scholarly journals The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used

1971 ◽  
Vol 123 (5) ◽  
pp. 805-814 ◽  
Author(s):  
T. F. Slater ◽  
B. C. Sawyer
Keyword(s):  
Lipid Peroxidation ◽  
Endoplasmic Reticulum ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Lipid Peroxides ◽  
Square Root ◽  
Microsomal Membranes ◽  
Stimulation Of ◽  
Homolytic Dissociation

1. The general features of the reaction by which carbon tetrachloride stimulates lipid peroxidation have been elucidated in rat liver microsomal suspensions and in mixtures of microsomes plus cell sap. The production of lipid peroxides has been correlated with malonaldehyde production in the systems used. 2. The stimulation of malonaldehyde production by carbon tetrachloride requires a source of reduced NADP+ and is dependent on the extent of the endogenous peroxidation of the microsomal membranes: if extensive endogenous peroxidation occurs during incubation then no stimulation by carbon tetrachloride is apparent. 3. The stimulation of malonaldehyde production by carbon tetrachloride has been shown to be proportional to the square root of the carbon tetrachloride concentration in the incubation mixture. It is concluded that the stimulation of malonaldehyde production by carbon tetrachloride results from an initiation process that is itself dependent on the homolytic dissociation of carbon tetrachloride to free-radical products. 4. The increased production of malonaldehyde due to carbon tetrachloride is accompanied by a decreased activity of glucose 6-phosphatase in rat liver microsomal suspensions. 5. The relative activities of bromotrichloromethane, fluorotrichloromethane and chloroform have been evaluated in comparison with the effects of carbon tetrachloride in increasing malonaldehyde production and in decreasing glucose 6-phosphatase activity. Bromotrichloromethane was more effective, and fluorotrichloromethane and chloroform were less effective, than carbon tetrachloride in producing these two effects. It is concluded that homolytic bond fission of the halogenomethanes is a requisite for the occurrence of the two effects observed in the endoplasmic reticulum.

scholarly journals A sub-population of rat liver membrane-bound ribosomes that are detached in vitro by carcinogens and centrifugation

1978 ◽  
Vol 176 (1) ◽  
pp. 9-14 ◽  
Author(s):  
D N Palmer ◽  
B R Rabin ◽  
D J Williams
Keyword(s):  
Lipid Peroxidation ◽  
Endoplasmic Reticulum ◽  
Rat Liver ◽  
Chemical Carcinogen ◽  
Centrifugal Forces ◽  
In Vitro Incubation ◽  
Liver Membrane ◽  
Membrane Bound

The chemical-carcinogen-induced detachment of ribosomes from rat liver endoplasmic reticulum was studied in vitro. Incubation of postmitochondrial supernatant with 0.2 mM-diethylnitrosamine or N-2-acetylaminofluorene removed approx. 16% of membrane-bound ribosomes, measured as differences in RNA/protein values of membrane separated from unbound ribosomes by flotation. These ribosomes are also detached by exposure to high centrifugal forces (160000g) and are among those removed by NADPH-catalysed lipid peroxidation. Extensive lipid peroxidation prohibits any measurement. The ribosomes (polyribosomes) removed are not those detached from the membrane by exposure to high KC1 concentrations (loosely bound) or high KC1 concentrations in the presence of puromycin (tightly bound). It is concluded then that centrifugally labile and carcinogen-sensitive represent a previously unreported sub-population of membrane-bound ribosomes.

scholarly journals The inhibitory effects in vitro of phenothiazines and other drugs on lipid-peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride

1968 ◽  
Vol 106 (1) ◽  
pp. 155-160 ◽  
Author(s):  
T F Slater
Keyword(s):  
Lipid Peroxidation ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Protective Agent ◽  
Liver Necrosis ◽  
Inhibitory Effects

1. The effects of several phenothiazine derivatives on lipid-peroxidation systems in rat liver microsomes were studied and the results are considered in relation to the hepatotoxic action of carbon tetrachloride. 2. The lipid-peroxidation system coupled to NADPH2 oxidation and stimulated by an ADP–Fe2+ mixture is strongly inhibited in vitro by promethazine (50% inhibition at 29μm). Chlorpromazine and Stelazine also inhibit the peroxidation system but are less effective than promethazine. 3. The effects of promethazine on three other systems involving oxygen uptake (sulphite oxidation, orcinol oxidation and mitochondrial succinate oxidation) were also studied. Promethazine does not inhibit these systems to the same extent as it does the NADPH2–ADP–Fe2+ lipid-peroxidation system. 4. Promethazine also produces an inhibition of the NADPH2–ADP–Fe2+ system in liver microsomes after administration in vivo. It is concluded that the inhibition involves the interaction of the drug (or a metabolite of it) with the microsomal electron-transport chain. 5. Several other compounds known to protect the rat against liver necrosis after the administration of carbon tetrachloride were tested for inhibitory action on the NADPH2–ADP–Fe2+ system. No clear correlation was observed between effectiveness in vivo as a protective agent and inhibitory effects on the NADPH2–ADP–Fe2+ system in vitro. 6. Promethazine was found to inhibit the stimulation of lipid peroxidation produced in rat liver microsomes by low concentrations of carbon tetrachloride. This effect occurs at a concentration similar to that observed in vivo after administration of a normal clinical dose.

scholarly journals Vitamin E and hepatotoxic agents

1969 ◽  
Vol 23 (2) ◽  
pp. 297-307 ◽  
Author(s):  
J. Green ◽  
J. Bunyan ◽  
M. A. Cawthorne ◽  
A. T. Diplock
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Rat Liver ◽  
Protective Action ◽  
Lipid Peroxides ◽  
Ultraviolet Region ◽  
Intraperitoneal Dose ◽  
And Control

1. It has been suggested that carbon tetrachloride damages rat liver by accelerating processes of lipid peroxidation at subcellular sites and that the protective action of vitamin E is due to its functioning as an antioxidant in vivo. Direct evidence for these mechanisms in vivo has been sought and is critically examined.2. The increased production of malondialdehyde by rat liver microsomal fractions during incubation with CCl4 was shown to be a function of the vitamin E status of the rat and of an in vitro reaction, which could not be correlated with the hepatotoxic action of CCI4.3. Evidence for the production of lipid peroxides by CCl4 in the livers of vitamin E-deficient and vitamin E-supplemented rats was sought (I) by measurement of ultraviolet spectral changes ('diene' formation) and (2) by direct micro-iodimetric determination of the peroxide. No differences in peroxide content were found between CC14-treated and control rats, nor were the spectrophotometric changes in the ultraviolet region related to the presence of vitamin E.4. The effect of CCI4 (2.0 ml/kg orally) on ATP levels in rat liver was studied at intervals from 3 to 68 h. The primary lesion leading to necrosis and fat accumulation after CCl4 treatment occurred many hours before the eventual slight decline in ATP. Although the levels of ATP were somewhat higher in vitamin E-deficient rats, vitamin E did not prevent the slight decline in ATP that took place. Since ATP is known to be highly sensitive to peroxidation, the results suggest that lipid peroxidation is not the primary event in CCl4 poisoning.5. The effect of CC14on the metabolism of [14C]D-α-tocopherol in the rat was studied. A single intraperitoneal dose of CCl4 (2.0 m/kg) did not increase the destruction of α-tocopherol in the liver or carcass after 24 h. Three smaller daily doses of CC14 (0.25 ml/kg) also did not increase α-tocopherol catabolism; on the contrary, significantly more α-tocopherol was found in the livers of rats treated with CCI4. These results suggest that CCl4 does not increase lipid peroxidation in vivo.

scholarly journals The stimulatory effects of carbon tetrachloride on peroxidative reactions in rat liver fractions in vitro. Inhibitory effects of free-radical scavengers and other agents

1971 ◽  
Vol 123 (5) ◽  
pp. 823-828 ◽  
Author(s):  
T. F. Slater ◽  
B. C. Sawyer
Keyword(s):  
Free Radical ◽  
Vitamin E ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Stimulation Of

1. The effects of a number of free-radical scavengers and other agents on the stimulation of malonaldehyde production due to low concentrations of carbon tetrachloride have been studied in rat liver microsome suspensions. 2. Promethazine, propyl gallate and NN′-diphenyl-p-phenylenediamine were extremely active in inhibiting the stimulation of malonaldehyde production due to carbon tetrachloride; inhibitory effects were demonstrable with these agents at 0.1μm. 3. Low concentrations (1–100nm) of vitamin E–polyethylene glycol 1000–succinate increased the stimulation of malonaldehyde production due to carbon tetrachloride, but higher concentrations of the vitamin E preparation decreased both the stimulation due to carbon tetrachloride and the endogenous peroxidation that occurs in the absence of carbon tetrachloride. 4. Other agents tested that were effective in the range 1–20μm in decreasing the stimulation of malonaldehyde production due to carbon tetrachloride were inosine, desferrioxamine and EDTA. Agents tested that were not effective, except at very high concentrations (100μm or greater), were Nupercaine, Cetab and sodium phenobarbitone. 5. The results are discussed in terms of the mechanisms responsible for the observed inhibitions of malonaldehyde production, and of the relevance of the in vitro system to the liver damage produced by carbon tetrachloride in vivo.

Isolation and expression of cDNA clones for a rat liver asialoglycoprotein receptor

1986 ◽  
Vol 6 (6) ◽  
pp. 527-534
Author(s):  
Colin Watts
Keyword(s):  
Rat Liver ◽  
Protein Sequence ◽  
Wheat Germ ◽  
Asialoglycoprotein Receptor ◽  
Cdna Clones ◽  
Oligonucleotide Probes ◽  
Synthetic Oligonucleotide ◽  
Microsomal Membranes ◽  
Synthetic Oligonucleotides

cDNA clones for the major rat liver asialoglycoprotein (ASGP) receptor were isolated from a phage λgtl 1 library using synthetic oligonucleotide probes corresponding to two regions of the protein sequence. The longest clone obtained encoded all but the first 11 codons of the receptor. The cDNA was completed with synthetic oligonucleotides and was used to direct the synthesis of mRNA for the receptor in vitro. Subsequent translation in a wheat germ lysate produced authentic ASGP receptor which assembled correctly into microsomal membranes.

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