acid-phosphatase and Fatty-Liver

Liver X receptor (LXR) is a member of the nuclear receptor superfamily, and it regulates various biologic processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver diseases. In the present study, we evaluated the effects of three cinnamamide derivatives on ligand-induced LXRα activation and explored whether these derivatives could attenuate steatosis in mice. N-(4-trifluoromethylphenyl) 3,4-dimethoxycinnamamide (TFCA) decreased the luciferase activity in LXRE-tk-Luc-transfected cells and also suppressed ligand-induced lipid accumulation and expression of the lipogenic genes in murine hepatocytes. Furthermore, it significantly attenuated hepatic neutral lipid accumulation in a ligand-induced fatty liver mouse system. Modeling study indicated that TFCA inhibited activation of the LXRα ligand-binding domain by hydrogen bonding to Arg305 in the H5 region of that domain. It regulated the transcriptional control exerted by LXRα by influencing coregulator exchange; this process involves dissociation of the thyroid hormone receptor-associated proteins (TRAP)/DRIP coactivator and recruitment of the nuclear receptor corepressor. These results show that TFCA has the potential to attenuate ligand-induced lipogenesis and fatty liver by selectively inhibiting LXRα in the liver.

Topics: Acid Phosphatase; Adipogenesis; Animals; Cell Line; Cinnamates; Fatty Liver; Hepatocytes; Isoenzymes; Ligands; Lipid Metabolism; Lipogenesis; Liver X Receptors; Male; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors; Tartrate-Resistant Acid Phosphatase; Transfection; Triglycerides

Polychlorinated biphenyls (PCBs) are environmental pollutants known to act as xenoestrogens. PCBs and diethylphthalate (DEP) are ubiquitous environmental pollutants because both are used as plasticizers and in various other industrial applications. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP and PCB in 21-day-old male and female pups of Wistar rats. Healthy young male and female albino rats of Wistar strain weighing 75-100g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed a normal diet and water ad libitum. Group II and III male and female rats were given PCB (Clophen A60) and DEP dissolved in corn oil mixed with the diet at 50 mg/kg of the diet (2.85 mg/kg body wt) individually to each group. Group IV male and female rats received a mixture of DEP and PCB (Clophen A60), each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet (2.85 mg/kg body wt). Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP and PCB was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of adults. The pups from each group were then segregated on the basis of their sex. Six male and female pups each (approx. 21 days old) from each group were chosen randomly and were killed for toxicity study. Liver-to-body weight ratio showed significant increase in the male and female pups of PCB- and PCB+DEP-treated rats, whereas male pups of DEP alone treated rats showed significant increase and female pups showed significant decrease as compared to controls and other treated groups. Significant increase in liver and serum lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity in the male and female pups of the three treated groups was observed. Alkaline phosphatase (ALP) activity was significantly increased only in the serum of male and female pups of the three treated groups, whereas significant decrease in the liver of male pups of the three treated groups. In the female pups, significant decrease in liver ALP was observed only PCB- and PCB+DEP-treated groups. Histology of liver showed severe vacuolation and steatosis in the hepatocytes of PCB-treated male and female pups and in PCB+DEP-treated group, vacuolation, and steatosis was much more predominant as compared to the PCB and DEP alone treated groups. DEP alone treated groups, both male and female pups showed mild vacuolation

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Drug Synergism; Drug Therapy, Combination; Environmental Exposure; Environmental Pollutants; Fatty Liver; Female; L-Lactate Dehydrogenase; Liver; Male; Organ Size; Phthalic Acids; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Reproduction; Toxicity Tests

The incidence of steatosis in livers retrieved for organ transplantation is up to 30%. Due to the shortage of donor organs, many of these livers are accepted for clinical transplantation, although a high rate of graft dysfunction is associated with ischemic preservation of steatotic livers. The present study was intended to reduce the ischemia/reperfusion injury of steatotic grafts by the use of venous systemic oxygen persufflation during cold storage.. A histologically-documented mild to moderate steatosis was induced in livers of Wistar rats by fasting for 2 days and subsequent feeding of a fat-free diet enriched in carbohydrates. Fatty livers were retrieved and flushed via the portal vein with 60 ml of HTK. In group A, livers were then stored ischemically at 4 degrees C for 24 h. Livers of group B were additionally connected to a gaseous oxygen supply and persufflated with O2 via the venous vascular system during the cold storage period. Viability of the livers was then assessed upon isolated perfusion in vitro with oxygenated Krebs-Henseleit buffer.. Venous systemic oxygen sufflation resulted in a relevant and significant reduction of parenchymal (ALT: 132+/-90 vs 434+/-172 U/l; p<0.01) and mitochondrial (GLDH: 116+/-57 vs 633+/-241 U/l; p<0.001) enzyme release during reperfusion. Moreover, Kupffer cell activation, as evaluated from acid phosphatase activity in the perfusate, was reduced to about 1/3 (4.0+/-1.3 vs 11.9+/-5.3 U/l; p<0.01). Electron microscopic analysis revealed that the liver mitochondria and sinusoidal endothelial lining were better preserved after oxygen persufflation, which was in line with the data on enzyme release and the increased portal perfusion pressure in the untreated group, while normal values were found after venous systemic oxygen sufflation.. Venous oxygen persufflation may thus represent a useful tool for the safe and improved preservation of ischemia-sensitive steatotic livers.

Topics: Acid Phosphatase; Animals; Cryopreservation; Fatty Liver; Kupffer Cells; Liver; Liver Transplantation; Male; Mitochondria, Liver; Organ Preservation; Oxygen; Perfusion; Portal Vein; Rats; Rats, Wistar; Reperfusion Injury; Venous Pressure

Abundant fat in the liver has been implicated in poor outcome after liver transplantation or liver surgery, but the reasons for this association are still unclear. The aim of the present study was to examine mechanisms that may be involved in hepatic dysfunction after ischemia-reperfusion (I/R) of the steatotic rat liver. Steatosis was produced by a choline-methionine-deficient (CMDD) diet. In the first experiment, isolated perfused rat livers, subjected to 24-hour cold storage followed by 120-minute reperfusion, were used to investigate hypothermic I/R injury of the steatotic rat liver. In the second experiment, livers were subjected to 60-minute partial left lobar vascular clamping to allow study of normothermic I/R injury. In the first experiment, compared with normal nonsteatotic liver, steatotic livers showed significantly greater injury, as assessed by amounts of hepatic enzymes released into the perfusate, bile production, the concentrations of reduced glutathione (GSH) in the perfusate, as well as in the livers themselves, and electron microscopic findings of sinusoidal microcirculatory injury. The addition of N-acetylcysteine (NAC), a precursor of glutathione, to the liver before cold storage significantly improved these parameters in steatotic livers. The second experiment showed that, compared with nonsteatotic livers, steatotic livers had lower concentrations of GSH and impaired rates of bile production. There was also evidence of increased oxidative stress in polymorphonuclear leukocytes (PMNLs) in liver or peripheral blood of rats with fatty livers. An anti-rat intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody inhibited neutrophil infiltration into pericentral sinusoids and improved these parameters in the steatotic rats. We conclude that sinusoidal microcirculatory injury is involved in hypothermic I/R injury, that oxidative stress produced by PMNLs is involved in normothermic I/R injury, and that NAC and anti-rat ICAM-1 monoclonal antibody restore liver integrity in I/R injury.

Topics: Acetylcysteine; Acid Phosphatase; Alanine Transaminase; Animals; Antibodies, Monoclonal; Aspartate Aminotransferases; Bile; Choline Deficiency; Fatty Liver; In Vitro Techniques; Intercellular Adhesion Molecule-1; Ischemia; L-Lactate Dehydrogenase; Liver; Male; Malondialdehyde; Methionine; Microscopy, Electron; Neutrophils; Perfusion; Rats; Rats, Wistar; Reperfusion Injury

Lipid peroxidation has been induced by means of an atherogenic diet causing hypercholesterolaemia, hypertriglyceridaemia, increased LDL and decreased HDL serum fractions in addition to the fatty degeneration, vacuolization of the liver cells and accumulation of malondialdehyde in the liver. Increased release of acid phosphatase and N-beta-glucuronidase was also observed pointing to cholesterol-induced lysosomal membrane damage. In response to pretreatment with, and simultaneous administration of, 6,6'-methylene bis (2,2-dimethyl-4-methane sulphonic acid sodium salt-1,2-dihydroquinoline) the signs and symptoms of fatty liver degeneration, the tissue, plasma and platelet malondialdehyde concentrations and the LDL serum fraction significantly decreased and HDL serum fraction increased. Lisosomal membrane stability was restored, resulting in physiological acid phosphatase and N-beta-glucuronidase activities. The pathological and clinical aspects of lipid peroxidation in several diseases of the digestive organs and the suggested therapeutic uses of non-toxic radical scavengers have been outlined.

Topics: Acid Phosphatase; Animals; Antioxidants; Arteriosclerosis; Cell Membrane Permeability; Cholesterol; Cholesterol, Dietary; Fatty Liver; Glucuronidase; Lipid Peroxides; Lipoproteins, LDL; Liver; Lysosomes; Male; Malondialdehyde; Quinolines; Rabbits; Triglycerides

The effect of high-protein pyridoxine-deficient diet on the localization of lysosomes and acid phosphatase activity in the rat liver was studied using light and electron microscopy. Numerous lysosomes containing lipid droplets appeared to arise directly from GERI (Golgi apparatus, endoplasmic reticulum and lysosomes) near bile canaliculi and thereafter large crystal clefts were frequently found in these lysosomes. The increase appearance of lysosomes in hepatocytes was compatible with increased lipid droplets and represented an indication of breakdown of stored lipids. Acid phosphatase activity was localized almost exclusively in lysosomes with or without lipid droplets. We postulated that one of the causes of accumulation of lipid in hepatocytes, including that of triglyceride and cholesteryl ester, might be associated with a relative deficiency of intralysosomal digestion in these conditions.

Topics: Acid Phosphatase; Animals; Dietary Proteins; Fatty Liver; Lipase; Lipid Metabolism; Lysosomes; Male; Rats; Rats, Inbred Strains; Vitamin B 6 Deficiency

In order to examine a role of lysosomes in the pathogenesis of fatty livers, analysis was made on possible etiologic factors, clinical signs and symptoms as well as laboratory data of routine liver function tests in 32 subjects with fatty livers. Of 18 cases, enzyme activities of serum acid phosphatase (Acp), beta-glucuronidase (betaG) and n-acetyl-beta-glucosaminidase (nbetaG) were measured and compared with those obtained in 20 normal subjects. Subjective symptoms were observed in 75% of the cases examined, liver swelling in 56%, positive GOT, GPT and BSP retention were in 59, 75 and 68%, respectively. The activity of serum lysosomal enzymes such as Acp, betaG and nbetaG were significantly increased and their incidence was 28, 89 and 78%, respectively. In animal experiments, activities of these enzymes in both serum and liver homogenate were examined in rats with choline-deficient, ethionine-treated, and alcoholic fatty livers. Results obtained were as follows: 1) Lysosomal enzyme activity in sera and livers of choline-deficient rats showed a significant decrease in lysosome-rich fraction and a significant increase in supernatant fraction and sera. 2) The enzyme activity in ethionine-treated rats decreased significantly in lysosome-rich fraction and tended to increase in supernatant fraction. The activity of betaG in sera increased markedly. 3) In rats given ethanol for 4 weeks, the enzyme activity of sera and liver homogenates significantly increased in lysosome-rich fraction. These results indicate that the analysis of serum lysosomal enzyme activity, in the light of clinical features and laboratory data of routine liver function tests, is useful for the diagnosis of the fatty liver. A discussion is given of a possible mode of variation of lysosomal enzymes in rats with fatty livers.

Topics: Acid Phosphatase; Adolescent; Adult; Animals; Choline; Ethionine; Fatty Liver; Fatty Liver, Alcoholic; Female; Glucuronidase; Hexosaminidases; Humans; Liver; Lysosomes; Male; Middle Aged; Rats

Recent studies from our laboratory are described which deal with endocrine cells (insulinoma, beta-cells of the pancreas, thyroid epithelial cells), pancreatic exocrine cells, and hepatocytes. These emphasize the importance of the hydrolase-rich specialized region of endoplasmic reticulum, known as GERL, in secretory cells. Also reviewed in this paper are the varied molecular transformations which apparently occur in GERL in different cell types, as reported from other laboratories as well as our own. Evidence of the continuity of GERL with rough endoplasmic reticulum is presented. Two hydrolytic enzyme activities in GERL, in addition to acid phosphatase activity, are recorded. Finally, the use of cytochemical staining procedures in the study of microperoxisomes is briefly described.

Topics: Acid Phosphatase; Adenoma, Islet Cell; Animals; Cricetinae; Duodenum; Endoplasmic Reticulum; Epithelial Cells; Fatty Liver; Ganglia, Spinal; Golgi Apparatus; Guinea Pigs; Islets of Langerhans; Liver; Microbodies; Neurons; Organoids; Pancreas; Rabbits; Rats; Thiamine Pyrophosphatase; Thyroid Gland

Comparative histochemical investigations of the livers and kidneys of female Sprague-Dawley rats were made: 1. after intoxication with O-pinacolyl-methyl-phosphonylfluoride (Soman), O,O-diethyl-O-p-nitrophenylphosphate (Paraoxon, E 600); 2. after starvation of 24 to 36 h; 3. after hypoxia for 24 h. From the results it is concluded that the fatty degeneration of liver and kidney after PE.-intoxication is caused by intracellular hypoxia. No fatty degeneration of the organs was observed following deprivation of food for 36 h. A decreased level of cholin which might be caused by the intoxication with PE., and which could be the reason for the fatty degeneration was not found. This was indicated by the unaltered evidence of phosphatids in the intoxicated animals.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cytochrome Reductases; Electron Transport Complex IV; Esterases; Fatty Liver; Female; Glucose-6-Phosphatase; Glucosephosphate Dehydrogenase; Glucuronidase; Hydroxybutyrate Dehydrogenase; Hypoxia; Isocitrate Dehydrogenase; Ketoglutarate Dehydrogenase Complex; Kidney; Lipase; Lipid Metabolism; Liver; Malate Dehydrogenase; Organophosphorus Compounds; Paraoxon; Pyruvate Dehydrogenase Complex; Rats; Soman; Starvation; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholestasis; Cholinesterases; Clinical Enzyme Tests; Diagnosis, Differential; Ethionine; Fatty Liver; Fructose-Bisphosphate Aldolase; Fructosephosphates; Necrosis; Phenobarbital; Proadifen; Rats; Thioacetamide

Topics: Acid Phosphatase; Acute Disease; Adenosine Triphosphatases; Adult; Aged; Alcoholism; Alkaline Phosphatase; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis; Chronic Disease; Enzymes; Fatty Liver; Female; Hepatitis A; Histocytochemistry; Humans; Hydroxybutyrate Dehydrogenase; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

Topics: Acid Phosphatase; Alkaline Phosphatase; Biopsy; Diabetes Mellitus; Fatty Liver; Glutamate Dehydrogenase; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Liver; Liver Diseases; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Bile Pigments; Biopsy; Central Nervous System; Chemical and Drug Induced Liver Injury; Copper; Esterases; Fatty Liver; Female; Glutamate Dehydrogenase; Hemolysis; Histocytochemistry; Liver; Liver Diseases; Necrosis; Organ Size; Sheep; Sheep Diseases; Succinate Dehydrogenase; Sulfates

Topics: Acid Phosphatase; Animals; Choline Deficiency; Chromatography, Thin Layer; Fatty Liver; Hydrogen-Ion Concentration; Lipase; Lipids; Liver; Male; Microscopy, Electron; Mitochondria, Liver; Rats; Triglycerides

Topics: Acid Phosphatase; Adolescent; Child; Child, Preschool; Chronic Disease; Esterases; Fatty Liver; Glycerolphosphate Dehydrogenase; Hepatitis; Histocytochemistry; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Liver Diseases; Malate Dehydrogenase; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Choline; Fatty Liver; Liver; Orotic Acid; Rats; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alcoholic Beverages; Alkaline Phosphatase; Biopsy; Dihydrolipoamide Dehydrogenase; Fatty Liver; Histocytochemistry; Humans; Inclusion Bodies; L-Lactate Dehydrogenase; Liver; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adult; Alanine Transaminase; Alkaline Phosphatase; Blood Cell Count; Blood Glucose; Clinical Enzyme Tests; Coronary Disease; Diet; Dietary Fats; Fasting; Fatty Liver; Hematocrit; Hemoglobins; Humans; L-Lactate Dehydrogenase; Life Support Systems; Male; Metals; Osmolar Concentration; Time Factors; Triglycerides

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Choline Deficiency; Electron Transport Complex IV; Esterases; Fatty Liver; Histocytochemistry; Lipase; Liver; Liver Glycogen; Liver Regeneration; Methods; Protein Deficiency; Rats; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Carbon Tetrachloride Poisoning; Depression, Chemical; Fatty Liver; Lipid Metabolism; Liver; Liver Regeneration; Pyridoxine; Rats; Riboflavin; Thiamine

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Chlorine; Depression, Chemical; Fatty Liver; Injections, Intramuscular; Lipid Metabolism; Liver; Prednisone; Rats; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Choline Deficiency; Electron Transport Complex IV; Esterases; Fats; Fatty Acids; Fatty Liver; Glycogen; Histocytochemistry; Liver; Phospholipids; Protein Deficiency; Rats; Succinate Dehydrogenase; Time Factors

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Bile Ducts, Intrahepatic; Cholestasis; Electron Transport Complex IV; Fatty Liver; Female; Glucose-6-Phosphatase; Histocytochemistry; Hydroxybutyrate Dehydrogenase; L-Lactate Dehydrogenase; Male; Monoamine Oxidase; Oxidoreductases; Rabbits

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carnitine; Choline; Fatty Liver; Liver; Rats

Topics: Acid Phosphatase; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cytoplasm; Electrons; Fatty Liver; Hepatitis; Histocytochemistry; Humans; Liver; Lysosomes; Microscopy; Microscopy, Electron; Rats; Research

Topics: Acid Phosphatase; Animals; Carbon Tetrachloride Poisoning; Cathepsins; Chemical and Drug Induced Liver Injury; Fatty Liver; Glucuronidase; In Vitro Techniques; Liver; Lysosomes; Rats; Ribonucleases; Subcellular Fractions; Sulfatases; Urate Oxidase