EFFECTS OF ALIPHATIC ALCOHOLS ON THE METABOLISM OF GLUCOSE AND FRUCTOSE IN RAT LIVER SLICES

1963 ◽  
Vol 41 (3) ◽  
pp. 793-803 ◽  
Author(s):  
Edward Majchrowicz ◽  
J. H. Quastel
Keyword(s):  
Rat Liver ◽  
Liver Slice ◽  
Inhibitory Effect ◽  
Aliphatic Alcohols ◽  
Isotopic Dilution ◽  
Acetyl Coa ◽  
Radioactive Carbon ◽  
Liver Slices ◽  
The Difference ◽  
Ethanol Ethanol

Ethanol, at concentrations up to 3 mM, whilst having little inhibitory effect on the production of respiratory CO2of rat liver slices, has a marked suppressing action on the formation of labelled CO2from labelled glucose. The suppression of C14O2formation by ethanol from radioactive glucose is independent of the concentration of the latter and amounts to 57% with 3 mM ethanol after 1 hour's incubation. The results are consistent with the conclusion that ethanol gives rise more rapidly than glucose to acetyl CoA and that the large suppressing action of ethanol in rat liver slices is due to isotopic dilution of labelled acetyl CoA derived from the labelled sugars with the unlabelled acetyl CoA derived from ethanol. Ethanol exercises a larger inhibition of the rate of C14O2formation from glucose-6-C14than from glucose-1-C14. The difference between the effects of ethanol on C14O2formation from glucose-1-C14and glucose-6-C14is presumably due to operation of the hexosemonophosphate shunt.The higher aliphatic alcohols have about the same diminishing effect on C14O2formation from glucose-U-C14and fructose-U-C14as does ethanol. This observation may also be a consequence of dilution of labelled acetyl CoA derived from the sugars by unlabelled acetyl CoA coming from the added alcohol. Incorporation of radioactive carbon from the labelled sugars into liver proteins and lipids is inhibited by ethanol and higher aliphatic alcohols, and the inhibitions are similar in magnitude to those of C14O2formation. These may be accounted for by isotopic dilution. The amounts of C14incorporated into lipids and proteins from radioactive glucose and fructose are small, being about 1/10th of that appearing in the CO2.The higher aliphatic alcohols suppress total CO2formation during rat liver slice respiration much more than does ethanol at equivalent concentrations.

EFFECTS OF ALIPHATIC ALCOHOLS ON THE METABOLISM OF GLUCOSE AND FRUCTOSE IN RAT LIVER SLICES

1963 ◽  
Vol 41 (1) ◽  
pp. 793-803 ◽  
Author(s):  
Edward Majchrowicz ◽  
J. H. Quastel
Keyword(s):  
Rat Liver ◽  
Liver Slice ◽  
Inhibitory Effect ◽  
Aliphatic Alcohols ◽  
Isotopic Dilution ◽  
Acetyl Coa ◽  
Radioactive Carbon ◽  
Liver Slices ◽  
The Difference ◽  
Ethanol Ethanol

Ethanol, at concentrations up to 3 mM, whilst having little inhibitory effect on the production of respiratory CO2of rat liver slices, has a marked suppressing action on the formation of labelled CO2from labelled glucose. The suppression of C14O2formation by ethanol from radioactive glucose is independent of the concentration of the latter and amounts to 57% with 3 mM ethanol after 1 hour's incubation. The results are consistent with the conclusion that ethanol gives rise more rapidly than glucose to acetyl CoA and that the large suppressing action of ethanol in rat liver slices is due to isotopic dilution of labelled acetyl CoA derived from the labelled sugars with the unlabelled acetyl CoA derived from ethanol. Ethanol exercises a larger inhibition of the rate of C14O2formation from glucose-6-C14than from glucose-1-C14. The difference between the effects of ethanol on C14O2formation from glucose-1-C14and glucose-6-C14is presumably due to operation of the hexosemonophosphate shunt.The higher aliphatic alcohols have about the same diminishing effect on C14O2formation from glucose-U-C14and fructose-U-C14as does ethanol. This observation may also be a consequence of dilution of labelled acetyl CoA derived from the sugars by unlabelled acetyl CoA coming from the added alcohol. Incorporation of radioactive carbon from the labelled sugars into liver proteins and lipids is inhibited by ethanol and higher aliphatic alcohols, and the inhibitions are similar in magnitude to those of C14O2formation. These may be accounted for by isotopic dilution. The amounts of C14incorporated into lipids and proteins from radioactive glucose and fructose are small, being about 1/10th of that appearing in the CO2.The higher aliphatic alcohols suppress total CO2formation during rat liver slice respiration much more than does ethanol at equivalent concentrations.

EFFECTS OF ALIPHATIC ALCOHOLS AND FATTY ACIDS ON THE METABOLISM OF ACETATE BY RAT LIVER SLICES

1961 ◽  
Vol 39 (12) ◽  
pp. 1895-1909 ◽  
Author(s):  
E. Majchrowicz ◽  
J. H. Quastel
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Acid Synthesis ◽  
Aliphatic Alcohols ◽  
Isotopic Dilution ◽  
Acetate Oxidation ◽  
Inhibitory Effects ◽  
Acetyl Coa ◽  
Liver Slices ◽  
Equivalent Quantity

The effects of the addition of normal aliphatic alcohols and fatty acids on the metabolism of acetate by rat liver slices have been investigated, with particular reference to the formation, from acetate-1-C14, of C14O2 and radioactive lipids, proteins, and fatty acids. Whereas the addition of unlabelled acetate causes a fall in the rate of formation of C14O2, the decrease, at low concentrations, is less than that calculated for isotopic dilution. This is probably due to the fact that with an increased concentration of acetate there is an increased rate of acetate oxidation. However, the addition of ethanol causes a larger fall in the rate of formation of C14O2 than would be expected if the alcohol were converted to acetate. This points to some inhibition by ethanol of acetate oxidation, a conclusion borne out by the inhibitory effects of n-alcohols on total CO2 formation (in the absence and in the presence of added acetate) by rat liver slices. The fact, however, that the inhibitory effect of ethanol reaches a maximum at 5 mmolar and is constant to 50 mmolar points against a major inhibition due to ethanol per se. The results would be consistent with the conclusion that ethanol, at low concentrations, is more quickly converted into acetyl-CoA than acetate itself and that its speed of conversion into acetyl-CoA reaches a maximum at about 5 mmolar with rat liver slices. n-Propanol is much more inhibitory than ethanol but its effect is quantitatively identical with that of an equivalent quantity of propionate. Propionate and n-propanol are presumably rapidly converted to propionyl-CoA (or methyl malonyl-CoA), which is the effective inhibitor of acetate oxidation by its competition with acetyl-CoA. Propanol also shows direct inhibitory effects on acetate oxidation in rat liver slices. n-Butanol, n-pentanol, and n-hexanol have inhibitory effects identical with those of equivalent concentrations of corresponding fatty acids. These facts point to the oxidation, in rat liver, of aliphatic alcohols and fatty acids to propionyl-CoA or acetyl-CoA which inhibit C14O2 formation from acetate-1-C14 by competition or isotopic dilution. Alternations of inhibition occur between the odd- and even-numbered carbon alcohols and fatty acids which may be explained by the formation of mixtures of acetyl-CoA and the highly inhibitory propionyl-CoA from the long-chain alcohols and acids. Tribromoethanol is less inhibitory than propanol at equivalent concentrations though it is an effective inhibitor of acetate oxidation. Allyl alcohol is a much more potent inhibitor. Ethanol inhibits incorporation of radioactivity of acetate-1-C14 into fatty acids in rat liver, the inhibition being approximately equal to, or possibly less than, that due to an equivalent quantity of acetate. This may be explained on the basis of isotopic dilution, by acetyl-CoA derived from the alcohol, with radioactive acetyl-CoA undergoing synthesis to radioactive fatty acids. Thus ethanol, at the concentrations investigated, by taking part in fatty acid synthesis, inhibits acetate conversion to fatty acids. Glucose shows the largest effect in stimulating fatty acid synthesis in the liver from acetate, fructose is less effective, and sorbitol shows no effect. The aliphatic alcohols inhibit incorporation of radioactivity from acetate-1-C14 into liver lipids and proteins, propanol and pentanol showing the largest effects. There is an alternation between odd- and even-numbered aliphatic chains. The disappearance, or utilization, of acetate by rat liver slices is inhibited by the aliphatic alcohols, alternations between the odd- and even-numbered chains again being observable. The results are explained as being partly due to isotopic dilution and competition by acetyl-CoA and propionyl-CoA, and partly due to suppressions of acetate metabolism by the alcohols.

scholarly journals Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives

1975 ◽  
Vol 148 (3) ◽  
pp. 461-469 ◽  
Author(s):  
D N Brindley ◽  
M Bowley
Keyword(s):  
Rat Liver ◽  
Inhibitory Effect ◽  
Diacylglycerol Acyltransferase ◽  
Major Effect ◽  
Glycerol Phosphate ◽  
Liver Slices ◽  
Phosphatidate Phosphohydrolase ◽  
Marked Accumulation ◽  
Glycerolipid Synthesis ◽  
Phosphatidylcholine Synthesis

The effects on glycerolipid synthesis of a series of compounds including many drugs were investigated in cell-free preparations and slices of rat liver. p-Chlorobenzoate, p-chlorophenoxyisobutyrate, halofenate, D-amphetamine, adrenaline, procaine and N-[2-(4-chloro-3-sulphamoylbenzoyloxy)ethyl]norfenfluramine had little inhibitory effect on any of the systems investigated. Two amphiphilic anions, clofenapate and 2-(p-chlorophenyl)-2-(m-trifluoromethylphenoxy)acetate, both inhibited glycerol phosphate acyltransferase and diacylglycerol acyltransferase at approx. 1.6 and 0.7 mm respectively. Clofenapate (1 mm) also inhibited the incorporation of glycerol into lipids by rat liver slices without altering the relative proportions of the different lipids synthesized. The amphilic amines, mepyramine, fenfluramine, norfenfluramine, hydroxyethylnorfenfluramine, N-(2-benzoyloxyethyl)norfenfluramine, cinchocaine, chlorpromazine and demethylimipramine inhibited phosphatidate phosphohydrolase by 50% at concentrations between 0.2 and 0.9 mm. The last four compounds inhibited glycerol phosphate acyltransferase by 50% at concentrations between 1 and 2.6 mm. None of the amines examined appeared to be an effective inhibitor of diacylglycerol acyltransferase. Norfenfluramine, hydroxyethylnorfenfluramine and N-(2-benzoyloxyethyl)norfenfluramine produced less inhibition of glycerol incorporation into total lipids than was observed with equimolar clofenapate. The major effect of these amines in liver slices was to inhibit triacylglycerol and phosphatidylcholine synthesis and to produce a marked accumulation of phosphatidate. The results are discussed in terms of the control of glycerolipid synthesis. They partly explain the observed effects of the various drugs on lipid metabolism. The possible use of these compounds as biochemical tools with which to investigate the reactions of glycerolipid synthesis is considered.

scholarly journals Influence of some aliphatic alcohols on the metabolism of rat liver slices

1967 ◽  
Vol 105 (1) ◽  
pp. 93-97 ◽  
Author(s):  
Olof A. Forsander
Keyword(s):  
Carbon Dioxide ◽  
Oxygen Uptake ◽  
Rat Liver ◽  
Marked Effect ◽  
Tricarboxylic Acid Cycle ◽  
Carbon Dioxide Production ◽  
Aliphatic Alcohols ◽  
Liver Alcohol Dehydrogenase ◽  
Liver Slices ◽  
Lactate And Pyruvate

The influence of some aliphatic alcohols on oxygen uptake, carbon dioxide production, acid formation and lactate and pyruvate concentrations of rat liver slices was studied. At the concentrations used, none of the alcohols was found to influence oxygen uptake. Of the alcohols that are not oxidized by liver alcohol dehydrogenase, methanol increased carbon dioxide production, propan-2-ol decreased it and 2-methylpropan-2-ol was without influence. All the alcohols that are oxidized by the enzyme strongly decreased carbon dioxide production. The alcohols that are not oxidized had no marked effect on the lactate/pyruvate concentration ratio, whereas the other alcohols strongly increased the ratio. A highly significant correlation was found between the effects of the alcohol on pyruvate concentration and carbon dioxide production. It is assumed that the shift in the redox potential inhibits the function of the tricarboxylic acid cycle of the liver.

THE EFFECT OF DIPHENYLHYDANTOIN IN VITRO ON THE METABOLISM OF TESTOSTERONE BY RAT LIVER SLICES

1967 ◽  
Vol 56 (3) ◽  
pp. 490-498 ◽  
Author(s):  
Leon J. Sholiton ◽  
Emile E. Werk ◽  
Joseph MacGee
Keyword(s):  
Rat Liver ◽  
Paper Chromatography ◽  
Competitive Inhibition ◽  
Liver Slice ◽  
Female Rat ◽  
Hydroxylase Activity ◽  
Liver Slices ◽  
Specific Activities

ABSTRACT The metabolism of testosterone-4-14C by rat liver slices has been evaluated with and without the presence of diphenylhydantoin (DPH). Radioactive metabolites were identified by paper chromatography and recrystallization to constant specific activities with appropriate standards. With female rat liver slice incubation, under the conditions utilized, androsterone (A) and allo-tetrahydrotestosterone (allo-THT) is increased 4–5 fold by the presence of DPH. In the male, aetiocholanolone (E) and tetrahydrotestosterone (THT) formation is noted with increased conversion to these in the presence of DPH. It is postulated that the DPH effect may be due to competitive inhibition of hepatic microsomal hydroxylase activity while allowing for unabated Δ4-reductase action.

OXYDATION DES ANABOLIKUMS 1-METHYL-ANDROST-1-EN-17β-OL-3-ON MIT WASSERSTOFFTRANSFER AUF ÖSTRON

1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel
Keyword(s):  
Rat Liver ◽  
Anabolic Steroid ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Liver Slices ◽  
Androgen Effects ◽  
Biochemical Difference

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.

scholarly journals THE ESTIMATION OF FATTY ACID SYNTHESIS IN RAT LIVER SLICES

1953 ◽  
Vol 205 (1) ◽  
pp. 401-408
Author(s):  
Grace Medes ◽  
Morris A. Spirtes ◽  
Sidney Weinhouse
Keyword(s):  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Liver Slices

Precision-cut Guinea-pig Liver Slices as a Tool for Studying the Toxicity of Volatile Anaesthetics

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 191-199
Author(s):  
Hanan N. Ghantous ◽  
Jeanne Fernando ◽  
Scott E. Morgan ◽  
A. Jay Gandolfi ◽  
Klaus Brandel
Keyword(s):  
Guinea Pig ◽  
Rank Order ◽  
Normal Liver ◽  
Liver Slice ◽  
Volatile Anaesthetics ◽  
Pig Liver ◽  
Liver Slices ◽  
Guinea Pig Liver ◽  
Krebs Henseleit Buffer

Cultured precision-cut liver slices retain normal liver architecture and physiological biochemical functions. Hartley male guinea-pig liver slices have proven to be a good model for studying the biotransformation and toxicity of halothane. This system was used to evaluate the biotransformation and toxicity of different volatile anaesthetics (halothane, enflurane, isoflurane and sevoflurane), and compare their effects to those of new anaesthetics (desflurane). Liver slices (250–300μm thick) were incubated in sealed roller vials, containing Krebs Henseleit buffer at 37°C under 95% O2:5% CO2 atmosphere. Volatile anaesthetics were delivered by volatilisation after pre-incubation for 1 hour to produce a constant concentration in the medium. Production of the metabolites, trifluroacetic acid and fluoride ion, was measured. Intracellular potassium ion content, protein synthesis and secretion were determined as indicators of viability of the slices. The rank order of biotransformation of anaesthetics by the liver slices was halothane >sevoflurane>isoflurane and enflurane>desflurane. The rank order of hepatotoxicity of these anaesthetics was halothane>isoflurane and enflurane>sevoflurane and desflurane. Halothane is the anaesthetic which is metabolised furthest and has the most toxic effect, while desflurane is the least metabolised anaesthetic and has the least toxicity. This in vitro cultured precision-cut liver slice system appears to be suitable for studying the biotransformation of volatile anaesthetics and correlating its role in the resulting toxicity.

Influence of Slice Thickness and Culture Conditions on the Metabolism of 7-Ethoxycoumarin in Precision-cut Rat Liver Slices

1998 ◽  
Vol 26 (4) ◽  
pp. 541-548
Author(s):  
Roger J. Price ◽  
Anthony B. Renwick ◽  
Paula T. Barton ◽  
J. Brian Houston ◽  
Brian G. Lake
Keyword(s):  
Gas Phase ◽  
Rat Liver ◽  
Xenobiotic Metabolism ◽  
Culture Conditions ◽  
Slice Thickness ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Liver Slices ◽  
Sprague Dawley Rats ◽  
Rat Livers

This study investigated the effects of some experimental variables on the rate of xenobiotic metabolism in precision-cut rat liver slices. Liver slices of 123 ± 8μm (mean ± SEM of six slices), 165 ± 3μm, 238 ± 6μm and 515 ± 14μm thickness were prepared from male Sprague-Dawley rats, and incubated in RPMI 1640 medium in an atmosphere of 95% O2/5% CO2 by using a dynamic organ culture system. Liver slices of all thicknesses metabolised 10μM 7-ethoxycoumarin to total (free and conjugated) 7-hydroxycoumarin in a time-dependent manner. The rate of 7-ethoxycoumarin metabolism was greatest in 165μm thick slices and slowest in 515μm thick slices, being 2.74 ± 0.19pmol/minute/mg slice protein and 0.69 ± 0.07pmol/minute/mg slice protein, respectively. No marked effects on the rate of 7-ethoxycoumarin metabolism in liver slices were observed either by changing the medium to Earle's balanced salt solution (EBSS) or by changing the gas phase to 95% air/5% CO2. Moreover, the perfusion of rat livers with EBSS at 2–4°C, prior to preparation of tissue cores, did not enhance 7-ethoxycoumarin metabolism in rat liver slices. In this study, the optimal slice thickness was 175μm, with higher rates of 7-ethoxycoumarin metabolism being observed than with 250μm thick slices, which are often used for studies of xenobiotic metabolism. Variable results were obtained with slices of around 100–120μm thickness, which may be attributable to the ratio between intact hepatocytes and cells damaged by the slicing procedure in these very thin slices.

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