Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats.

An acute intraperitoneal injection of ethanol (0.7 or 2.1g/kg body wt.) causes the reversible, dose-dependent accumulation of hepatic triglyceride in rats. By using a pulse of [14C]palmitate injected into a tail vein, it was found that ethanol (2.1g/kg)had no effect on the flux of unesterified fatty acid of serum (4.3mumol/min per 100g body wt.). However, either dose increased the fraction of the total flux going to liver from 0.16 to0.27 as rapidly as could be measured (30s), and it remained elevated until all ethanol had been cleared from the blood. The fraction of the total radioactivity in lipids of liver that was in triglyceride increased linearly for 1 h from 30 to 50% and there was a simultaneous decrease in phospholipid from 60 to 40%. The rate of synthesis of hepatic triglyceride derived directly from unesterified fatty acid of serum was calculated by using the flux rate of unesterified fatty acid in serum, the fractional hepatic uptake of this flux, and the percentage of liver fatty acid esterified to triglyceride. This contribution is related to the total synthetic rate of hepatic triglyceride (rate of accumulation+rate of release) to determine quantitatively how much of the developing fatty liver is attributable to increased uptake of unesterfied fatty acid of serum. At the higher dose of ethanol, about half of the accumulating triglyceride is derived from this source, whereas with the lower dose of ethanol it can account for all of the build-up.     

Effect of ingestion of saline, glucose, and ethanol on mobilization and hepatic incorporation of epididymal pad palmitate-1-14C in rats

The effect of ingestion of saline, glucose, and ethanol (isocaloric with the glucose) on the mobilization of radiopalmitate from epididymal fat prelabeled in vivo and the incorporation of the mobilized label into liver lipids was investigated in rats. The mobilization of radiopalmitate from epididymal fat and the incorporation of the mobilized label into liver triglyceride were most markedly elevated by ingestion of ethanol. Increased mobilization and diversion of epididymal adipose tissue fatty acids to liver lipids of ethanol-treated rats were shown also by the close resemblance of the fatty acids of liver triglyceride to the fatty acids of epididymal fat. The amount of radiopalmitate mobilized by the saline-treated rats, comprising approximately a third of that mobilized by the ethanol-treated animals, was larger than the amount mobilized by the rats treated with glucose; most of it was oxidized rather than incorporated into the liver fats. In glucose-treated rats a larger fraction of radiopalmitate mobilized from one prelabeled epididymal pad was diverted to and incorporated into the lipids of the contralateral pad of the same animal. The specific activity of hepatic triglyceride of ethanol- and saline-treated rats was similar and significantly higher than that of animals treated with glucose. These data indicate that the ethanol-induced fatty liver can be attributed to an increased mobilization and incorporation of adipose tissue fatty acids into liver lipid and to an altered hepatic metabolism of fatty acids and triglyceride.     

Effect of propranolol and cycloheximide on the ethanol-induced increase in liver tryptophan oxygenase activity in starved rats

Increased supply of trytophan to the liver, resulting from the lipolytic action of ethanol, is suggested to be responsible for the increased activity of liver tryptophan oxygenase after ingestion of a single large dose of ethanol. This hypothesis was tested using an antilipolytic drug, propranolol, prior to ethanol treatment. It was found that, while propronolol did inhibit the ethanol-induced increase in blood unesterified fatty acids and free tryptophan concentrations it did not prevent the activation of tryptophan oxygenase by ethanol. In another experiment, where cycloheximide was used to block protein synthesis, it was found that increased protein synthesis rather than decreased protein degradation is probably responsible for the accumulation of liver tryptophan oxygenase after ethanol ingestion.     

Effect of propranolol and cycloheximide on the ethanol-induced increase in liver tryptophan oxygenase activity in starved rats

Increased supply of tryptophan to the liver, resulting from the lipolytic action of ethanol, is suggested to be responsible for the increased activity of liver tryptophan oxygenase after ingestion of a single large dose of ethanol. This hypothesis was tested using an antilipolytic drug, propranolol, prior to ethanol treatment. It was found that, while propranolol did inhibit the ethanol-induced increase in blood unesterified fatty acids and free tryptophan concentrations, it did not prevent the activation of tryptophan oxygenase by ethanol. In another experiment, where cycloheximide was used to block protein synthesis, it was found that increased protein synthesis rather than decreased protein degradation is probably responsible for the accumulation of liver tryptophan oxygenase after ethanol ingestion.     

The enterohepatic recycling of bile choline in sheep

1. Measurement of unesterified choline in blood samples taken from five conscious multi-cannulated sheep indicated a significant production of unesterified choline by the alimentary tract, as judged by the portal venous minus arterial difference and significant uptake by the liver, as judged from the portal venous minus hepatic venous and arterial minus hepatic venous differences. 2. A mean liver blood flow rate of 1.68 +/- 0.22 1/min for the five sheep was determined by bromosulphophthalein clearance and, combined with the differences in unesterified choline across organs, gave a production rate of free choline of 9.1 mmol/day by the alimentary tract and an uptake by the liver of 13.2 mmol/day. 3. Infusion of [methyl-3H]choline chloride into the portal vein of a sheep over 1 hr and subsequent isolation of the bile for several days showed over 70% cumulative recovery of the radioactivity in the choline moiety of bile phosphatidylcholine over a 120 hr period. 4. Subsequent infusion 17 days later of bile lipid [3H]choline via a duodenal fistula also gave approx. 70% cumulative recovery of radioactivity in the choline moiety of newly secreted bile phosphatidylcholine in 120 hr. 5. These results show a very extensive enterohepatic recirculation of bile choline in the sheep, which is in contrast to the situation in monogastric animals.     

Hepatic processing and biliary secretion of the cholesteryl esters from beta very-low-density lipoproteins in the rat

beta-Migrating very-low-density lipoproteins (beta-VLDL) are cholesteryl-ester-enriched lipoproteins which accumulate in the serum of cholesterol-fed animals or patients with type III hyperlipoproteinemia. In the rat, beta-VLDL are rapidly cleared by the liver and parenchymal liver cells form the major site for uptake. In this investigation, beta-VLDL were labeled with [3H]cholesteryl esters and the hepatic intracellular transport of these esters was followed. 2 min after injection, the major part of the [3H]cholesteryl esters is already associated with the liver and a significant proportion is recovered in endosomes. Up to 25 min after injection, an increase in radioactivity in the lysosomal compartment is noticed. This radioactivity initially represents cholesteryl esters, while from 25 min onward, radioactivity is mainly present in unesterified cholesterol. Between 45 min and 90 min after beta-VLDL injection, specific transfer of unesterified [3H]cholesterol to the endoplasmic reticulum is observed, while by 3 h the majority is located in this fraction. The appearance of radioactivity in the bile was rather slow as compared to the rapid initial uptake and processing, and up to 5 h after injection only 10% of the injected dose had reached the bile (mainly as bile acids). 72 h after injection, the amount of the injected radioactivity recovered in the bile had increased to 50%. Chloroquine treatment of the rats inhibited the hydrolysis of the cholesteryl esters and the appearance of radioactivity in the bile was retarded. It is concluded that beta-VLDL are rapidly processed by parenchymal liver cells and that the cholesteryl esters from beta-VLDL are hydrolyzed in the lysosomal compartment. Unesterified cholesterol remains associated with the endoplasmic reticulum for a prolonged time, although ultimately the majority will be secreted into the bile as bile acids. The effective operation of this pathway will prevent extrahepatic accumulation of cholesteryl esters from beta-VLDL, while the prolonged residence time of unesterified cholesterol in the endoplasmic reticulum might be important for regulation of low-density lipoprotein (LDL) receptors in liver and thus for LDL levels in the blood.     

Decreased expression of peroxiredoxin 6 in a mouse model of ethanol consumption

Alcoholic liver disease is multifactorial and oxidative stress is believed to play an intimate role in the initiation and progression of this pathology. The goals of this study were to investigate the effect of chronic ethanol treatment on inducing hepatic oxidative stress and peroxiredoxin 6 expression. After 9 weeks of treatment with an ethanol-containing diet, significant increases in serum ALT activity, liver to body weight ratio, liver triglycerides, CYP2E1 protein expression, and CYP2E1 activity were observed. Chronic ethanol feeding resulted in oxidative stress as evidenced by decreases in hepatic glutathione content and increased deposition of 4-hydroxynonenal and 4-oxononenal protein adducts. In addition, novel findings of decreased PRX6 protein and mRNA and increased levels of carbonylated PRX6 protein were observed in the ethanol-treated animals compared to the pair-fed controls. Lastly, NF-kappaB activity was found to be significantly increased in the ethanol-treated animals. Concurrent with the increase in NF-kappaB activity, decreases in both MEK1/2 and ERK1/2 phosphorylation were also observed in the ethanol-treated animals compared to the pair-fed controls. Together, these data demonstrate that chronic ethanol treatment results in oxidative stress, implicating NF-kappaB activation as an integral mechanism in the negative regulation of PRX6 gene expression in the mouse liver.     

Metabolism of hepatic and plasma triglycerides in rabbits given ethanol or ethionine

The formation and transport of hepatic triglyceride fatty acids (TGFA) were studied after intravenous administration of palmitate-1-(14)C or palmitate-9,10-(3)H in rabbits pretreated with ethanol or ethionine. Administration of ethanol produced significant hypertriglyceridemia without consistent accumulation of hepatic fat. The isotopic studies suggest that plasma free fatty acids were the major precursors of TGFA in d < 1.006 lipoproteins and that fatty acids synthesized in the liver were not the source of the hypertriglyceridemia in the ethanol-treated animals. Administration of ethionine resulted in an increased concentration of TGFA in the liver, a decreased level of TGFA in d < 1.006 lipoproteins and a very low specific activity in this plasma fraction. These findings suggest that the development of fatty liver after administration of ethionine is in part accompanied by impaired release of TGFA from the liver.     

Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.

Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.     

Unsaturated Fatty Acids Esterified in 2-Acyl-1-Lysophosphatidylcholine Bound to Albumin Are More Efficiently Taken up by the Young Rat Brain than the Unesterified Form

The aim of the present study was to investigate whether unsaturated 2-acyl-lysophosphatidylcholine bound to plasma albumin is a relevant delivery form of unsaturated fatty acids to the developing brain. Twenty-day-old rats were perfused for 30 s with labeled palmitic, oleic, linoleic, and arachidonic acids in either their unesterified form or esterified in 2-acyl-lysophosphatidylcholine labeled on the choline and fatty acid moieties. Both forms were bound to albumin. Incorporation in brain lipid classes was followed within 1 h. The brain uptake of the unesterified fatty acids reached a plateau at 5-15 min and was maximal for arachidonic acid (0.45% of the perfused dose). The brain uptake of palmitoyl-lysophosphatidylcholine was similar to that of palmitic acid, whereas that of other lysophosphatidylcholines increased with the degree of unsaturation (rate and maximal uptake) and was six- to 10-fold higher than that of the corresponding unesterified fatty acid. 2-Acyl-lysophosphatidylcholines were taken up without prior hydrolysis and reacylated into doubly labeled phosphatidylcholine, which was the most labeled lipid class, whereas lipid distribution of the unesterified fatty acid was more diversified. Partial hydrolysis of 2-acyl-lysophosphatidylcholine occurred in the brain tissue, and redistribution of the fatty acyl moiety into other phospholipid classes was also observed and was the highest for arachidonic acid. In this case, the percentage of esterification of this fatty acid in phosphatidylinositol (expressed as a percentage of the total lipid fraction) was relatively lower than that observed when the unesterified form was used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nuclear activation and translocation of mitogen-activated protein kinases modulated by ethanol in embryonic liver cells

Activation and nuclear translocation of mitogen activated protein (MAP) kinases in ethanol-treated embryonic liver cells (BNLCL2) was investigated. The relative amount of MAPK proteins, MAP kinase activity and MAPK/LDH (lactate dehydrogenase) ratios were determined in nuclear and cytosolic fractions before and after serum stimulation. In ethanol-treated cells, serum-stimulated MAPK activation was potentiated in both cytosolic and nuclear fractions. Levels of both the p42 and p44 MAPK proteins increased in nuclear fractions from cells treated with ethanol alone for 24 h. Serum-stimulated nuclear translocation of both p42 and p44 MAPK was potentiated in ethanol-treated cells. Nuclear fractions from ethanol-treated cells had a modest increase in MAP kinase activity concurrent with the increased MAPK protein levels. The ratio of MAPK/LDH increased in nuclear fractions with increasing concentrations of ethanol and after serum stimulation. This further confirmed the nuclear translocation of MAPK and also demonstrated that it is not a non-specific effect of ethanol. These results demonstrate, for the first time, that in BNLCL2 liver cells ethanol treatment has dual effects. First, ethanol triggered nuclear translocation of MAPK without causing its activation. Second, it potentiated serum-stimulated activation and translocation of MAPK in the nucleus. These findings provide a novel mechanism through which ethanol may affect cellular and nuclear processes in liver cells.     

Chronic ethanol consumption induces histopathological changes and increases nitric oxide generation in the rat liver

In the present work we evaluated the effect of ethanol consumption in histopathological liver changes and several biochemical biomarkers employed in the detection of hepatic dysfunction. Male Wistar rats were treated with ethanol 20% (vol/vol) for 6 weeks. Histopathological investigation of livers from ethanol-treated animals revealed steatosis. Indices of hepatic function (transaminases) and mitochondrial respiration were not altered in ethanol-treated rats. Chronic ethanol consumption did not alter malondialdehyde (MDA) levels in the liver. Ethanol consumption induced a significant increase on hepatic nitrite and nitrate levels. Treatment with ethanol increased both mRNA expression and immunostaining of iNOS, but not eNOS. Finally, ethanol consumption did not alter hepatic levels of metalloproteinase (MMP)-2 and MMP-9. We conclude that alterations on biochemical biomarkers (nitrite and nitrate levels) and histopathology occurred in ethanol-treated rats, supporting the practice of including both types of evaluation in toxicity studies to detect potential ethanol-related hepatic effects. In our model of ethanol consumption, histopathological liver changes were accompanied by elevation in nitrite and nitrate levels indicating increased nitric oxide (NO) generation. Since iNOS-derived NO contributes to hepatic injury, the increased levels of NO described in our study might contribute to a progressive hepatic damage. Therefore, increases in NO generation may be an early indicator of ethanol-induced liver damage.     

Effects of ethynyloestradiol on the metabolism of [1-14C]-oleate by perfused livers and hepatocytes from female rats

Normal female rats were given 15mug of ethynyloestradiol/kg body wt. for 14 days and were killed on day 15 after starvation for 12-14h. The livers were isolated and were perfused with a medium containing washed bovine erythrocytes, bovine serum albumin, glucose and [1-(14)C]oleic acid; 414mumol of oleate were infused/h during a 3h experimental period. The output of bile and the flow of perfusate/g of liver were decreased in livers from animals pretreated with ethynyloestradiol, whereas the liver weight was increased slightly. The rates of uptake and of utilization of [1-(14)C]oleate were measured when the concentration of unesterified fatty acid in the perfusate plasma was constant. The uptake of unesterified fatty acid was unaffected by pretreatment of the animal with oestrogen; however, the rate of incorporation of [1-(14)C]oleate into hepatic and perfusate triacylglycerol was stimulated, whereas the rate of conversion into ketone bodies was impaired by treatment of the rat with ethynyloestradiol. Pretreatment of the rat with ethynyloestradiol increased the output of very-low-density lipoprotein triacylglycerol, cholesterol, phospholipid and protein. The production of (14)CO(2) and the incorporation of radioactivity into phospholipid, cholesteryl ester and diacylglycerol was unaffected by treatment with the steroid. The net output of glucose by livers from oestrogen-treated rats was impaired despite the apparent increased quantities of glycogen in the liver. The overall effect of pretreatment with oestrogen on hepatic metabolism of fatty acids is the channeling of [1-(14)C]oleate into synthesis and increased output of triacylglycerol as a moiety of the very-low-density lipoprotein, whereas ketogenesis is decreased. The effect of ethynyloestradiol on the liver is apparently independent of the nutritional state of the animal from which the liver was obtained. It is pertinent that hepatocytes prepared from livers of fed rats that had been treated with ethynyloestradiol produced fewer ketone bodies and secreted more triacylglycerol than did hepatocytes prepared from control animals. In these respects, the effects of the steroid were similar in livers from fed or starved (12-14h) rats. Oestrogens may possibly inhibit hepatic oxidation of fatty acid, making more fatty acid available for the synthesis of triacylglycerol, or may stimulate the biosynthesis of triacylglycerol, or may be active on both metabolic pathways.     

Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells

Well-differentiated Reuber H35 rat hepatoma cells in culture maintain a variety of biochemical functions characteristic of hepatocytes [Deschatrette, J., and M. C. Weiss. 1974. Biochimie. 56: 1603-1611]. To demonstrate the suitability of this system as a model for exploring mechanisms of ethanol hepatotoxicity, the following were investigated: 1) ethanol metabolism in whole cells and cell extracts and 2) effects of ethanol exposure on cellular lipid content. Cultures of H35 cells exposed to 10 mm ethanol metabolized the ethanol at rates similar to those reported in rat liver. Under these conditions, soluble alcohol dehydrogenase activity accounted for greater than 87% of total ethanol metabolism. H35 cells exposed to 240 mm ethanol for 3 days contained four times more triacylglycerol and cholesteryl ester than control cells. Total phospholipid and unesterified cholesterol levels were unaffected by ethanol. Neutral lipid content of Chinese hamster ovary cells was unchanged after ethanol exposure. The increased triacylglycerol content of ethanol-treated H35 cells appeared to result from an accelerated rate of conversion of long chain fatty acids into triacylglycerol. Several lines of evidence indicated that alcohol dehydrogenase-mediated ethanol oxidation was critical in promoting increased triacylglycerol content of cultured cells. Since 240 mm ethanol blocked cellular proliferation, long term effects of ethanol were studied at a level of 10 mm, which allowed a nearly normal growth rate. After 7 weeks of continuous exposure, 10 mm ethanol-treated H35 cells contained five times more triacylglycerol than paired controls. The well-differentiated H35 cell appears to be an excellent in vitro model system for studying both short-term and long-term effects of ethanol on liver cells.-Polokoff, M. A., M. Iwahashi, and F. R. Simon. Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells.     

Quantitative proton nuclear magnetic resonance of plasma for screening hepatic metabolism during ethanol infusion in cats

The effects of increasing blood ethanol levels on hepatic metabolism were studied in anesthetized cats whose prior fluid intake contained ethanol for 24 days. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of blood volume. For ethanol, Vmax was 106 +/- 15 mumol.min-1.100 g-1 liver and Km was 164 +/- 31 microM. A previous study showed that there were no changes in O2 uptake by the liver, suggesting other oxidative processes were suppressed during ethanol metabolism. In this study, proton nuclear magnetic resonance spectroscopy was used to simultaneously screen several plasma metabolites to elucidate other metabolic processes that may be perturbed in the liver during ethanol infusion. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose above 0.5 Vmax. Thus, lactate oxidation is one process that can be suppressed to allow ethanol oxidation without additional O2 uptake by the liver. In addition, no release of acetate from the liver occurred during ethanol metabolism in these experiments. This surprising finding suggests ethanol metabolism may, under some conditions or in some species, result in fatty acid synthesis rather than acetate release. Eight other major metabolites remained unchanged during ethanol infusion.     

Uptake and output of various forms of choline by organs of the conscious chronically catheterized sheep.

The net uptake and output of plasma unesterified choline, glycerophosphocholine, phosphocholine and lipid choline by organs of the conscious chronically catheterized sheep were measured. There was significant production of plasma unesterified choline by the upper- and lower-body regions and the alimentary tract and uptake by the liver, lungs and kidneys. The upper- and lower-body regions drained by the venae cavae provided the bulk (about 82%) of the total body venous return of plasma unesterified choline. Production of plasma unesterified choline by the alimentary tract was approximately balanced by the plasma unesterified choline taken up by the liver, and was almost equal to the amount of choline secreted in the bile. There was a considerable amount of glycerophosphocholine in the liver and there was production of plasma glycerophosphocholine by the liver and uptake by the lungs and kidneys. Glycerophosphocholine was higher in the plasma of sheep than in that of rats. Plasma phosphocholine was produced by the alimentary tract and kidneys. There was production of plasma lipid choline by the upper- and lower-body regions drained by the venae cavae. The results suggest that the sheep synthesizes substantial amounts of choline in ectrahepatic tissues and has the capacity for extensive retention and recycling of bile choline. These observations, coupled with a slow turnover of the endogenous choline body pool, explain the low requirement of sheep for dietary choline in contrast with non-ruminant species.     

The biliary excretion of enterokinase in rats. Studies in normal, chronic ethanol-maintained and cirrhotic rats.

The excretion of catalytically active human or pig enterokinase in hepatic bile after intravenous administration to normal rats or rats that had been maintained on 20% (v/v) ethanol for 1 year showed similar kinetics to that described for other serum-derived bile proteins. The half-life in serum was 2.5 min or less, and most of the enzyme was excreted within 45 min of administration. This was maintained when up to six successive doses were given at 90 min intervals. The mean amount excreted per dose was independent of the dose number and varied from 0.8% to 2.1% in the normal animals and 1.2% to 2.0% in the chronic ethanol-maintained animals. When three doses of enzyme were given at 30 min intervals, the total amount of active enterokinase recovered in bile was dose-dependent and was consistently higher in the rats drinking 20% (v/v) ethanol. The serum half-life of enterokinase in rats made cirrhotic by inhalation of carbon tetrachloride vapour was extended to 6 min or more. The amount of active enzyme recovered in bile was at least 50% less than in weight-matched normal rats, and excretion was not complete 2h after intravenous administration. The possible significance of these findings in liver and pancreatic disease is discussed.     

Derecruitment in cat liver: extension of undistributed parallel tube model to effects of low hepatic blood flow on ethanol uptake

Previous studies showed two deviations from the predictions of the undistributed parallel tube model for hepatic uptake of substrates: a small deviation at high flows and a large deviation at low flows. We have examined whether these deviations could be described by a single correction factor. In cats anesthetized with pentobarbital, a hepatic venous long-circuit technique with an extracorporeal reservoir was used to vary portal flow and hepatic venous pressure, and allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic uptake of ethanol was measured over a wide range of blood flows and when intrahepatic pressure was increased at low flows. This uptake could be described by the parallel tube model with a correction for hepatic blood flow: Uptake = Vmax max.(1 - e-kF).c/(Km + c). In 22 cats, Vmax max = 90 +/- 5 mumols/(min.100 g liver), k = 0.021 +/- 0.0015 when flow (F) was in millilitres per minute per 100 g liver, and Km = 150 +/- 20 microM when c is the log mean sinusoidal concentration. (1 - e-kF) represents the proportion of sinusoids perfused and metabolically active. A dynamic interpretation of this proportion is related to intermittency (derecruitment) of sinusoidal flow. Half the sinusoids were perfused at a flow of 33 mL/(min.100 g liver) and the liver was essentially completely perfused (greater than 95%) at the normal flow of 150 mL/(min.100 g liver). Derecruitment was not changed by raising hepatic venous pressure, and it was not related to hepatic venous resistance.     

Serum and lymph lipids in rabbits with carbon tetrachloride-induced cirrhosis of the liver

Lymph flow and the composition of lymph lipids from the hepatic and thoracic ducts of rabbits with cirrhosis of the liver (induced by 46-51 intramuscular injections of a mixture of carbon tetrachloride and olive oil at 4-day intervals) have been compared with those of control animals injected with olive oil only. In cirrhotic animals, the concentration of lymph lipids was not greatly altered, but lymph flow, and consequently the hourly transport of lipids by lymph were greatly increased; the increase in transport of cholesteryl esters, free cholesterol, and phospholipids by way of the thoracic and hepatic duct lymph was particularly striking. The concentration of these lipid fractions in serum from the cirrhotic rabbits was also increased. The differences normally observed between lipid fatty acid compositions of serum and lymph disappeared in cirrhotic animals; this is interpreted as due to increased hepatic permeability to lipoproteins.     

Short-term Effects of Ethanol Intoxication on Ascorbic Acid and Lipid Metabolism and on Drug-metabolizing Enzymes in Liver of Rats

The effects of one-time ethanol intoxication on ascorbic acid and lipid metabolism and on drug-metabolizing enzymes in liver of rats were investigated. Male Donryu rats that had been fed semi-purified feed were given 5 g/kg ethanol solution (25%, w/v) via a stomach tube and killed 16 h after intubation. The amount of ascorbic acid excreted in the urine after ethanol administration increased, but renal and adrenal concentrations of ascorbic acid decreased. The serum levels of total cholesterol, high-density-lipoprotein cholesterol, triglycerides, phospholipids, and non-esterified fatty acids were elevated in rats given ethanol, but hepatic level of total lipids, cholesterol, triglycerides, phospholipids were not. The hepatic concentrations of cytochrome P-450 and cytochrome b₅ did not increase, but this large dose of ethanol increased the activities of aminopyrine N-demethylase and cytochrome c reductase.

These results indicated that the single dose of ethanol affected the ascorbic acid and lipid metabolism of rats, and induced drug-metabolizing enzymes in their liver.