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At least 19 recordsLinked to original sources
PubMed1978

Effect of hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine on guanylate cyclase activity.

The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored.

Animals↗
PubMed1975

[Newer antimycotics. I. Derivatives of phenyl-hydrazine (author's transl)].

The author produced a number of derivatives of phenyl-hydrazine and its analogues, investigated their antimicrobial efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of phenyl-hydrazine-derivatives. From the author's results it can be concluded that the halogen-substituted phenyl-hydrazines and their N-(acetyl)-derivatives exert a moderate fungistatic effect (Tab. 1). In the series of N-aryl-sulphonyl-N'-phenyl-hydrazines only the compounds derived from 3,4-dichloro-phenyl-hydrazine proved to be effective; the other representatives of this type were fully ineffective (Tab. 1). The majority of the halogen-substituted N-aroyl-N'-phenyl-hydrazines exerted a relatively strong fungistatic activity with a broad spectrum of efficiency (Tab. 2). On the contrary, their analogues having a -CO-NH- group in place of the -CO-NH-NH-group, were fully inactive (Tab. 3). From the investigated derivatives of phenyl-hydrazine, the N-benzoyl-, N-(2-chloro-benzoyl)-, N-(4-chloro-benzoyl)- and N-furoyl-derivatives of 3- and 4-chloro-phenyl-hydrazine, furthermore the N-benzoyl- and N-furoyl-derivatives of 3,4-dichloro-phenyl-hydrazine were most effective (Tab. 2). The acute toxicity in the mouse of these effective compounds was relatively small; they were found to be significantly less toxic than tetramethyl-thiuramdisulfide (Tab. 4). On the basis of an intensive fungistatic efficiency and small toxicity of the halogen-substituted N-aroyl-N'-phenyl-hydrazines, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses, and also in the chemoprophylaxis of certain phytomycoses.

Alternaria↗
PubMed1992

Studies on the disposition and metabolism of hydrazine in rats in vivo.

1. Rats were given various doses of hydrazine orally and their plasma and liver hydrazine levels were determined (at various times up to 270 min after dosing) by gas chromatography/mass spectrometry. 2. The increase in the peak plasma level and in the area under the plasma concentration-time curve (AUC) were not directly proportional to the dose. 3. The ratio of plasma to liver hydrazine varied with dose suggesting saturation of an uptake mechanism might be occurring. 4. In a separate experiment hydrazine was still detectable in the plasma and liver 24 h after dosing with hydrazine i.p. 5. Rats were given the same doses of hydrazine and urine was collected for 24 h after dosing and assayed for hydrazine and acetylhydrazine. The proportion of hydrazine and acetylhydrazine excreted declined with dose. 6. Liver samples were taken for histopathological examination 96 h after dosing. Only after the highest dose (81 mg kg-1) was there evidence of fatty liver, 96 h after a single dose, and a reduction in both liver and body weight.

Animals↗
PubMed1978

Some studies on ascorbic acid metabolism in hydrazine-treated rats.

The metabolism of ascorbic acid was studied in hydrazine-treated rats. Hydrazine was administered i.p. at a dose of 1.28 mg/day (20% LD50) for each 100 g body weight for 7 days. Hydrazine administration at the present dose did not appear to have an effect on the total ascorbic acid level of liver, kidney, spleen and testis. The adrenal and plasma total ascorbic acid levels were, however, elevated. The activity of liver D-glucuronoreductase and that of liver and kidney dehydroascorbatases were diminished after hydrazine administration. The changes in the activities of liver enzymes were accompanied by a fall in the reduced ascorbic acid level and an elevation in the dehydroascorbic acid level. The uronolactonase activity of liver, on the other hand, remained independent of hydrazine treatment. It has been suggested that hydrazine treatment at the present dose reduced the biosynthesis of L-ascorbic acid from D-glucuronolactone as substrate. In spite of diminished synthesis, the normal level of total ascorbic acid in the liver of hydrazine-treated rats was maintained by reducing the degradation of L-ascorbic acid. The rise in the plasma total ascorbic acid level after hydrazine treatment was ascribed to reduced catabolism and urinary excretion of ascorbic acid, while the elevation in adrenal total ascorbic acid level might result from increased uptake of ascorbic acid by the gland from blood or from nonfunctional accumulation.

Alcohol Oxidoreductases↗
PubMed1979

Effect of hydrazine exposure on hepatic triacylglycerol biosynthesis.

Acute hydrazine exposure elevated rat liver triacylglycerol content and produced a rapid rise in triacylglycerol production from sn-[1,3-14C]glycerol 3-phosphate by liver homogenate and microsomal fractions. Hydrazine treatment also increased the incorporation of [1,3-14C]glycerol into hepatic triacylglycerol by the intact animal. Homogenates of hepatocyte monolayers exposed to hydrazine in vitro also exhibited an increased capacity to form triacylglycerol from sn-[1,3-14C]glycerol 3-phosphate. Hydrazine-dependent increases in hepatic triacylglycerol production measured in vitro correlated well with an increase in microsomal phosphatidate phosphohydrolase (EC 3.1.3.4) activity. Therefore, the fatty liver associated with hydrazine exposure may be explained in part by a rise in the enzymatic capacity of hepatic triacylglycerol biosynthesis.

Animals↗
PubMed1979

Hydrazines as mutagens in a histidine-requiring auxotroph of Salmonella typhimurium.

Hydrazines have been found naturally in tobacco and mushrooms. Other hydrazines are used in industry, medicine, and agriculture. Although about 38 hydrazines are carcinogenic, few, if any, have been tested successfully in rapid bacterial mutagenesis assays. We have utilized a tester strain of Salmonella typhimurium (TA1530) in order to determine the mutagenic activity of a number of hydrazines and related compounds. This strain is thus shown to be effective as a tester organism for the facile detection of hydrazines as mutagens.

Dose-Response Relationship, Drug↗
PubMed1977

[Mechanism of increasing the effect of antineoplastic agents by hydrazine sulfate].

The results of the in vivo and in vitro experiments indicated that hydrazine sulphate is a new potent inhibitor of the biotransformation of physiologically active compounds, including those with an antitumor effect. It is suggested that hydrazine sulphate renders an inhibitory effect by retarding the access of xenobiotics to microsomal enzymes active centers metabolizing them. The retardation of antitumor compounds biotransformation effected by hydrazine sulphate in vitro enabled the explanation of the enhanced effect of cytostatics, used in combination with hydrazine sulphate in vivo. This fact seems to speak in favour of the perspective clinical application of hydrazine sulphate for potentiation of the antitumor effect of cytostatics.

Animals↗
PubMedDate not supplied

A requirement of Pi for the transitory uncoupling of rat liver mitochondria by hydrazine, when beta-hydroxybutyrate is the substrate.

We have recognized an experimental confluence between oxidative phosphorylation and chemical carcinogenesis and, therefore, became interested in the mitochondrial target of hydrazine, which is not only a potential environmental hazard as a carcinogen but is also a likely metabolite of many drugs. Hydrazine induced a Pi dependent transitory uncoupling of rat liver mitochondria when beta-hydroxybutyrate was the substrate. Uncoupling was inhibited by rutamycin; accordingly, the mitochondrial target for nucleophilic hydrazine is an electrophilic site, presumably involving activated Pi. The protective action of ATP2, ADP, PPi and Mg++ was attributed to a conformational change of the phosphorylating enzyme which participated in oxidative phosphorylation. In a mitochondrial system which included ATP gramicidin potassium ion and sulfate, hydrazine, acting as a large cation but not as a nucleophile, blocked mitochondrial swelling and the increment in ATPase activity associated with potassium ion. These data in conjunction with our previous reports dealing with other carcinogens and certain of their derivatives also contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis and are compatible with toxic effects of hydrazine on mitochondria observed previously by others.

Adenosine Diphosphate↗
PubMed1979

Identification and quantitation of hydrazine in the urine of patients treated with hydralazine.

Hydrazine has been identified by gas chromatography-mass spectrometry in the 0- to 24-hr urine of patients administered hydralazine. With a specific gas chromatographic assay procedure, the amount of hydrazine in the 0- to 24-hr urine was determined in patients treated with various doses of hydralazine. The amount of hydrazine detected in the urine was greater in the slow acetylator phenotype than in the rapid acetylator phenotype. Studies indicated that hydrazine was not produced by chemical breakdown of hydralazine or its known metabolites in urine and therefore was unlikely to be a urinary artefact formed by chemical decomposition in the urine.

Acetylation↗
PubMed1979

Kinetics and mechanism of reaction of m-nitrobenzhydrazide and other hydrazines with acetic acid.

A comprehensive kinetic study was conducted of the reactions of m-nitrobenzhydrazide and some other hydrazines with acetic acid. The overall reaction rate for all of the compounds studied followed pseudo-first-order kinetics. The temperature dependence of the m-nitrobenzhydrazide degradation reaction was determined. The reaction rate dependence on the acetic acid concentration was found to be close to first order. High-pressure liquid chromatography was used extensively in identifying and measuring the appearance or disappearance rates of m-nitrobenzhydrazide degradation products in acetous solution. With m-nitrobenzhydrazide, the major degradation products were N,N'-bis(m-nitrobenzoyl)hydrazine, N-acetyl-N'-m-nitrobenzoylhydrazine, diacetylhydrazine, and hydrazine. The concentration profiles of these products in solution suggested a complex mechanism by which hydrazides react with acetic acid. All eight rate constants at 61 degrees in the suggested mechanism were calculated by an approximation method based on experimental data. The findings in the present study indicate that acetic acid is to be avoided as a solvent for hydrazine derivatives.

Acetates↗
PubMed1992

Proton NMR spectroscopic studies on the metabolism and biochemical effects of hydrazine in vivo.

The metabolism and disposition of hydrazine and its effects on endogenous metabolites has been studied in rats by the use of high resolution proton NMR spectroscopy of urine. Several metabolites of hydrazine were detected, notably acetyl- and diacetylhydrazine and a cyclised metabolite which results from a hydrazone formed from 2-oxoglutarate and hydrazine. Effects of hydrazine on endogenous metabolites in urine and plasma were also observed; notably a dose-related increase in urinary taurine, a dose-related increase in urinary and plasma lactate, increases in urinary alpha-alanine, beta-alanine, methylamine and a decrease in urinary 2-oxoglutarate. This study has indicated the utility of using high resolution proton NMR spectroscopy to analyse urine for both metabolites and endogenous compounds after exposure of animals to toxic substances.

Animals↗
PubMed1976

Fixation and loss of hydrazine-induced premutational damage in Haemophilus influenzae.

Premutational damage induced in Haemophilus influenzae by hydrazine appears to be fixed as final mutation only at replication as judged by the transformation assay. Fixation at replication is independent of the rec1 gene, unlike the case with nitrosocarbaryl. Prior to replication premutational damage induced by hydrazine disappears by an unknown process that is not dependent on the presence of a pyrimidine dimer excision system nor on the rec1 gene. Hydrazine does not produce detectable single-strand breaks or alkali-labile sites in the treated DNA nor gaps in DNA newly synthesized after treatment. In these respects it also differs from nitroso compounds. It is concluded that hydrazine acts to produce and altered base, possibly N(4)-aminocytosine, that produces mutations by mispairing at replication rather than by error-prone repair.

Chromosomes, Bacterial↗
PubMed1979

Enhancement by transition metals of unscheduled DNA synthesis induced by isoniazid and related hydrazines in cultured normal and xeroderma pigmentosum human cells.

In combination with transition metals (Mn(II), Cu(II), and Fe(III)), isoniazid and related hydrazine compounds induced unscheduled DNA synthesis (DNA repair) in cultured human fibroblasts. Manganese at 10(-5) and 10(-4) M strongly enhanced DNA repair induced by isoniazid, iproniazid, nialamide and hydrazine. Peak levels of DNA repair occurred at 5 x 10(-4)--10(-3) M of the 4 hydrazine compounds. Copper caused less enhancement of DNA repair while iron had no detectable effect. Without added metal, unscheduled DNA synthesis was not observed in cells treated with any of the 4 freshly-prepared hydrazine compounds. However, following preincubation in medium for 6--12 h, isoniazid alone at high concentrations (10(-2) M--10(-1) M) induced DNA repair. With isoniazid/manganese mixtures, preincubation did not further enhance DNA repair except at low concentrations of isoniazid (2--5 x 10(-4) M). Catalase reduced the DNA damage caused by preincubated isoniazid and by the isoniazid/metal mixtures. Exposure of repair-deficient xeroderma pigmentosum cells to isoniazid plus manganese resulted in a DNA-repair profile similar to that of normal cells. The results are consistent with hydrogen peroxide being a critical intermediate for the production of free radicals which cause the observed DNA damage.

Cells, Cultured↗
PubMed1992

Mutagenic activity of nine N,N-disubstituted hydrazines in the Salmonella/mammalian microsome assay.

The mutagenic activity of N,N-dimethyl-, N,N-diethyl-, N,N-dibutyl-, N,N-diisobutyl-, N,N-di(p-tolyl)-, N-ethyl-N-phenyl-, N,N-dibenzyl-, N,N-diphenyl- and N,N-diisopropylhydrazine was examined in the Salmonella/mammalian microsome assay using the strains TA1535, TA1537, TA97, TA98, TA100, TA102 and TA1530. All nine hydrazines were mutagenic in at least one tester strain, although of borderline significance for some of the compounds. The mutagenic potencies of the hydrazines varied 2-3 orders of magnitude, from very weak to moderate mutagenic activity. In general, the addition of S9 resulted in a lowering of the mutagenic activity and a lowering of the toxic properties of the hydrazines. The test results were relatively difficult to evaluate due to toxic effects of many of the test compounds on the test bacteria which may have resulted in an underestimation of the mutagenic potencies of some of the compounds. The pattern of mutagenic activity of the hydrazines in the different tester strains indicates that more than one mechanism of action may be involved in the mutagenicity.

Animals↗
PubMed1992

Manganese-mediated oxidative damage of cellular and isolated DNA by isoniazid and related hydrazines: non-Fenton-type hydroxyl radical formation.

The mechanism by which hydrazines induce damage to cellular and isolated DNA in the presence of metal ions has been investigated by pulsed-field gel electrophoresis (PFGE), DNA sequencing methods, and the ESR spin-trapping technique. For the detection of single-strand breaks by PFGE, an experimental procedure with alkali treatment has been designed. Isoniazid, hydrazine, and phenylhydrazine induced DNA single- and double-strand breaks in cells pretreated with Mn(II), whereas iproniazid did not. With isolated 32P-DNA, isoniazid produced DNA damage in the presence of Cu(II), Mn(II), or Mn(III). Iproniazid damage isolated DNA only in the presence of Cu(II). The Cu(II)-mediated DNA damage by isoniazid or iproniazid is due to active oxygen species other than hydroxyl free radical (.OH), presumably the Cu(I)-peroxide complex. Cleavage of isolated DNA by isoniazid plus Mn(II) occurred without marked site specificity. The DNA damage was inhibited by .OH scavengers and superoxide dismutase (SOD) but not by catalase, suggesting the involvement of .OH formed via O2- but not via H2O2. Consistently, in ESR experiments .OH formation was observed during Mn(II)-catalyzed autoxidation of isoniazid, and the .OH formation was inhibited by SOD, but not by catalase. Iproniazid plus Mn(II) produced no or little .OH. We propose a reaction mechanism for the .OH formation without a H2O2 intermediate during manganese-catalyzed autoxidation of hydrazine. The present and previous data raise the possibility that hydrazines plus Mn(II)-induced cellular DNA damage may occur, at least in part, through the non-Fenton-type reaction.

Autoradiography↗