Cytochrome P-450-dependent covalent binding of carbon disulfide to rat liver microsomal protein in vitro and its prevention by reduced glutathione

1987 ◽  
Vol 61 (2) ◽  
pp. 155-157 ◽  
Author(s):  
R. R. Dalvi
Keyword(s):  
Rat Liver ◽  
Carbon Disulfide ◽  
Reduced Glutathione ◽  
Covalent Binding ◽  
Microsomal Protein ◽  
Cytochrome P 450

scholarly journals Reduced glutathione protection against rat liver microsomal injury by carbon tetrachloride. Dependence on O2

1983 ◽  
Vol 215 (3) ◽  
pp. 441-445 ◽  
Author(s):  
R F Burk ◽  
K Patel ◽  
J M Lane
Keyword(s):  
Lipid Peroxidation ◽  
Free Radicals ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Reduced Glutathione ◽  
Covalent Binding ◽  
Microsomal Protein ◽  
Protective Mechanism ◽  
Cytochrome P 450 ◽  
Dependent Mechanism

Rat liver microsomal membranes contain a reduced-glutathione-dependent protein(s) that inhibits lipid peroxidation in the ascorbate/iron microsomal lipid peroxidation system. It appears to exert its protective effect by scavenging free radicals. The present work was carried out to assess the effect of this reduced-glutathione-dependent mechanism on carbon tetrachloride-induced microsomal injury and on carbon tetrachloride metabolism because they are known to involve free radicals. Rat liver microsomes were incubated at 37 degrees C with NADPH, EDTA and carbon tetrachloride. The addition of 1 mM-reduced glutathione (GSH) markedly inhibited lipid peroxidation and glucose 6-phosphatase inactivation and, to a lesser extent, inhibited cytochrome P-450 destruction. GSH also inhibited covalent binding of [14C]carbon tetrachloride-derived 14C to microsomal protein. These results indicate that a GSH-dependent mechanism functions to protect the microsomal membrane against free-radical injury in the carbon tetrachloride system as well as in the iron-based systems. Under anaerobic conditions, GSH had no effect on chloroform formation, carbon tetrachloride-induced destruction of cytochrome P-450 or covalent binding of [14C]carbon tetrachloride-derived 14C to microsomal protein. Thus, the GSH protective mechanism appears to be O2-dependent. This suggests that it may be specific for O2-based free radicals. This O2-dependent GSH protective mechanism may partly underlie the observed protection of hyperbaric O2 against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity.

scholarly journals Metabolic activation of acetylenic substituents to derivatives in the rat causing the loss of hepatic cytochrome P-450 and haem

1978 ◽  
Vol 174 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Ian N. H. White
Keyword(s):  
Covalent Binding ◽  
Metabolic Activation ◽  
Microsomal Protein ◽  
Significant Loss ◽  
Microsomal Cytochrome ◽  
Rf Values ◽  
Green Pigments ◽  
Cytochrome P 450

1. A number of acetylenic-substituted steroidal and non-steroidal compounds, including 2,2-dipropargylacetamide, pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol (Danazol) and acetylene gas, when administered to rats in vivo brought about a decrease in the concentrations of hepatic microsomal cytochrome P-450 and haem. Abnormal haem-breakdown products, ‘green pigments’, and porphyrins accumulated in the livers of these animals. 2. For loss of microsomal cytochrome P-450 to occur in vitro, metabolic activation of the acetylenic substituent was necessary. The enzyme system responsible required NADPH and air, and was induced by pretreatment of rats with phenobarbitone; these are characteristics typical of the microsomal mixed-function oxidases. 3. When rats were dosed with 17α-ethynyl-17β-hydroxyandrost-4-en-3-one (ethynyltestosterone, 1mmol/kg) the pattern of green pigments extracted from the liver 4h after dosing and separated by t.l.c. was quite different from that in rats given 17β-hydroxy-17α-vinylandrost-4-en-3-one (vinyltestosterone), suggesting that reduction of the unsaturated triple bond to a double bond is not normally part of the metabolic activation pathway of the acetylenic substituent. 4. The green pigments extracted from the livers of rats 4h after the administration of the acetylenic-substituted compounds (1mmol/kg) when separated by silica-gel t.l.c. had variable RF values. The number and distribution of green pigments was characteristic for each compound examined. There was little correlation between the total loss of hepatic microsomal haem and the apparent intensity of the green pigments seen on the thin-layer chromatograms. 5. After incubation of [14C]acetylene in vitro with microsomal preparations from phenobarbitone-pretreated rats and a NADPH-generating system, no significant covalent binding to microsomal protein was detected over a 30min incubation period, although under similar conditions there was a significant loss of cytochrome P-450.

The covalent binding of cyclosporin a to rat liver macromolecules in vivo and in vitro: The role of cytochrome P-450

Toxicology ◽  
1987 ◽  
Vol 47 (3) ◽  
pp. 277-284 ◽  
Author(s):  
J. Fred Nagelkerke ◽  
Roeline B. Tijidens ◽  
Erik P. Schwarz ◽  
Marjolein F.G. Winters ◽  
Leendert C. Paul ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Rat Liver ◽  
Covalent Binding ◽  
Cytochrome P 450

COVALENT BINDING OF STYRENE OXIDE TO RAT LIVER MACROMOLECULES IN VIVO AND IN VITRO

1977 ◽  
pp. 698-702 ◽  
Author(s):  
Jukka Marniemi ◽  
Else-Maj Suolinna ◽  
Niilo Kaartinen ◽  
Harri Vainio
Keyword(s):  
Rat Liver ◽  
Styrene Oxide ◽  
Covalent Binding

The role of metabolic activation by cytochrome P-450 in covalent binding of VP 16-213 to rat liver and HeLa cell microsomal proteins

1985 ◽  
Vol 21 (9) ◽  
pp. 1099-1106 ◽  
Author(s):  
J.M.S. van Maanen ◽  
C. de Ruiter ◽  
J. de Vries ◽  
P.R. Kootstra ◽  
F. Gobas ◽  
...  
Keyword(s):  
Hela Cell ◽  
Rat Liver ◽  
Covalent Binding ◽  
Metabolic Activation ◽  
Cytochrome P 450

Covalent binding of carbaryl (1-naphthyl-N-ethylcarbamate) to rat liver microsomes in vitro

1979 ◽  
Vol 24 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Alexander Miller ◽  
Marilyn C. Henderson ◽  
Donald R. Buhler
Keyword(s):  
Rat Liver ◽  
Covalent Binding ◽  
Liver Microsomes ◽  
Rat Liver Microsomes
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