish peroxidase-H2O2 or ferricyanide led to the generation of high yields of methyl radicals and to the formation of...
Methylhydrazine oxidation promoted by horseradish peroxidase-H2O2 or ferricyanide led to the generation of high yields of methyl radicals and to the formation of 7-methylguanine and 8-methylguanine upon interaction with calf thymus DNA. Methyl radicals were identified by spin-trapping experiments with alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone and tert-nitrosobutane. The methylated guanine products were identified in the neutral hydrolysates of treated DNA by high pressure liquid chromatography (HPLC) analysis and spiking with authentic samples. The structure of 8-methylguanine, a product not previously reported in enzymatic systems, was confirmed by HPLC chromatography, UV absorbance, and mass spectrometry. The formation of 8-methylguanine suggests a possible role for carbon-centered radicals as DNA-alkylating agents.
Topics: Alkylation; DNA; Electron Spin Resonance Spectroscopy; Free Radicals; Guanine; Horseradish Peroxidase; Hydrolysis; Mass Spectrometry; Monomethylhydrazine; Oxidation-Reduction; Spectrophotometry, Ultraviolet
PubMed: 2176204
DOI: No ID Found -
The Journal of Biological Chemistry Mar 1990The dissimilatory nitrite reductase, cytochrome cd1, from Pseudomonas aeruginosa (ATCC 19429) was irreversibly inactivated by methyl- or phenylhydrazine but was only...
The dissimilatory nitrite reductase, cytochrome cd1, from Pseudomonas aeruginosa (ATCC 19429) was irreversibly inactivated by methyl- or phenylhydrazine but was only reduced by hydrazine itself. The reaction required oxygen and several turnovers, approximately four, of the cytochrome acting to transfer reducing equivalents from phenylhydrazine to oxygen. The reaction with methyl- or phenylhydrazine altered the visible spectrum of the cytochrome. Bands characteristic of reduced heme c appeared plus new features that were not characteristic of either oxidized or reduced heme d1. Extraction of the heme from phenylhydrazine-treated cytochrome yielded a covalently modified form of the original heme d1. Visible, 1H NMR, and mass spectra were obtained on the purified modified heme and on the metal-free esterified derivative. The spectroscopic data indicate that the modification was the regiospecific substitution of the 5 meso-proton by a phenyl group.
Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Cytochromes; Electron Transport Complex IV; Hydrazines; Hydroquinones; Kinetics; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Monomethylhydrazine; Nitrite Reductases; Oxygen Consumption; Phenylhydrazines; Pseudomonas; Spectrophotometry
PubMed: 2155216
DOI: No ID Found -
Experimental Neurology Aug 1978The toxic derivative of hydrazine, monomethylhydrazine, at a dosage of 10 mg/kg is a potent convulsant, producing tonic-clonic seizures in the cat. In this study the...
The toxic derivative of hydrazine, monomethylhydrazine, at a dosage of 10 mg/kg is a potent convulsant, producing tonic-clonic seizures in the cat. In this study the effects of enforced restraint on susceptibility to MMH-induced seizures was examined in naive animals and in cats prepared neurosurgically with indwelling polygraphic recording electrodes. Using a counterbalanced design, latency to seizure following the intraperitoneal administration of the drug (10 mg/kg) was measured twice in all animals, under restraint and in freely moving conditions. Susceptibility to seizures was significantly decreased under the condition of restraint. Additionally, polygraphic recordings showed that restraint was accompanied by an increased incidence of “synchronous” EEG patterns. These results were not explained by metabolic variables, duration of intertrial interval, or changes in weight. The relationship between observed polygraphic patterns and seizure response is discussed in terms of the physiological alterations attendant upon restraint.
Topics: Animals; Cats; Electroencephalography; Female; Male; Methylhydrazines; Monomethylhydrazine; Restraint, Physical; Seizures
PubMed: 680066
DOI: 10.1016/0014-4886(78)90187-5 -
British Journal of Cancer Nov 19741,2-Dimethylhydrazine, in contrast to 1-methylhydrazine, is a potent carcinogen for the colon in rats and mice. 1,2-[(14)C]Dimethylhydrazine was administered to rats and...
1,2-Dimethylhydrazine, in contrast to 1-methylhydrazine, is a potent carcinogen for the colon in rats and mice. 1,2-[(14)C]Dimethylhydrazine was administered to rats and mice in doses which are carcinogenic following a single dose in the former species, or carcinogenic on repeated administration in the latter species, and the rate of (14)CO(2) exhalation was measured. Exhalation of (14)CO(2) was also studied after administration of single doses of 1-[(14)C]methylhydrazine to mice. Incorporation of radioactivity into the nucleic acids of a variety of organs was found at a time after injection (about 6 h) when (14)CO(2) production from both compounds was virtually complete. Methylation of nucleic acids of liver and colon, as indicated by the formation of 7-methylguanine, was observed after treatment with 1,2-dimethylhydrazine and to a smaller extent by a factor of about 10 after treatment with 1-methylhydrazine. Less than 1% of a single dose of 1,2-[(14)C]dimethylhydrazine was excreted in the bile of rats as determined by chemical and radioactivity assays. The similarities of the biological and biochemical actions of 1,2-dimethylhydrazine with those of some nitroso compounds and of cycasin (methylazoxymethanol glucoside) are emphasized.
Topics: Alkylation; Animals; Bile; Carbon Dioxide; Colon; Dimethylhydrazines; Female; Guanine; Hydrazines; Liver; Male; Mice; Monomethylhydrazine; Nucleic Acids; Rats
PubMed: 4469196
DOI: 10.1038/bjc.1974.218 -
British Journal of Cancer Nov 1974Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes...
Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1-dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2-dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.
Topics: Animals; Colonic Neoplasms; Dimethylhydrazines; Endoplasmic Reticulum; Hydrazines; Kidney Neoplasms; Lethal Dose 50; Leucine; Liver; Male; Mice; Mitochondria; Monomethylhydrazine; Neoplasms; Neoplasms, Experimental; Rats; Ribosomes
PubMed: 4469195
DOI: 10.1038/bjc.1974.217 -
British Journal of Cancer Sep 1974Activities of N-acetyl-β-D-glucosaminidase, N-acetyl-β-D-galactosaminidase, β-D-galactosidase and α-L-fucosidase were measured in rat colonic tumours induced by...
Activities of N-acetyl-β-D-glucosaminidase, N-acetyl-β-D-galactosaminidase, β-D-galactosidase and α-L-fucosidase were measured in rat colonic tumours induced by 1,2-dimethylhydrazine. Tumours varied considerably in their enzyme content, not only from different animals but also from the same animals. Enzymatic heterogeneity among tumours appeared to be related to their site of origin in the colon. The descending colon, which after the DMH treatment showed a significant increase in the levels of glycosidases, also gave rise to a larger number of adenocarcinomata than other parts of the colon. The relative changes in the activities of four glycosidases seemed to show a good correlation.
Topics: Animals; Colonic Neoplasms; Galactosidases; Glucosidases; Glycoside Hydrolases; Hexosaminidases; Hydrazines; Injections, Subcutaneous; Intestinal Mucosa; Kinetics; Male; Monomethylhydrazine; Neoplasms, Experimental; Rats
PubMed: 4451627
DOI: 10.1038/bjc.1974.186 -
The Journal of Investigative Dermatology Jun 1966Finely divided methylhydrazine sulfate was fed to 42 rats at a concentration of 300 mg per kg of ground commercial diet. After 42 days most of the rats developed...
Finely divided methylhydrazine sulfate was fed to 42 rats at a concentration of 300 mg per kg of ground commercial diet. After 42 days most of the rats developed hyperkeratosis and edema of the terminal 2-6 cm of the tail. Twenty-five rats fed longer than 98 days all developed tail tip gangrene varying in length from 0.4 to 2.5 cm. Since 24 control rats which were fed the ground commercial diet grew satisfactorily and did not develop any alterations in the skin of the tail, the tail tip gangrene is ascribed to the presence of MHS in the diet. In view of the presence of epidermal hyperplasia and edema in every instance, and the occurrence of acute folliculitis in a majority of test rats, the tail tip gangrene is believed to be due to epithelial alterations rather than an injury of the blood vessels. This experimental model may prove useful for epidermal studies, because MHS fed rats are active and energetic. Secondly, the MHS skin changes apparently can be produced more rapidly than with diets deficient in unsaturated fatty acids.
Topics: Animals; Gangrene; Male; Monomethylhydrazine; Rats; Rats, Sprague-Dawley; Skin; Tail
PubMed: 25622423
DOI: 10.1038/jid.1966.83 -
Applied Microbiology Jan 1965The sporicidal activity of components used in liquid and solid rocket propellants was tested by use of spores of Bacillus subtilis dried on powdered glass. Liquid...
The sporicidal activity of components used in liquid and solid rocket propellants was tested by use of spores of Bacillus subtilis dried on powdered glass. Liquid propellant ingredients tested were N(2)O(4), monomethylhydrazine and 1,1-dimethylhydrazine. N(2)O(4) was immediately sporicidal; the hydrazines were effective within several days. Solid propellants consisted of ammonium perchlorate in combination with epoxy resin (EPON 828), tris-1-(2-methyl) aziridinyl phosphine oxide, bis-1-(2-methyl) aziridinyl phenylphosphine oxide, and three modified polybutadiene polymers. There was no indication of appreciable sporicidal activity of these components.
Topics: Bacillus subtilis; Dimethylhydrazines; Hydrazines; Oxides; Research; Space Flight; Spores; Spores, Bacterial
PubMed: 14264838
DOI: 10.1128/am.13.1.10-14.1965