scholarly journals Factors that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration

1970 ◽  
Vol 118 (2) ◽  
pp. 275-281 ◽  
Author(s):  
L. Videla ◽  
Y. Israel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Succinate Dehydrogenase ◽  
Rat Liver ◽  
Chronic Administration ◽  
Ethanol Metabolism ◽  
Gas Mixture ◽  
Ethanol Treatment ◽  
Liver Slices ◽  
Low Concentrations ◽  
Alcohol Dehydrogenase Activity

1. 2,4-Dinitrophenol (0.1mm) increases by 100–160% the rate of ethanol metabolism by rat liver slices incubated in a medium saturated with a gas mixture containing O2+CO2+N2 (18:5:77). Similar effects are produced by relatively low concentrations of arsenate (10mm). At higher concentrations (37.5 and 50mm) arsenate inhibits the rate of ethanol metabolism. 2. When liver slices are incubated under an atmosphere containing O2+CO2 (95:5) the metabolism of ethanol increases by about 100% over that obtained with O2+CO2+N2 (18:5:77). However, under these conditions the activating effect of dinitrophenol is no longer observed. 3. Chronic administration of ethanol to rats for 3–4 weeks, in doses from 3 to 8g/kg per day, increases by 70–90% the ability of the liver to metabolize ethanol. In the liver slices of these rats, although an O2+CO2+N2 (18:5:77) mixture was used, dinitrophenol does not further increase the metabolism of ethanol. If the chronic administration of ethanol is discontinued for two weeks, the rate of ethanol metabolism is lowered to control values and the activating effect of dinitrophenol is recovered. 4. No change in alcohol dehydrogenase activity was found in the liver of the rats in which the metabolism of ethanol had been increased as a result of the chronic ethanol treatment; a 40% increase in the activity of succinate dehydrogenase was observed.

scholarly journals Modulation of alcohol dehydrogenase and ethanol metabolism by sex hormones in the spontaneously hypertensive rat. Effect of chronic ethanol administration

1980 ◽  
Vol 186 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Gloria Rachamin ◽  
J. Alain Macdonald ◽  
Samina Wahid ◽  
Jeremy J. Clapp ◽  
Jatinder M. Khanna ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Metabolic Rate ◽  
Dehydrogenase Activity ◽  
Chronic Administration ◽  
Ethanol Metabolism ◽  
Ethanol Administration ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Alcohol Dehydrogenase Activity

In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17β to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.

Regulation of oxygen consumption in rat liver slices

1964 ◽  
Vol 206 (5) ◽  
pp. 1091-1094 ◽  
Author(s):  
Herbert L. Kayne ◽  
Natsu Taylor ◽  
Norman R. Alpert
Keyword(s):  
Oxygen Consumption ◽  
Rat Liver ◽  
Adenine Nucleotides ◽  
Pyridine Nucleotide ◽  
Liver Slices ◽  
Low Concentrations ◽  
The Relationship ◽  
Fasted Rats

Oxygen consumption, ATP, ADP, and reduced and oxidized pyridine nucleotide were measured in liver slices which were taken from fed, fasted, and refed rats and subjected to varying durations of anoxia. Oxygen consumption was low in slices from fasted rats and was increased after anoxia in all three groups of rats. Liver slices from fasted rats were also characterized by low concentrations of adenine nucleotides and oxidized pyridine nucleotide. These decreased during anoxia in all groups. Reduced pyridine nucleotide was low in fasted rats, intermediate in fed, and high in refed rats. There was an increase in concentration after 5 min of anoxia. The relationship among these variables is discussed in regard to the concept of nucleotide control of oxygen consumption.

Ethanol metabolism by the rat heart and alcohol dehydrogenase activity

1976 ◽  
Vol 54 (6) ◽  
pp. 539-545 ◽  
Author(s):  
G. W. Forsyth ◽  
H. T. Nagasawa ◽  
C. S. Alexander
Keyword(s):  
Alcohol Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Rat Heart ◽  
Specific Activity ◽  
Ph Dependence ◽  
Ethanol Metabolism ◽  
Minor Role ◽  
Alcohol Dehydrogenase Activity ◽  
A Minor

Rat hearts perfused with oxygenated buffer containing [1-14C]ethanol metabolized small amounts of the ethanol to carbon dioxide. Very sensitive techniques are required to separate the resulting 14CO2 from the ethanol. This metabolism is not inhibited by levels of pyrazole which markedly inhibit NAD dependent liver alcohol dehydrogenase (EC 1.1.1.1). In vitro studies suggest that NADP functions as a cofactor for the rat heart alcohol dehydrogenase activity of crude heart homogenates. The kinetic parameters, the specific activity, and the pH dependence of the enzyme activity measured in these experiments suggest that it may have a minor role in ethanol metabolism by the rat.

scholarly journals Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis

2010 ◽  
Vol 299 (3) ◽  
pp. G661-G668 ◽  
Author(s):  
Courtney S. Schaffert ◽  
Michael J. Duryee ◽  
Robert G. Bennett ◽  
Amy L. DeVeney ◽  
Dean J. Tuma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cytokine Production ◽  
Smooth Muscle Actin ◽  
Thiobarbituric Acid ◽  
Ethanol Metabolism ◽  
Thiobarbituric Acid Reactive Substance ◽  
Ethanol Treatment ◽  
Liver Slices

Ethanol metabolism in the liver induces oxidative stress and altered cytokine production preceding myofibroblast activation and fibrogenic responses. The purpose of this study was to determine how ethanol affects the fibrogenic response in precision-cut liver slices (PCLS). PCLS were obtained from chow-fed male Wistar rats (200–300 g) and were cultured up to 96 h in medium, 25 mM ethanol, or 25 mM ethanol and 0.5 mM 4-methylpyrazole (4-MP), an inhibitor of ethanol metabolism. Slices from every time point (24, 48, 72, and 96 h) were examined for glutathione (GSH) levels, lipid peroxidation [thiobarbituric acid-reactive substance (TBARS) assay], cytokine production (ELISA and RT-PCR), and myofibroblast activation [immunoblotting and immunohistochemistry for smooth muscle actin (SMA) and collagen]. Treatment of PCLS with 25 mM ethanol induced significant oxidative stress within 24 h, including depletion of cellular GSH and increased lipid peroxidation compared with controls ( P < 0.05). Ethanol treatment also elicited a significant and sustained increase in interleukin-6 (IL-6) production ( P < 0.05). Importantly, ethanol treatment accelerates a fibrogenic response after 48 h, represented by significant increases in SMA and collagen 1α(I) production ( P < 0.05). These ethanol-induced effects were prevented by the addition of 4-MP. Ethanol metabolism induces oxidative stress (GSH depletion and increased lipid peroxidation) and sustained IL-6 expression in rat PCLS. These phenomena precede and coincide with myofibroblast activation, which occurs within 48 h of treatment. These results indicate the PCLS can be used as in vitro model for studying multicellular interactions during the early stages of ethanol-induced liver injury and fibrogenesis.

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