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PubMed1997

Triglyceride disposition in isolated hepatocytes after treatment with hydrazine.

Treatment of animals with hydrazine causes the accumulation of triglycerides in the liver but the mechanism remains unclear. Therefore, the effect of hydrazine on hepatic triglyceride synthesis and subsequent transport was studied in a hepatocyte model, in vitro in order to isolate liver cells from extrahepatic influences. Hepatocytes were isolated and either incubated in suspension with [14C]palmitate in the presence of hydrazine (2-12 mM) or pre-incubated with [14C]palmitate, washed free of the fatty acid and then incubated with hydrazine (2-12 mM). Hydrazine resulted in a significant reduction in the incorporation of [14C]palmitate into triglycerides and reduction in the transportation of triglycerides out of cells. When [14C]palmitate was in the incubation medium, ATP levels were reduced by lower concentrations of hydrazine than have previously been reported. None of the concentrations of hydrazine used affected cell membrane integrity (viability) as measured by LDH leakage. The 14CO2 produced by the beta-oxidation of [14C]palmitate was also measured in short term incubations (30 min) carried out in sealed vessels. There was a dose dependent increase in 14CO2 produced by very low concentrations of hydrazine (0.01-0.1 mM) after which the effect was maximal and concentrations above 8 mM hydrazine decreased 14CO2 production. The data suggest that the inhibition of transportation of triglycerides out of cells by hydrazine may have a more important role in the accumulation of triglycerides in the liver than has been previously recognised. However, the model was not able to mimic the accumulation of triglycerides in hepatocytes seen in vivo.

Animals↗
PubMed1986

The role of formaldehyde in hydrazine-induced methylation of liver DNA guanine.

Administration of the hepatotoxin and carcinogen, inorganic hydrazine, to rodents results in the formation of 7-methylguanine and O6-methylguanine in liver DNA; co-administration of [methyl-14C]methionine or [14C]formate with the hydrazine labels the methylguanines, suggesting involvement of the 1-carbon pool in the methylation process. The present study investigates the proposal that the methylation mechanism involves reaction of hydrazine with endogenous formaldehyde to yield formaldehyde hydrazone, which could be metabolized to the potent methylating agent diazomethane. Hamsters were pretreated with methanol, ethanol or cyanamide to alter the endogenous hepatic aldehyde levels prior to administration of hydrazine. Formaldehyde levels were refractory to the pretreatments; hepatic acetaldehyde levels were increased, but hydrazine administration under such conditions did not result in the formation of ethylated guanines in DNA. Methanol and ethanol inhibited hydrazine-induced methylation of DNA. Hydrazine incubated with liver S9 fraction and calf thymus DNA induced the formation of 7-methylguanine and O6-methylguanine when formaldehyde was present in the incubation system; substitution of formaldehyde with acetaldehyde in the incubation medium did not result in any detectable alkylation of DNA. Both liver microsomal and cytosolic fractions demonstrated heat-labile activity in supporting the hydrazine-induced methylation process. Tetraformyltrisazine, or a similar reaction product of hydrazine and formaldehyde, may be a more important intermediate than formaldehyde hydrazone in the hydrazine-induced methylation of DNA.

Aldehydes↗
PubMed1987

Methylation of DNA guanine during the course of induction of liver cancer in hamsters by hydrazine or dimethylnitrosamine.

Hydrazine is carcinogenic to the mouse and rat, but three earlier studies have reported no carcinogenicity of hydrazine in the hamster. Administration of hydrazine to mice, rats and hamsters results in rapid methylation of liver DNA guanine for which endogenous formaldehyde appears to be the source of the methyl moiety. Hamsters were given hydrazine sulfate at 170, 340 and 510 mg/l in the drinking water for 2 years [average dose of 4.6, 8.3 and 10.3 mg hydrazine (free base)/kg body wt over the 2-year period], during which levels of methylation of DNA guanine in liver, kidney and lung, and histopathologic examinations of these tissues were carried out; dimethylnitrosamine, as a positive control, was administered at 10 mg/l in the drinking water (average dose of 1.1 mg/kg body wt over the 4-month measurement period). Both 7-methylguanine and O6-methylguanine were readily detectable at 6 months exposure in hamsters given hydrazine or dimethylnitrosamine; in hydrazine-treated animals only trace amounts of these bases could be detected after 12 months exposure; these bases were again detected in liver DNA at exposure times of 18 and 24 months. Hepatocellular carcinomas were observed in hamsters treated at the highest dose of hydrazine sulfate after 78 weeks of exposure; the incidence of liver cancer was dose-related over the course of the experiment: 32% for hamsters exposed to 510 mg hydrazine sulfate/l, 12% for 340 mg/l and none at 170 mg/l. Hamsters given dimethylnitrosamine developed high levels of 7-methylguanine and even higher levels of O6-methylguanine and both liver cholangiocellular carcinomas (73% incidence), as reported before, and hepatocellular carcinomas (27% incidence), a new finding. These results demonstrate for the first time that hydrazine is a liver carcinogen in the hamster and provide new information regarding the accumulation of DNA damage during the entire induction period for the carcinomas.

Animals↗
PubMed1980

Regulation of formation in vivo of pyridoxal phosphate in hydrazine-treated rats.

The formation in vivo of pyridoxal phosphate 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 administered at the present dose did not appear to have an effect on the pyridoxal phosphate level of either liver on kidney tissue. Hydrazine treatment, however, elevated the pyridoxal level in liver, while kidney pyridoxal level remained unaltered under the same condition. The pyridoxine phosphate oxidase activity in liver, unlike that in kidney, was found to be increased after hydrazine treatment. The increase in pyridoxine phosphate oxidase activity in the liver of hydrazine-treated rats was prevented by actinomycin D treatment. It has been suggested that hydrazine treatment at the present dose enhanced the rate of formation of pyridoxal phosphate from pyridoxine-5-phosphate in liver, while the formation of pyridoxal phosphate in kidney appeared to be independent of hydrazine treatment. The increased activity of liver pyridoxine phosphate oxidase in hydrazine-treated rats was ascribed to the induction of the enzyme. It has been further suggested that the unalteration in the liver pyridoxal phosphate level in hydrazine-treated rats inspite of enhanced conversion of pyridoxine-5-phosphate to pyridoxal phosphate, was probably caused by the increased hydrolysis of pyridoxal phosphate.

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↗
PubMed1986

Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions.

The enzyme systems in rat liver and lung responsible for the oxidative metabolism of hydrazine derivatives were studied to determine whether these enzymes, cytochrome P-450 and monoamine oxidase, were responsible for metabolically activating hydrazines to carcinogenic/toxic metabolites. Cytochrome P-450 preferentially oxidized the nitrogen to nitrogen bond of 1,2-disubstituted hydrazines and hydrazides, while monoamine oxidase oxidized the nitrogen to nitrogen bond of all the classes of hydrazine derivatives that were tested. Oxidation of the nitrogen to nitrogen bond led to the formation of stable azo intermediates in the case of 1,2-disubstituted hydrazines and to unstable monoazo (diazene) metabolites in the case of monosubstituted hydrazines and hydrazides. In addition, cytochrome P-450 preferentially oxidized the carbon to nitrogen bond of monoalkylhydrazines; this reaction resulted in the formation of aldehyde metabolites (via hydrazone intermediates). Monosubstituted hydrazines were shown to be potent, irreversible inhibitors of mitochondrial monoamine oxidase. In contrast, the 1,2-disubstituted hydrazines appeared to be good substrates for the monoamine oxidase and served as competitive inhibitors at high concentrations. There did not appear to be any monoamine oxidase isozyme (form A or B) specificity in the metabolism of either the 1,2-disubstituted hydrazines or the monoalkylhydrazines, ethyl- and n-propylhydrazine.

1,2-Dimethylhydrazine↗
PubMed1994

Hydrazine-mediated DNA damage: role of hemoprotein, electron transport, and organic free radicals.

The hydrazines represent an important class of xenobiotic agents encountered in the environment, in industrial settings, and in medical therapeutics. Agents with a hydrazine functionality are metabolized to toxic intermediates capable of damaging cellular macromolecules and stimulating proteolysis. Phenylhydrazine (PH), methylhydrazine (MH), hydrazine (HY), and the therapeutic agents phenelzine (PZ) and hydralazine (HD) were examined for their ability to undergo metabolism via HbO2 and to cause damage to added supercoiled phi x174 RF DNA. The hydrazines, when incubated in hemolysate, caused a time- and concentration-dependent strand scission of DNA as monitored using phi x174 RF DNA. The rank order for hydrazine-mediated damage was phenylhydrazine > phenelzine > hydrazine > hydralazine > methylhydrazine. In addition, hydrazine-mediated damage to DNA increased in proportion to protein concentration (i.e., HbO2 content) of the hemolysate. To examine whether the DNA damage resulted primarily from organic free radicals or reactive oxygen free radical species, a series of mechanistic studies employing antioxidants and a free radical scavenger was initiated. The antioxidants dimethylfuran, dimethyl sulfoxide, and dimethylthiourea failed to inhibit hydrazine-mediated DNA damage in hemolysate. In contrast, the free radical spin trap agent dimethylpyrrolidin-N-oxide effectively inhibited PH-mediated DNA damage, while the free radical scavenger N-acetylcysteine also showed a protective effect against PH-, PZ-, HD-, HY-, and MH-mediated DNA strand scission. Potassium ferricyanide-mediated methemoglobin formation and imidazole, a ligand for the heme moiety of hemoglobin, both inhibited PH-stimulated DNA damage in hemolysate demonstrating the importance of oxyhemoglobin to the process. These results suggest that organic free radicals play a dominant role, relative to oxygen free radical species, in hydrazine-mediated DNA strand scission.

DNA Damage↗
PubMed1994

Hydrazine genotoxicity in the neonatal rat.

The neonatal rat, because of its relatively rapid rate of liver DNA replication without chemical or surgical induction, was used to assess the genotoxicity of the carcinogen hydrazine. Hydrazine is a more potent acute toxicant in the neonate than in the adult rat. Administration of hydrazine sc (1.5-50 mg/kg body wt) to newborn rats during the period of rapid liver DNA synthesis, 72-96 hr after birth, resulted in the formation of 7-methylguanine and O6-methylguanine in hepatic DNA; O6-methylguanine was seen only in animals given near-lethal doses of the carcinogen. Methylguanines were detectable in liver DNA only when the dose of hydrazine was necrogenic, but lethal doses of hydrazine to neonates produced more methylguanines in liver DNA than in adult rats given equal doses. Southern analyses were performed on liver DNA from neonates treated with 25 or 50 mg hydrazine/kg, doses which were necrogenic to the liver. The results indicated that one or more MspI restriction sites (5'-C decreases CGG-3') were lost or blocked in liver DNA from hydrazine-treated animals and that these sites were located at or near the genes for gamma-glutamyl transpeptidase and cytochrome P450 IIB1. Restriction sites near albumin, H-ras, and cytochrome P450 IIE1 genes cut by MspI, HpaII, or HhaI did not appear to be affected by hydrazine treatment. The results suggest that hydrazine-induced damage is not random in the DNA molecule. The neonate shows less DNA adduct formation at low doses of hydrazine, but higher levels at high doses.

Animals↗
PubMed1983

Methylation of liver DNA guanine in hamsters given hydrazine.

Formation of 7-methylguanine and O6-methylguanine in liver DNA was measured 24 hr after administration of various single oral doses of 15 to 120 mg hydrazine/kg body wt to Syrian golden hamsters, and at various times up to 96 hr after a single oral dose of 90 mg hydrazine/kg body wt. Formation of these bases in hamster liver DNA appeared similar to that reported earlier for rats and mice treated with necrogenic doses of hydrazine; however, persistence of O6-methylguanine in liver DNA following hydrazine administration was longer in hamster than in rat liver DNA. Administration of hydrazine sulfate in the drinking water of hamsters over a 9-week period resulted in accumulation of both 7-methylguanine and O6-methylguanine in liver DNA to the extent that about 2 out of every 10,000 guanine bases were methylated at each position on the base. Diethyl maleate pretreatment of hamsters depleted liver stores of glutathione and blocked DNA methylation in hydrazine-treated animals; however, buthionine sulfoximine, which also depleted glutathione stores, had no effect on the DNA methylation response to hydrazine poisoning in Sprague-Dawley rats. Hydrazine administration to hamsters and Swiss Webster mice resulted in more 7-methylguanine and O6-methylguanine in liver DNA than did administration of monomethylhydrazine, a proposed intermediate in the hydrazine-DNA methylation response. Even at the highest feasible dose of monomethylhydrazine to hamsters, no methylguanines could be detected, while these aberrant bases were readily quantifiable following hydrazine administration; thus, no evidence was obtained to support the proposal that monomethylhydrazine is an important intermediate in the methylation of DNA guanine in hydrazine-treated animals.

Animals↗
PubMed1999

Effect of hydrazine upon vitamin B12-dependent methionine synthase activity and the sulphur amino acid pathway in isolated rat hepatocytes.

The effect of the industrial chemical, hydrazine (4-12 mM), on methionine synthase (EC 2.1.1.13) activity and levels of the sulphur amino acids homocysteine, cysteine, and taurine as well as GSH were investigated in vitro in isolated rat hepatocyte suspensions and monolayers in order to explain some of the adverse in vivo effects of hydrazine. None of the concentrations of hydrazine were overtly cytotoxic in hepatocyte suspensions (measured as lactate dehydrogenase [LDH] leakage) after 3 hr. However, after 24 hr in culture cells treated with 12 mM, hydrazine showed a significant increase in LDH leakage. Methionine synthase activity was reduced by hydrazine (8 and 12 mM) in suspensions (by 45 and 55%, after 3 hr) and monolayers (12 mM; 65-80% after 24 hr). This was not due to nitric oxide production and the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine, failed to protect against the hydrazine-induced loss of ATP and GSH and the reduction in urea synthesis at 24 hr. Homocysteine export was increased by 6 mM hydrazine, and total taurine content of treated cells was increased by 12 mM hydrazine. Thus, hydrazine was found to have several important and possibly deleterious effects on some parts of the sulphur amino acid pathway.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

Effect of fructose on the biochemical toxicity of hydrazine in isolated rat hepatocytes.

Rat hepatocyte suspensions were incubated with various concentrations of hydrazine (0, 8, 12, 16, 20 mM) for 1, 2 and 3 h. In some experiments fructose (10 mM) was added either during the preincubation period, or 1 h after the start of hydrazine treatment. In certain experiments in which fructose was added, the glycolytic inhibitor sodium fluoride (3 mM) was also added during the preincubation period. Hepatocytes incubated with hydrazine alone demonstrated both a concentration- and time-dependent loss of cell viability as measured by increased Trypan blue uptake and lactate dehydrogenase (LDH) leakage. These parameters were reduced and delayed by fructose when added either before or 1 h after hydrazine treatment. There was also both a concentration- and time-dependent loss of ATP and reduced glutathione (GSH) content with hydrazine treatment. Moreover, fructose caused an initial rapid depletion of ATP but thereafter ATP levels were increased in control hepatocytes. Fructose reduced both the depletion of ATP and GSH in hydrazine- treated hepatocytes. Urea synthesis was inhibited by all concentrations of hydrazine studied but fructose treatment after 1 h did not alter this. This study also demonstrated that fluoride, an enolase inhibitor, abolished the protection against depletion of ATP levels provided by fructose, without affecting cell viability or GSH levels. These findings suggest that the cytotoxicity of hydrazine and its effects on urea synthesis and GSH levels are not a direct result of ATP depletion. The protective effects of fructose against the cytotoxicity may be due to a direct interaction with hydrazine.

Adenosine Triphosphate↗
PubMed1994

Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B.

PURPOSE: To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study. PATIENTS AND METHODS: Between July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of hydrazine sulfate on nutritional status, performance status, and quality of life was also assessed. RESULTS: Analysis of 266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfate-treated group compared with 7.70 months for the placebo-treated group (P = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurred in 65% of hydrazine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred significantly more often in patients treated with hydrazine sulfate. Quality of life was significantly worse in patients who received hydrazine sulfate. CONCLUSION: This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Role of cytochrome P450 in hydrazine toxicity in isolated hepatocytes in vitro.

1. Hepatocytes, isolated from the control, diethyldithiocarbamate (DEDC), acetone, isoniazed and hydrazine pretreated rat, were incubated with hydrazine (8-20 mM) for 3 h. Hydrazine caused a dose-dependent loss of viability, leakage of LDH, depletion of GSH and ATP and an inhibition of the incorporation of 3H-leucine into protein. 2. Pretreatment with DEDC increased, whereas hydrazine and acetone pretreatments decreased the cytoxicity and biochemical effects of hydrazine. Pretreatment with isoniazid slightly increased hydrazine cytotoxicity. Acetone pretreatment reduced the inhibition of protein synthesis caused by hydrazine compared to the control. 3. 4-Nitrophenol hydroxylase activity (P4502E1) correlated with viability, LDH leakage, ATP and GSH depletion in cells from the control, DEDC, acetone and hydrazine pretreated rats. 4. The activities of PROD (P4502B1) and EROD (P4501A1/1A2) also correlated with the above parameters for all treatments. The results suggest that three isoenzymes may be involved in the detoxication of hydrazine. Protein synthesis inhibition did not correlate with the activities of any of the enzymes measured.

Acetone↗
PubMed1982

Studies on the possible mechanism of hydrazine action on ascorbic acid-metabolising enzymes.

The activities of enzymes associated with the synthesis and degradation of L-ascorbic acid were studied in hydrazine-treated rats supplemented with pyridoxine. The effects of hydrazine in vitro were also examined on these enzymes. The activity of liver D-glucuronoreductase was reduced in hydrazine-treated rats even after receiving pyridoxine in excess. But, the decreased activities of liver and kidney dehydroascorbatases in hydrazine-treated rats were reversed by pyridoxine supplementation. Hydrazine in vitro could not inhibit the activity of liver D-glucuronoreductase or L-gulonooxidase. The drug was also unable to inhibit in vitro the activity of liver and kidney dehydroascorbatases. Studies with dialyzed liver homogenates showed that the diminished activity of D-glucuronoreductase in the liver of hydrazine-treated rats was maintained even after dialyzing the tissue preparations. In contrast, the reduced activity of dehydroascorbatase in the liver of hydrazine-treated rats was abolished following dialysis of the liver preparations. It has been suggested that the diminished activity of liver D-glucuronoreductase after hydrazine treatment might arise from the reduced synthesis of enzyme protein, while the reduction in the activity of dehydroascorbatase following hydrazine treatment could be ascribed to depletion in vivo of pyridoxal phosphate and/or to the involvement of some dialyzable factors.

Animals↗
PubMed1998

Role of Water in the Intercalation of Kaolinite with Hydrazine.

A low-defect kaolinite of 7.18-Å basal spacing was expanded upon intercalation with hydrazine. The 001 d-spacing was broad and the peak resolved into components at 10.28, 9.48, and 8.80 Å. It was found that the ordered kaolinite predominantly expanded to 9.48 Å with 31.2% and 10.28 Å with 38.0% of the total peak area. A high-defect kaolinite showed expansion by hydrazine in identical steps with d-spacings of 10.27, 9.53, and 8.75 Å. It is proposed that the intercalation of the kaolinite by hydrazine occurs according to the orientation of the hydrazine molecule and that water plays an integral part in the process of kaolinite expansion. For the hydrazine-intercalated kaolinite, hydroxyl stretching bands attributed to water are observed at 3413, 3469, and 3599 cm-1 for the low-defect kaolinite and at 3600 and 3555 cm-1 for the high-defect kaolinite. Upon the exposure of the low-defect hydrazine-intercalated kaolinite to air, an additional water band is observed at 3555 cm-1. Water bending modes are observed at 1578, 1598, 1612, 1627, 1650, and 1679 cm-1 for the hydrazine-intercalated low-defect kaolinite and at 1578, 1598, 1613, 1627, 1652, and 1678 cm-1 for the hydrazine-intercalated high-defect kaolinite. The intensities of these bands are a function of the exposure to air and measurement time. The 1650- and 1679 cm-1 bands increased in intensity as the intensity of the 1612 cm-1 band decreased. Even after exposure to air for 24 h, water remained in the kaolinite interlayer space and only after heating was the water removed. The 1578, 1598, and 1612 cm-1 bands as well as the 1627 cm-1 band are attributed to (a) free or non-hydrogen-bonded water held in the interlayer spaces of the kaolinite, (b) water in the hydration spheres of the hydrazine, and (c) adsorbed water on the kaolinite surface. In kaolinites additional bands at 1650 and 1679 cm-1 are attributed to water coordinated to the siloxane surface. Copyright 1998 Academic Press.

Journal Article↗
PubMed2002

Evaluation of hydrazine reduction by cellulose acetate filters using infrared tunable diode laser spectroscopy.

Cellulose acetate (CA) filters have been investigated to determine their hydrazine (N2H4) breakthrough characteristics using a system based on tunable diode laser absorption spectroscopy (TDIAS). The breakthrough mass loading sorption curves for hydrazine were dependent on both the flow rate and the concentration. In experiments using a 4.5 ppmv hydrazine standard, the amounts of hydrazine retained by the CA filter were 4.25 microg at a flow rate of 2.82 L/min and 65 microg at a flow rate of 0.28 L/min. These loadings are much greater than the 31.5 ng/cigarette of hydrazine reported in smoke for unfiltered cigarettes. Further, CA filters exposed to four and eight puffs of smoke actually made the filter more efficient in retaining hydrazine compared to CA filters that had not been exposed to smoke. Therefore, if hydrazine is present in smoke at the levels reported in unfiltered cigarettes, all of the hydrazine would be trapped by the CA filter, and would be unable to break through during smoking. A unique feature of this analytical method is that the instrument does not require calibration after molecular parameters have been determined, in this case from previously acquired quantitative hydrazine FT-IR reference spectra.

Journal Article↗
PubMed1990

Course of ATP depletion in hydrazine hepatotoxicity.

The effect of hydrazine on ATP levels has been investigated in rats in vivo and in hepatocytes in vitro. Hydrazine was found to cause a dose-dependent depletion of hepatic ATP in vivo 3 h after dosing. In isolated hepatocytes in vitro hydrazine also caused a concentration-dependent depletion of ATP which preceded cytotoxicity as indicated by loss of cell viability. The ATP depletion in isolated hepatocytes was also significant at a concentration of hydrazine which was not cytotoxic. Attempts to determine hepatic ATP depletion in vivo over time using topical 31P NMR were confounded by the effects of the thiopentobarbitone used to anaesthetise the animals. This was found to ameliorate the effects of hydrazine on ATP depletion but potentiate the lethality of hydrazine. Consequently, although ATP depletion was detected in some hydrazine-treated animals, this was only observed in animals which subsequently died. The results indicate that ATP depletion may underlie the hepatotoxicity of hydrazine.

Adenosine Triphosphate↗
PubMed1984

The haemolytic reactions of 1-acetyl-2-phenylhydrazine and hydrazine: a spin trapping study.

Free radical production from the reaction of hydrazine and 1-acetyl-2-phenylhydrazine (AcPhHZ) with oxyhaemoglobin and with human red blood cells, has been observed by the electron spin resonance technique of spin trapping. Using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), the free radical intermediates detected depended on the hydrazine derivative, oxyhaemoglobin and the oxyhaem/hydrazine derivative concentration ratio. The reaction of hydrazine with oxyhaemoglobin in the presence of DMPO gave a nitroxide which was identified as a reduced dimer of DMPO. Whereas hydrazine-treated red blood cells, in the presence of DMPO, gave a nitroxide spin adduct which was identified as the hydroxyl radical spin adduct of DMPO, 5,5-dimethyl-1-pyrrolidino-1-oxyl (DMPO-OH). The reaction of AcPhHZ with oxyhaemoglobin, in the presence of DMPO, gave DMPO-OH, the phenyl radical spin adduct of DMPO, 5,5-dimethyl-2-phenylpyrrolidino-1-oxyl (DMPO-Ph) and an oxidised derivative of DMPO, 5,5-dimethyl-2-pyrrolidone-1-oxyl (DMPOX). The amounts of DMPO-Ph, DMPO-OH and DMPOX observed depended on the 1-acetyl-2-phenyl-hydrazine/oxyhaemoglobin concentration ratio; DMPOX replaced DMPO-OH as the concentration of AcPhHZ was decreased. DMPOX production has been previously associated with the production of highly oxidised haem iron-oxygen intermediates. AcPhHZ treated red blood cells gave DMPO-Ph and DMPO-OH spin adducts in the presence of DMPO. DMPO had little to no effect on the rate of oxygen consumption by oxyhaemoglobin with hydrazine and AcPhHZ. Moreover, the rate of oxyhaemoglobin oxidation induced by hydrazine, was not decreased by DMPO whereas the rate of oxyhaemoglobin oxidation induced by AcPhHZ was decreased approx. 40% by DMPO. DMPO (10 mM) gave a small decrease in haemolysis and lipid peroxidation induced by 1 mM hydrazine and AcPhHZ in a 1% suspension of red blood cells.

Carboxyhemoglobin↗