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At least 19 recordsLinked to original sources

Further studies on the ex-vivo effects of procarbazine and monomethylhydrazine on rat semicarbazide-sensitive amine oxidase and monoamine oxidase activities.

Following administration of the anticancer agent, procarbazine, or one of its metabolites, monomethylhydrazine, to rats, activities of monoamine oxidases A and B (MAO A and MAO B) and of semicarbazide-sensitive amine oxidase (SSAO) were measured ex-vivo. Both compounds were found to be potent inhibitors of SSAO in tissue homogenates, exhibiting ID50 values in most tissues of approximately 8 mg kg-1 (procarbazine) and 0.08 mg kg-1 (monomethylhydrazine). Concurrent dose-dependent inhibition of MAO activities did not occur. However, in liver, potentiation of MAO B activity, to 140% of that in controls, was apparent following monomethyl-hydrazine and this effect was independent of the drug dose. Both compounds produced a dose-dependent potentiation of MAO A in brown adipose tissue, the elevation being more pronounced following monomethylhydrazine, with activity rising to 350% of that in control homogenates. In a parallel in-vitro study, monomethylhydrazine was without effect on MAO A in brown adipose tissue homogenates. By perfusing the SSAO substrate, benzylamine, through the isolated mesenteric arterial bed of the rat, it was found that pretreatment of animals with procarbazine or monomethylhydrazine reduced metabolism of this amine by a similar degree as had been determined ex-vivo in blood vessel homogenates. The results presented suggest that these compounds would be suitable for use as selective inhibitors in pharmacological examinations of SSAO function in isolated tissues and organs.

Amine Oxidase (Copper-Containing)↗

Modulation of monomethylhydrazine-induced seizures by ivermectin.

Exposure to monomethylhydrazine (MMH), a common rocket propellant, can cause dose-related central nervous system (CNS) disturbances ranging from tremors to tonic-clonic convulsions to death. MMH inhibits gamma-aminobutyric acid (GABA) synthesis in the CNS. Diazepam (BZ) acts at the GABA receptor site, and it is also here that ivermectin (AVM) is pharmacologically active. Mice were injected with 30 mg/kg MMH. Groups of 12 mice each were then given varying doses of AVM (5, 10 and 15 mg/kg), or AVM + BZ combinations (5 mg/kg AVM with 5 mg/kg BZ, 10 mg/kg AVM with 5 mg/kg BZ). Time to first convulsion and time to death were recorded over the next 7 h and all groups were monitored over the next 7 days. Times to convulsion were not altered with AVM alone, but death was significantly prevented with AVM dosages. A treatment of 10 mg/kg AVM with 5 mg/kg BZ resulted in no seizures or deaths.

Animals↗

Ion mobility spectrometry of hydrazine, monomethylhydrazine, and ammonia in air with 5-nonanone reagent gas.

Hydrazine (HZ) and monomethylhydrazine (MMH) in air were monitored continuously using a hand-held ion mobility spectrometer equipped with membrane inlet, 63Ni ion source, acetone reagent gas, and ambient temperature drift tube. Response characteristics included detection limit, 6 ppb; linear range, 10-600 ppb; saturated response, >2 ppm; and stable response after 15-30 min. Ammonia interfered in hydrazines detection through a product ion with the same drift time as that for MMH and HZ. Acetone reagent gas was replaced with 5-nonanone to alter drift times of product ions and separate ammonia from MMH and HZ. Patterns in mobility spectra, ion identifications from mass spectra, and fragmentation cross-sections from collisional-induced dissociations suggest that drift times are governed by ion-cluster equilibria in the drift region of the mobility spectrometer. Practical aspects including calibration, stability, and reproducibility are reported from the use of a hand-held mobility spectrometer on the space shuttle Atlantis during mission STS-37.

Ammonia↗

Determination of monomethylhydrazine with a high-throughput, all-fiber near-infrared spectrometer based on an integrated acoustooptic tunable filter and an erbium-doped fiber amplifier.

A novel integrated acoustooptic tunable filter (IAOTF) has been developed. This tunable filter is based on the Bragg interactions between waveguide and surface acoustic waves. Compared to (bulk) AOTF, its advantage include all-fiber construction, smaller size, narrower spectral resolution (1.7 nm), higher diffraction efficiency (37%), and lower rf power requirement (150 mW). A relatively narrow spectral tuning range (about 80 nm) is the only drawback for this integrated tunable filter. However, this disadvantage was overcome by judiciously using the filter for measurements in which its tuning range is coincident with the light source and also with absorption bands of analytes. In fact, an all-fiber, compact, high-throughput near-infrared spectrophotometer has been successfully constructed by synergistic use of this integrated AOTF and the erbium-doped fiber amplifier (EDFA), which has been shown to provide high intensity and wide spectral band-width in the near-infrared region from 1500 to 1600 nm. This spectral region is particularly useful for the determination of samples which have O-H and/or N-H groups. The all-fiber nature, compactness, high throughput, and high sensitivity of this spectrophotometer make it particularly suitable for on-line and real-time detection of trace gases in hostile environments, including leak detection of monomethylhydrazine (at a limit of detection of 191 ppm), which is often used as the hypergolic propellant for the space shuttle thruster systems.

Acoustics↗

Toxicological studies of the false morel (Gyromitra esculenta): embryotoxicity of monomethylhydrazine in the rat.

The embryotoxic and teratogenic potential of monomethylhydrazine (MMH), a toxic component of the widely consumed false morel (Gyromitra esculenta), was studied in rat. Groups of pregnant Sprague-Dawley rats received MMH as a constant i.v. infusion via implanted osmotic minipumps (1.2, 3.0, 4.2, 6.0, 9.0 or 13.2 mg MMH/kg bw/day) on days 6-13 of pregnancy, or as a single intragastric bolus (1 mg MMH/kg/bw or 5 mg MMH/kg/bw) on day 6 of pregnancy. Controls received corresponding amounts of saline. The average maternal serum concentrations, measured during the infusion treatment with a sensitive HPLC method, ranged from 0.072 micrograms MMH/ml (lowest dose) to 0.60 microgram MMH/ml (highest dose). The average serum levels measured 45 min after the intragastric application (peak levels) were 0.28 microgram MMH/ml and 1.6 microgram MMH/ml, respectively. Serum concentrations of MMH corresponding to those measured in the lower dose groups in this study were seen in pilot studies after a single mushroom meal in human volunteers. A dose-dependent, statistically significant increase in the number of resorptions was seen in all but the lowest dose group after the infusion of MMH. In addition, except for the two lowest doses, there was a dramatic, dose-dependent decrease in the pregnancy rate as compared to controls, with no pregnancies occurring at the two highest dose level groups. The decreased pregnancy rate was probably due to preimplantation loss which was shown to occur after a single intragastric bolus dose of MMH (5 mg/kg bw).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Effect of inhibitors of the FAD-containing monooxygenase system from rat liver microsomes on monomethylhydrazine metabolism and activation to reactive metabolites.

Several inhibitors of the FAD-containing monooxygenase (FAD-MO) system from rat liver microsomes (imipramine, chlorpromazine, mercaptoethylamine, dithiothreitol, naphthylthiourea, phenylthiocarbamide) and one inhibitor of the liver microsomal cytochrome P-450 (P-450)-mediated biotransformations (SKF 525 A), were tested as possible inhibitors of monomethylhydrazine (MMH) biotransformation to CO2 and to reactive metabolites that bind covalently to nucleic acids and proteins. Results confirm previous suggestions that both FAD-MO and P-450 are involved in MMH metabolism to CO2 and suggest a similar participation of both systems for production of reactive metabolites interacting with macromolecules.

Animals↗

Determination of hydrazine, monomethylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine by nonaqueous capillary electrophoresis with amperometric detection.

The present study is concerned with the application of nonaqueous capillary electrophoresis (NACE) with electrochemical detection (ED) to the separation and quantitative determination of hydrazine (Hy) and its methyl derivatives. The best performance of NACE-ED was found when using 4 mM sodium acetate/10 mM acetic acid/methanol: acetonitrile = 1:2 as the running buffer, with a bare platinum working electrode set at +1.0 V in an end-column amperometric detection cell. The choice and ratio of suitable solvents for the separation and injection media played an essential role for the performance characteristics of the method. The limits of detection for Hy, methylhydrazine, symmetrical dimethylhydrazine, and unsymmetrical dimethylhydrazine were 5, 2, 12, and 1 ng/mL, respectively. This is between one and two orders of magnitude lower than that achieved by previously reported CE-ED methods in aqueous buffer systems in conjunction with various types of chemically modified electrodes. The practical utility of the new NACE-ED methodology is demonstrated in terms of the determination of traces of Hys in spiked environmental samples containing a wide range of explosives and related compounds.

1,2-Dimethylhydrazine↗

Methylation of rat and mouse DNA by the mushroom poison gyromitrin and its metabolite monomethylhydrazine.

Consumption of false morel (Gyromitra esculenta Fr.) has been associated not only with acute poisoning, but also with a carcinogenic risk. The hydrolysis of acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin, the main toxic component of false morel) results in the formation of the methylating agents N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MMH) (by further hydrolysis of MFH). This study reports traces of N-7-methylguanine (N7MeGu) in liver DNA from mice and a rat treated with gyromitrin. After repeated administration of MMH, N7MeGu was identified in rat liver DNA. In mice exposed to MMH according to a dosing scheme identical to that reported to induce tumours in this species, O6-methylguanine was present in liver and kidney DNA. The results indicate that a relatively low carcinogenic risk is associated with false morel consumption. The risk may be greater in individuals with a decreased detoxification rate (acetylation) of MFH, in whom larger amounts of MMH are formed from gyromitrin.

Acetaldehyde↗