scholarly journals Acetylene, a mammalian metabolite of 1,1,1-trichloroethane

1992 ◽  
Vol 286 (2) ◽  
pp. 353-356 ◽  
Author(s):  
H Dürk ◽  
J L Poyer ◽  
C Klessen ◽  
H Frank
Keyword(s):  
Acute Toxicity ◽  
Rat Liver ◽  
Trichloroacetic Acid ◽  
Spin Trapping ◽  
Radical Intermediate ◽  
Cytochrome P 450

1,1,1-Trichloroethane (TCE) is a widely used industrial solvent of low acute toxicity. It is slowly oxidized to trichloroethanol and trichloroacetic acid by cytochrome P-450-dependent mono-oxygenases. Increased inhalative uptake by rats under hypoxia and spin-trapping experiments indicate that TCE is also reductively metabolized to a radical intermediate. Acetylene is formed as a metabolite, suggesting transfer of an additional electron to form the corresponding carbene. Hypoxia and induction of mixed-function mono-oxygenases accelerate the formation of acetylene. Experiments performed in vitro with rat liver microsomal fractions yield analogous results.

Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers

1997 ◽  
Vol 16 (3) ◽  
pp. 131-137 ◽  
Author(s):  
Sarah J Crosbie ◽  
PG Blain ◽  
Faith M Williams
Keyword(s):  
Skeletal Muscle ◽  
Rat Liver ◽  
Fold Increase ◽  
Rat Tissues ◽  
Human Cytochrome ◽  
Extrahepatic Tissues ◽  
Mass Spectometry ◽  
Fast Twitch ◽  
Cytochrome P 450

1 The in vitro metabolism ofn-hexane was studied in rat liver, lung, brain and skeletal muscle microsomes and in microsomes prepared from cell lines expressing human cytochrome P-450 2E1 or 2B6. The hydro xylated metabolites ofn-hexane were quantified by gas chromatography-mass spectometry. 2 Rat liver and extensor digitorum longus (EDL, fast- twitch skeletal muscle) microsomes and the CYP 2B6 microsomes produced the pre-neurotoxic metabolite of n-hexane, 2-hexanol as a major metabolite in contrast to the other rat tissues examined. 3 Inhibition of 2- and 3-hexanol production from n- hexane by rat lung microsomes using metyrapone, an inhibitor of cytochrome P-450 2B1 activity, resulted in almost complete inhibition of lung microsomal activ ity. 4 Production of all three hexanols was significantly increased with phenobarbital-induced rat liver micro somes, with a 10-fold increase in 2- and 3-hexanol production. A slight increase in 2-hexanol production with phenobarbital-induced rat EDL and brain micro somes was observed. No increase in n-hexane meta bolism was noted following induction with β- naphthoflavone or with ethanol.

Carcinogenic Non-Aminoazo Dye 1-Phenylazo-2-hydroxynaphthalene (Sudan I) Is Oxidized by Rat Liver Microsomal Cytochrome P-450 to Metabolites Binding to Macromolecules (Nucleic Acids and Proteins)

1992 ◽  
Vol 57 (7) ◽  
pp. 1537-1546 ◽  
Author(s):  
Marie Stiborová ◽  
Pavel Anzenbacher
Keyword(s):  
Nucleic Acids ◽  
Rat Liver ◽  
Chemical Carcinogenesis ◽  
Reactive Metabolites ◽  
Reactive Metabolite ◽  
Microsomal Cytochrome ◽  
Sudan I ◽  
Cytochrome P 450

Carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I) is oxidized by microsomal cytochromes P-450 to reactive metabolite(s) binding to macromolecules (nucleic acids, proteins) in vitro. The extent of binding to macromolecules proceeded in the order: protein > rRNA > tRNA > DNA. The patern of products formed from Sudan I and binding of the reactive metabolites of this compound to macromolecules are dependent on the concentration of Sudan I, NADPH and on the duration of the incubation. The participation of the adducts formed with macromolecules in the initiation of chemical carcinogenesis is discussed.

scholarly journals Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide

1980 ◽  
Vol 186 (3) ◽  
pp. 763-772 ◽  
Author(s):  
A A B Badawy ◽  
C J Morgan
Keyword(s):  
Rat Liver ◽  
Activity Maximum ◽  
Haem Biosynthesis ◽  
Hexobarbital Sleeping Time ◽  
Tryptophan Pyrrolase ◽  
Liver Homogenates ◽  
The Relationship ◽  
Cytochrome P 450 ◽  
Phenazine Methosulphate

Rat liver tryptophan pyrrolase haem is maximally depleted at 30 min after administration of a 400 mg/kg dose of 2-allyl-2-isopropylacetamide. This depletion lasts for 24 h, by which time 5-aminoleevulinate synthase activity becomes maximally enhanced. 2. though the above maximum depletion of pyrrolase haem (at 0.5h) is also produced by a 100 mg/kg dose of the porphyrogen, this does not enhance synthase activity at 24 h. It and smaller doses, however, cause a smaller but earlier enhancement of synthase activity (maximum at 2 h) and produce a similarly short-lived deplation of pyrrolase haem. 3. The depletion of pyrrolase haem and the enhancement of synthase activity by the porphyrogen are inhibited by compound SKF 525-A and phenazine methosulphate, and are potentiated by nicotinamide but not by phenobarbitone. Phenazine methosulphate and nicotinamide also exert opposite effects on hexobarbital sleeping-time. 4. 2-Allyl-2-isopropylacetamde also the depletes pyrrolase haem in vitro. It does so in liver homogenates of control rats in the presence, and in those of phenobarbitone-treated rats in the absence of added NADPH. 5. A discussion of the present results in relation to previous work with other haemoproteins suggests that, whereas cytochrome P-450 (haem) is primarily involved in the production of the active (porphyrogenic) metabolite(s) of 2-allyl-2-isopropylacetamide, the haem pool used by tryptophan pyrrolase may play an important role in the effects of this compound on haem biosynthesis.

scholarly journals Phenylhydrazine-mediated induction of haem oxygenase activity in rat liver and kidney and development of hyperbilirubinaemia. Inhibition by zinc-protoporphyrin

1984 ◽  
Vol 217 (2) ◽  
pp. 409-417 ◽  
Author(s):  
M D Maines ◽  
J C Veltman
Keyword(s):  
Rat Liver ◽  
Zinc Protoporphyrin ◽  
Serum Total Bilirubin ◽  
Potent Inducer ◽  
Oxygenase Activity ◽  
Liver And Kidney ◽  
Haem Oxygenase ◽  
Cytochrome P 450

Phenylhydrazine was found to be a potent inducer of microsomal haem oxygenase activity in rat liver and kidney, but not in spleen. The phenylhydrazine-mediated increase in haem oxygenase activity was time-dependent. Maximum activity was attained 12h after treatment in the liver, and 24h after treatment in the kidney. The increases in the activity of haem oxygenase in the liver and the kidney could be inhibited by cycloheximide. Furthermore, the increases could not be elicited by the treatment of microsomal preparations in vitro with phenylhydrazine. In consonance with the increased haem oxygenase activity, a marked increase (16-fold) was observed in the serum total bilirubin concentration in phenylhydrazine-treated rats. The mechanism of haem degradation promoted by phenylhydrazine in vivo appears to differ from that in vitro; only in the former case is bilirubin formed as the end-product of haem degradation. When rats were given zinc-protoporphyrin (40 mumol/kg) 12h before and after phenylhydrazine treatment, the phenylhydrazine-mediated increases in haem oxygenase activity in the liver and the kidney were effectively blocked. Treatment of rats in vivo with the metalloporphyrin also inhibited the activity of splenic haem oxygenase, and promoted a major decrease in the serum bilirubin levels. In phenylhydrazine-treated animals, the microsomal content of cytochrome P-450 was significantly decreased in the absence of a decrease in the microsomal haem concentration. The decrease in cytochrome P-450 content was accompanied by an increased absorption in the 420nm region of the reduced CO-difference spectrum, suggesting the conversion of the cytochrome to an inactive form. The marked depletion of cellular glutathione levels suggests that this conversion may be related to the action of active intermediates and free radicals formed in the course of the interaction of phenylhydrazine with the haem moiety of cytochrome P-450.

Incorporation of cholesterol in vitro into rat liver microsomal fractions from serum and its effect on cytochrome P-450-dependent hydroxylation

1980 ◽  
Vol 8 (1) ◽  
pp. 122-123 ◽  
Author(s):  
PETER W. H. RAE ◽  
HENRY A. F. BLAIR ◽  
GEORGE S. BOYD ◽  
KEITH E. SUCKLING
Keyword(s):  
Rat Liver ◽  
Cytochrome P 450
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