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Biotin deficiency and liver metabolism in relation to fatty liver and kidney syndrome.

Varying degrees of biotin deficiency were induced by adding freeze-dried, raw egg white to the diet of broiler chicks. Aspects of liver metabolism were studied with reference to fatty liver and kidney syndrome. Mortality was low with 11.8 g egg white/kg diet, or less, but with 17.7 g/kg or more, mortality was very high. High mortality was observed with less than 0.33 microgram biotin/g liver. Associated with low concentrations of liver biotin were substantial increases in liver weight and lipid content in starved birds. The increased liver lipid content was not observed in birds fed ad libitum. The increased liver lipid content in biotin-deficient, starved birds was not reflected in the specific activities of hepatic lipogenic enzymes or hepatic lipogenesis in vivo measured by the incorporation of tritium from 3H-labelled water into liver lipid. Biotin deficiency affected the specific activities of the biotin-requiring enzymes, pyruvate carboxylase and acetyl CoA carboxylase, differently; the latter was unaffected whereas the former decreased concomitantly with liver biotin concentration.

Animals

[Changes in liver metabolism following a standardized skin burn and intraperitoneal injection of a burn toxin isolated from burned mice skin. Studies on rat liver using isolation perfusion].

Parameters of liver metabolism were studied in the isolated perfused rat liver 5 days after a standard skin burn or an i.p. injection of a specific cutaneous burn toxin. Decreased values of the energy quotient ATP/ADP compared with normal controls were found. The absolute content of adenonucleotides was unchanged. The excretion of glucose and urea was also decreased in both groups and glucose synthesis after a lactate load was only slightly stimulated. The results show a direct influence of a burn toxin on hepatic metabolism suggesting a possible disturbance of oxydative phosphorylation.

Adenine Nucleotides

Plasma clearance and liver metabolism of native and asialo-human transcortin in the rat.

Plasma kinetics and liver metabolism of iodinated human corticosteroid-binding protein have been studied in ovariectomized female rats. 125I-labeled human corticosteroid-binding globulin prepared by a modified chloramine T reaction was shown to be physically intact and biologically active. Intravenously injected 125I-labeled human corticosteroid-binding globulin was shown to give a complex clearance pattern from the plasma, with half-lives of 7.5 and 51 min. Estrogen injections had no effect on plasma clearance rate. Direct involvement of liver plasma membrane receptors for asialoglycoproteins in 125I-labeled human corticosteroid-binding globulin metabolism was demonstrated in vivo and in vitro using asialofetuin as a competitive inhibitor. 125I labeled human asialo-corticosteroid-binding globulin was cleared from the plasma with a half-life of less than 1 min, while the simultaneous injection of 5 mg asialofetuin maintained the circulating plasma lebels. Asialofetuin also slowed the clearance of intact 125I-labeled human corticosteroid-binding globulin from the plasma (t1/2 = 90 min). Binding of 125I-labeled human asialo-corticosteroid-binding globulin to rat liver plasma membranes in vitro was inhibited in a dose-dependent manner by asialofetuin, but not by intact human corticosteroid-binding globulin or fetuin. 125I-labeled human corticosteroid-binding globulin did not bind significantly to the membranes. It is concluded that human corticosteroid-binding globulin clearance from rat plasma is rapid and that the carbohydrate moiety of human corticosteroid-binding globulin is involved in its clearance and catabolism by the liver.

Animals

[Liver metabolism of drugs (author's transl)].

Even if all problems of liver metabolism have not yet been clarified, it is nevertheless established that medicaments induces enzymes in the hepatic cells which influence the metabolism of drugs. Because their effect is unspecific, these enzymes can catabolize many drugs with different structures. About 200 substances are known which induce such enzymes. Among them, for example, is phenobarbital. It is therefore used in the treatment of some forms of icterus with freee bilirubin and for Cushing's syndrome. But enzyme induction can also lead to acute intermittent porphyrias and distrubances of the phosphorus-calcium metabolism. Extreme catabolism of a drug can be caused by overinduction of enzymes due to the administration of several incompatible medicaments.

Adult

Mechanisms involved in alpha-adrenergic effects of catecholamines on liver metabolism.

Recent results have indicated that alpha-adrenergic receptors are the major mediators of catecholamine actions on liver metabolism in several species. It is well-established that cAMP and cAMP-dependent protein kinase are not involved in hepatic alpha-adrenergic effects. This review presents evidence that alpha-adrenergic stimulation of glycogenolysis in rat liver involves the mobilization of Ca2+ ions from mitochondria and stimulation of phosphorylase kinase by the resulting increase in cytosolic Ca2+ concentration. Possible mechanisms by which activation of alpha-adrenergic receptors causes release of mitochondrial Ca2+ and affects other cell processes are discussed.

Animals

Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.

Adenosine Triphosphate

Metabolism of delta1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism.

The metabolism of (-)-delta1-tetrahydrocannabinol (delta1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-delta1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC was also present together with small amounts of 6alpha-hydroxy-delta1-THC and 6beta-hydroxy-delta1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6beta-hydroxy-delta1-THC and 6alpha-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of delta1-THC.

Animals

A three-dimensional mouse liver organoid platform for assessing EDCs metabolites simulating liver metabolism.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

Animals

Effects of hyperbaric oxygen and glutathione on mammalian liver metabolism.

The effects of hyperbaric oxygen tensions on oxygen consumption and succinate dehydrogenase (SDH) activity of mouse liver were investigated. Liver homogenates exposed to a PO2 of 3837 mm Hg for 30 min showed a 50.6% reduction in oxygen consumption compared to controls exposed to nitrogen at ambient pressure. The SDH activity was significantly reduced during a 3-h exposure to a PO2 of 3796 mm Hg. The effects of glutathione as a protective agent against oxygen toxicity were also examined. Mouse liver pretreated with reduced glutathione and exposed to hyperbaric oxygen tensions showed higher rates of oxygen consumption than untreated controls. Oxidized and reduced glutathione protected SDH against hyperbaric oxygen inactivation. It is concluded that glutathione can stimulate oxygen consumption and maintain SDH activity after exposure to hyperbaric oxygen by increasing succinate formation through the glutathione-succinate shunt.

Adenosine Triphosphate

[Liver metabolism during massive hemorrhage and subsequent blood transfusion].

Content of lactate, pyruvate as well as activity of hexokinase, phosphorylases, ATPase and transaminases were studied in dog and rat liver tissues under conditions of acute profuse hemorrhage and after its complete compensation by autogenic, isogenic blood and by sodium chloride 0.9% solution. Distinct inhibition of the hexokinase activity in the hemorrhage led to impairment of glucose utilization in liver tissue and to development of hyperglycemia. Alterations in arterial blood pressure correlated with the activity of tissue enzymes. Tissue metabolism was improved after compensation of blood losses by adequate amounts of blood at early period of hemorrhagic shock.

Adenosine Triphosphatases

[Ethanol in parenteral feeding and its effect on liver metabolism].

Investigations of the leucine aminopeptidase (LAP) and the gamma-glutamyl transpeptidase (gamma-GT) as a dimension for a damage of the liver cells under ethanol infusion did not show any damage of the liver parenchyma with a slow infusion velocity and a limited ethanol quantity (25 g daily). Since especially in the postoperative phase a sufficient caloric nutrition improves the therapeutic results, one could make use of the possibility of ethanol supply. This is mainly recommendable for patients who should demand only a small infusion volume or such a one which should not carry a high quantity of sugar (for instance diabetics). The parenteral ethanol application in the postoperative phase is frequently indicated for the immobilisation of alcoholics.

Adult

Effect of epinephrine and alprenolol on ethanol metabolism, liver cell respiration and mitochondrial function.

Chronic administration of epinephrine to adult male rats resulted in a significant increase in the rate of ethanol elimination, when given alone or together with the beta-adrenergic blocker alprenolol. This effect was observed concomitantly with an increased hepatic oxygen utilization and no changes in mitochondrial respiratory functions. Epinephrine given acutely did not modify the rate of ethanol metabolism. Blood glucose levels were enhanced in these conditions, but were unaffected in rats treated with epinephrine plus alprenolol. These results suggest that chronic epinephrine treatment induces an increased oxidative capacity in the liver characterized by enhanced rates of oxygen uptake and ethanol metabolism, which is not related to its beta-adrenergic actions.

Alprenolol

Effect of glucagon and blood transfusion on liver metabolism in hemorrhagic shock.

Treatment with glucagon in addition to blood transfusion was compared with blood transfusion alone after one hour of hemorrhagic shock in the rat. In liver tissue Na+ increased and K+ decreased during haemorrhagic shock. After treatment the initial values were restored equally in both groups within ten minutes. Incubation of liver slices in cold Krebs' solution resulted in a pronounced increase in Na+ and decrease in K+, the values being partially restored to initial levels after subsequent incubation at 37 degrees. Thirty minutes after treatment the liver slices obtained from rats given glucagon showed a more normal ion composition after leaching and rewarming than slices from rats not given glucagon. ATP decreased and glucose and lactate increased in liver tissue during hemorrhagic shock. These variables were partially restored 30 minutes after treatment. No difference between the treatment groups was noted. Animals trreated with glucagon were, however, more efficient in reducing the elevated blood lactate level. The results suggest that the use of glucagon in the treatment of hemorrhagic shock might be of benefit for cellular function in the liver.

Adenosine Triphosphate