Immunohistochemical localization of glutamine synthetase in human liver

Glutamine synthetase (GS) of human liver was recognized with a polyclonal antibody to pig brain GS, but failed to stain with an antibody against rat liver GS. Using the latter antibody GS of human liver was shown to be localized within small rings of 1 to 3 hepatocytes surrounding the terminal hepatic venules. This pattern was analogous to that seen in rat and mouse liver.     

Immunohistochemical localization of glutamine synthetase in human liver

Glutamine synthetase (GS) of human liver was recognized with a polyclonal antibody to pig brain GS, but failed to stain with an antibody against rat liver GS. Using the latter antibody GS of human liver was shown to be localized within small rings of 1 to 3 hepatocytes surrounding the terminal hepatic venules. This pattern was analogous to that seen in rat and mouse liver.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems.

The covalent binding of tritiated benzo(a)pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP and DNA) and the biologically most relevant system (in vivo).     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

Summary 24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Comparison in genetically obese and normal rats in the secretion of lipids synthesized from labeled lauric and oleic acids and glycerol in isolated perfused liver]

(1) Isolated livers of previously fasted fafa and Wistar Rats are perfused with labelled oleic acid and glycerol. Two pools of synthesized lipids are studied: --a pool of liver lipids: labelled TG 16:0, 16:0, 18:1, 16:0, 18:1, 18:1 and 18:1, 18:1, 18:1 are synthesized more by the fafa than by the Wistar Rat liver, The TG 16:0, 18:1, 18:2 appears in the liver of the 2 rat strains. After a 30 min. perfusion, the PL are synthesized less by the fafa than by Wistar Rat liver; --a pool of lipids released in the circulation. The labelled tG 16:0, 18:1, 18:2, are increased in the perfusate of fafa rat. The labelled TG 18:1, 18:1, 18:2 and 18:1, 18:2, 18:2 are in the same amount. (2) The liver synthesis of TG 12:0, 12:0, 12:0 is demonstrated in the fafa Rat by a lauric acid perfusion. This TG is not present in circulation, when a Wistar Rat liver synthesizes and releases with this TG, TG containing 1 or 2 molecules of lauric acid.     

Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy

For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH₂-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.Received 15 September 2003; received after revision 26 October 2003; accepted 19 November 2003     

Expression of the genes of interferons and other cytokines in normal and diseased tissues of man

Specific interferon genes are transcribed at low levels in the spleen, liver, and peripheral blood leukocytes of normal individuals in the apparent absence of virus infection while other interferon genes remain unexpressed in the same tissues. In contrast, the genes of cytokines such as IL-1, IL-6 and TNF are expressed at relatively high levels in the organs of normal individuals. The level of expression of the IL-1, IL-6 and TNF genes is markedly reduced in the livers of patients with autoimmune liver disease compared to the level of expression in the liver of normal individuals, whereas the expression of interferon genes is similar in both normal and diseased liver, suggesting that a defect in the expression of specific cytokines is associated with severe liver disease.     

Endocrine control of lysosomal alterations in rat liver during the perinatal period

Summary Within hours of birth, some physical properties of liver lysosomes are modified. These alterations, which may be related to the autophagic vacuoles formation known to occur during this period, were inhibited by insulin administration. Glucagon, a potent inducer of autophagy in adult rat liver, did not anticipate this process in fetal liver. Our results suggest that the decrease of plasma insulin immediately after birth is a important factor in the development of hepatic autophagy.     

Pseudocholinesterase in obesity: Hypercaloric diet induced changes in experimental obese mice

Summary Pseudocholinesterase activity is significantly higher in liver and serum, but lower in adipose tissue of genetically obese, diabetic and gold thioglucose treated mice. Similar enzyme changes were also observed in lean mice on a high carbohydrate diet. A marked reduction (40%) in PChE activity occurred in the liver of genetically diabetic mice when starved for 24 h. These observations suggest that pseudocholinesterase induction in the liver and repression in the adipose tissue is affected by excessive calorie intake in obesity. This provides a model to study the biological function of PChE in health and disease.Acknowledgments. We thank Dr Charles A. Janeway Child Health Centre and Faculty of Medicine, Memorial University of Newfoundland for financial support.     

Der Einfluss der experimentellen Leberschädigung auf Gesamtfett und ungesättigte Fettsäuren in Serum und Leber

Summary In experiments on rats with CCl₄-induced liver damage the total lipids and the di- to tetra-enoic fatty acids were estimated. The acute experiment of 72 h duration showed a strong augmentation of total lipids and a transitory diminution of arachidonic acid in serum and liver which two months after the intoxication still persisted together with a marked rise in linolenic acid. The parallelism of changes of saturation of the fatty acids in serum and liver being statistically significant indicates that the process of desaturation is most probably localized in the liver itself.     

Liver vitamin A stores in chronic alcoholism in rats: effect of propylthiouracil treatment

Administration of alcohol to rats through drinking water for 8 weeks produced a significant decrease in the liver vitamin A stores without causing any change in the plasma vitamin A levels. Treatment of the alcoholic rats with propylthiouracil for 2 weeks restored the liver vitamin A reserves to control levels.     

Evidence for synergism in steroid hormone-receptor association.

A number of glucocorticoids stimulated oestradiol binding to liver cytosol receptor; oestradiol activated glucocorticoid receptor association at a time when it reversed triamcinolone mediated increase in liver glycogen synthesis.     

Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats

The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production. Received 25 October 2000; received after revision 14 December 2000; accepted 11 January 2001     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Liver vitamin A stores in chronic alcoholism in rats: Effect of propylthiouracil treatment

Summary Administration of alcohol to rats through drinking water for 8 weeks produced a significant decrease in the liver vitamin A stores without causing any change in the plasma vitamin A levels. Treatment of the alcoholic rats with propylthiouracil for 2 weeks restored the liver vitamin A reserves to control levels.     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Summary Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Endocrine control of lysosomal alterations in rat liver during the perinatal period

Within hours of birth, some physical properties of liver lysosomes are modified. These alterations, which may be related to the autophagic vacuoles formation known to occur during this period, were inhibited by insulin administration. Glucagon, a potent inducer of autophagy in adult rat liver, did not anticipate this process in fetal liver. Our results suggest that the decrease of plasma insulin immediately after birth is an important factor in the development of hepatic autophagy.     

The role of maternal parathyroids and vitamin D3 metabolites in fetal growth and the deposition of glycogen reserves in the maternal and fetal liver in rats]

Thyro-parathyroidectomy of pregnant Rats at 12.5 days of gestation decreased maternal liver glycogen on 21.5 days of gestation and fetal weight as well as fetal liver glycogen stores. The graft of one parathyroid gland or the injection of 1 alpha-hydroxycholecalciferol in these thyro-parathyroidectomized mothers increased their liver glycogen stores at 21.5 days of gestation. These treatments also markedly increased both fetal weight and fetal liver glycogen stores. It was concluded that maternal 1,25-dihydorxycholecalciferol, which is synthesized under the control of parathyroid hormone secretion, controls fetal growth and liver glycogen stores. The mechanism of these effects (direct or indirect) requires further investigations.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems

Summary The covalent binding of tritiated benzo(a) pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP with DNA) and the biologically most relevant system (in vivo).Presented in part at the 10th Annual Meeting of the Union of Swiss Societies of Experimental Biology, Experientia34, 925 (1978), abstract.Acknowledgment. We thank Dr G. Kistler, Institute of Anatomy, University of Zurich, for generously supplying the SIRC and VERO cell lines, and Mr P. Manser for the preparation of the granuloma pouch fibroblasts.