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Chemico-biological Interactions Oct 1986Ferric sigma-phenyl complexes of hemoglobin and liver cytochrome P-450 are formed in vivo upon administration of C6H5NHNH2 to rats. Small amounts of the sigma-methyl...
Ferric sigma-phenyl complexes of hemoglobin and liver cytochrome P-450 are formed in vivo upon administration of C6H5NHNH2 to rats. Small amounts of the sigma-methyl complex of hemoglobin were also detected in vivo upon treatment of rats with CH3NHNH2. At the doses used for CH3NHNH2 (25 and 50 mg/kg) the states and levels of hemoglobin in the blood and spleen, and of cytochrome P-450 in the liver were almost unchanged. On the contrary, C6H5NHNH2 (25-100 mg/kg) led to a decrease of the HbO2 blood level (10-50%), together with an increase in the HbFe(III) level and the appearance of the HbFe(III)-C6H5 complex. The concentration of this complex reaches its maximum value (2 mM) 1 h after C6H5NHNH2 administration (20% of total hemoglobin). At the same time large amounts of HbO2, HbFe(III) and HbFe(III)-C6H5 appeared in the spleen, and remained high up to 24 h after treatment. Treatment of rats with C6H5NHNH2 (25-100 mg/kg) led to a significant decrease in the level of liver cytochrome P-450 (a 70% decrease 2 h after treatment with 100 mg/kg C6H5NHNH2). About 15% of the remaining cytochrome P-450 existed as a cyt.-P-450-Fe(III)-C6H5 complex, a new example of cytochrome P-450-Fe-metabolite complex which is stable in vivo.
Topics: Animals; Cytochrome P-450 Enzyme System; Hemoglobins; Kinetics; Liver; Male; Methylhydrazines; Microsomes, Liver; Monomethylhydrazine; Phenobarbital; Phenylhydrazines; Protein Binding; Rats; Rats, Inbred Strains
PubMed: 3779881
DOI: 10.1016/0009-2797(86)90020-7 -
Archives of Toxicology May 1986Several inhibitors of the FAD-containing monooxygenase (FAD-MO) system from rat liver microsomes (imipramine, chlorpromazine, mercaptoethylamine, dithiothreitol,...
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.
Topics: Animals; Biotransformation; Cytochrome P-450 Enzyme System; Flavin-Adenine Dinucleotide; Male; Methylhydrazines; Microsomes, Liver; Mixed Function Oxygenases; Rats; Rats, Inbred Strains
PubMed: 3741147
DOI: 10.1007/BF00263961 -
Schweizerische Rundschau Fur Medizin... Sep 1985
Topics: Adult; Child; Critical Care; Humans; Methylhydrazines; Monomethylhydrazine; Mushroom Poisoning; Peritoneal Dialysis; Renal Dialysis
PubMed: 4059736
DOI: No ID Found -
Bulletin of Environmental Contamination... Jul 1985
Topics: Dose-Response Relationship, Drug; Eukaryota; Methylhydrazines; Monomethylhydrazine; Water Pollutants; Water Pollutants, Chemical
PubMed: 4027416
DOI: 10.1007/BF01636486 -
Analytical Chemistry Dec 1984
Topics: 1,2-Dimethylhydrazine; Air Pollutants, Occupational; Chemical Phenomena; Chemistry; Chromatography, Gas; Dimethylhydrazines; Drug Stability; Hydrazines; Methylhydrazines; Monomethylhydrazine
PubMed: 6524668
DOI: 10.1021/ac00278a074 -
The Medical Letter on Drugs and... Jul 1984
Topics: Aldehyde Oxidoreductases; Amanita; Basidiomycota; Hallucinogens; Humans; Monomethylhydrazine; Mushroom Poisoning; Mycotoxins; Parasympathomimetics; Peptides, Cyclic; Plants, Edible; Plants, Toxic
PubMed: 6539850
DOI: No ID Found -
Journal of Chromatography Apr 1984
Topics: Ascomycota; Methylhydrazines; Monomethylhydrazine; Mycotoxins; Spectrometry, Fluorescence
PubMed: 6725463
DOI: 10.1016/s0021-9673(01)87720-7 -
Agents and Actions Apr 1984N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human...
N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.
Topics: Amine Oxidase (Copper-Containing); Animals; Humans; Intestinal Mucosa; Intestines; Methylhydrazines; Monomethylhydrazine; Mutagens; Rabbits; Rats; Rats, Inbred Strains; Swine
PubMed: 6428190
DOI: 10.1007/BF01973825 -
Journal of Toxicology and Environmental... 1984The embryotoxicity and teratogenicity of methylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine were investigated with pregnant Fischer-344 rats. The...
The embryotoxicity and teratogenicity of methylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine were investigated with pregnant Fischer-344 rats. The compounds were administered ip on d 6-15 of pregnancy. A dose-dependent reduction in maternal weight gains occurred for all three compounds. A dose-related teratogenic effect did not occur for any of the three compounds. Embryotoxicity, manifested as reduced 20-d fetal weights, occurred only in the 1,1-dimethylhydrazine and 1,2-dimethylhydrazine high-dose treatment groups. The results indicate that none of the three methylated hydrazine derivatives are selectively embryotoxic or teratogenic in the rat.
Topics: 1,2-Dimethylhydrazine; Animals; Body Weight; Dimethylhydrazines; Female; Fetal Resorption; Injections, Intraperitoneal; Methylhydrazines; Monomethylhydrazine; Pregnancy; Rats; Rats, Inbred F344; Teratogens
PubMed: 6716510
DOI: 10.1080/15287398409530486 -
IARC Scientific Publications 1984N-Nitrosodimethylamine (NDMA) and two of its metabolites, monomethylhydrazine (MMH) and 1,1-dimethylhydrazine (UDMH) were metabolized to carbon dioxide by rat liver...
N-Nitrosodimethylamine (NDMA) and two of its metabolites, monomethylhydrazine (MMH) and 1,1-dimethylhydrazine (UDMH) were metabolized to carbon dioxide by rat liver slices. Under these conditions, NDMA and MMH, but not UDMH, produced reactive metabolites that bound covalently to nucleic acids. Rat liver microsomes or 9000 X g supernatants were able to transform NDMA, MMH and UDMH to formaldehyde. In the case of MMH and UDMH, enzymatic and non-enzymatic pathways of formaldehyde formation were present in both liver microsomes and 9000 X g supernatants. NDMA, MMH and UDMH led to covalent binding in incubation mixtures containing either microsomes or 9000 X g supernatants. In the case of NDMA, the process was enzymatic and required NADPH in both cellular fractions. In the case of MMH, the process was enzymatic in microsomes, and required NADPH and oxygen when using UDMH or MMH and 9000 X g supernatants; interactions of a non-enzymatic nature leading to covalent binding to proteins were dominant. These results suggest that part of the carbon dioxide produced during NDMA metabolism might derive from UDMH and MMH. Similarly, a significant part of the covalent binding of NDMA metabolites to proteins in incubation mixtures containing microsomes or 9000 X g supernatants might derive from enzymatic and non-enzymatic reactions of UDMH or MMH. Also, a minor part of the covalent binding of NDMA reactive metabolites to nucleic acids might be due to further biotransformation of MMH to reactive metabolites. It may be concluded from the present results that biotransformation of NDMA to UDMH and MMH might not be a detoxication process, as previously thought, but one related to some of the toxic effects of NDMA.
Topics: Animals; Biotransformation; Carbon Dioxide; Dimethylhydrazines; Dimethylnitrosamine; Formaldehyde; Male; Methylhydrazines; Microsomes, Liver; Oxidation-Reduction; Rats; Rats, Inbred Strains
PubMed: 6442710
DOI: No ID Found