Effects of long-term feeding of glibenclamide on normal rats

Summary Prolonged administration of glibenclamide decreased blood sugar, liver glycogen and protein and increased liver and serum lipids and organic phosphates of liver in normal rats. A significant weight increase observed in glibenclamide group of rats is attributed to lipid accumulation.     

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.     

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).     

Studies on the biochemical effects of glibenclamide on alloxan diabetic rabbits

Summary Treatment of alloxan diabetic rabbits with glibenclamide, the most potent of the sulfonylureas, for a period of 2 months, significantly ameliorated the diabetic condition. It produced a decrease in serum and liver lipids, amino acids, serum urea, blood sugar and urine sugar; increase in body weight, serum and liver proteins, liver glycogen, glucose tolerance and serum and liver acid labile phosphates. The possible mechanism of action of this hypoglycemic agent is discussed.     

Studies on the biochemical effects of glibenclamide on alloxan diabetic rabbits

Treatment of alloxan diabetic rabbits with glibenclamide, the most potent of the sulfonylureas, for a period of 2 months, significantly ameliorated the diabetic condition. It produced a decrease in serum and liver lipids, amino acids, serum urea, blood sugar and urine sugar; increase in body weight, serum and liver proteins, liver glycogen, glucose tolerance and serum and liver acid labile phosphates. The possible mechanism of action of this hypoglycemic agent is discussed.     

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.     

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

Summary 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.     

Occurrence of polyploidy and multinuclearity in the differentiating liver of chick embryo

Summary Increase in nuclear size in liver has been used as an index of polyploidy. It has long been considered that the occurrence of polyploidy and multinuclearity are characteristics of mammalian liver. The present study shows the occurrence of these phenomena in the liver of birds, so these features are not confined to mammals. 3 classes of nuclear size groups have been identified. The simultaneous occurrence of polyploidy and binuclearity indicates some sort of interrelationship between them.     

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     

Cytochalasin D is able to mimic the effects of phalloidin on the rat liver

Cytochalasin D induces a strong potassium release in the isolated perfused rat liver and leads to vacuolization of the liver parenchymal cells. These effects are similar to the action of phalloidin on the rat liver. Since phalloidin and cytochalasin act in a different way on microfilaments, it is suggested that any disturbance of the function of microfilaments can induce these effects.     

Effect of aminoglutethimide on murine fetal hepatic erythroid colony formation

Pretreatment of pregnant mice with aminoglutethimide phosphate, an inhibitor of glucocorticoid synthesis, increases the content of fetal liver erythroid colony-forming cells (CFU-E), as assessed by the formation of erythroid colonies in vitro by fetal liver cells in plasma clots containing exogenous erythropoietin. In addition, the inability of aminoglutethimide to influence erythroid colony formation in vitro suggests that endogenous glucocorticoids exert a suppressive effect on the number of functional CFU-E in the fetal liver.     

Effect of vitamin A deficiency on the levels of glutathione and glutathione-S-transferase activity in rat lung and liver

Summary Vitamin A deficiency reduces the content of glutathione in liver and lung. Also, glutathione S-transferase activity is decreased significantly in the lung, whereas its activity is increased in the liver.     

Effect of vasectomy on hepatic drug metabolism

2 months after bilateral vasectomy the metabolism of aniline but not aminopyrine was increased in rat liver homogenates, whereas vasectomy did not affect the metabolism of either compound in guinea-pig liver homogenates.     

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.     

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.     

Stimulation of cell division in ectopic liver tissue following partial removal of the lung.

Autografts of liver were implanted into the left lung (Xenopus laevis). Subsequent removal of the right lung stimulated increased mitotic activity in the lung and in the liver graft.     

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.     

Effect of thyroid hormone on somatomedin-C release from perfused rat liver

The effect of thyroid hormone on plasma somatomedin-C (SmC) level and on SmC release from perfused rat liver was investigated. Plasma SmC levels and liver tissue SmC were significantly increased in thyroxine-treated rats. Physiological doses of triiodothyronine increased SmC release and SmC concentration in the perfused rat liver. These results indicate that thyroid hormone directly enhances the synthesis and release of SmC in the rat.