The effect of carbon tetrachloride on the lipoproteins of rat-liver cell sap and serum

1. The lipoproteins of the liver cell sap can be resolved by paper electrophoresis into five components. Almost two-thirds of the total lipid, cholesterol and phospholipid are present in the slowest- and the fastest-moving components. 2. There is a two- to three-fold increase in the lipid content of the liver cell sap after the administration of carbon tetrachloride. 3. The cholesterol and phospholipid contents of the serum alpha- and beta-lipoproteins separated by paper electrophoresis fall after treatment with carbon tetrachloride, whereas the total lipid content of that fraction that remains at the origin rises.     

Effect of a new herbo-mineral hypolipidemic agent on plasma lipoprotein pattern in rat atherosclerosis

Hyperlipidemia was induced in rats by feeding an atherogenic diet for 5 months. The effect of administration of an indigenous hypolipidemic agent, Anna Kaara Raaja Sindhooram (AKRS) on the plasma lipoprotein profile was studied in the presence and absence of dietary lipid stimuli. Hyperlipidemia produced an enormous increase in the cholesterol and triglyceride contents of the low density (LDL) and very low density (VLDL) lipoprotein fractions and reduced the level of the putative non-atherogenic high density cholesterol (HDL-C). The agarose gel electrophoretic pattern showed a decrease in alpha-lipoproteins and an increase in beta-lipoproteins in the hyperlipidemic rats. AKRS treatment for 5 months altered the lipoprotein pattern favourably by raising HDL-C and lowering LDL-C in the treated rats.     

Tumor and body interrelationships in 14C-thiamine utilization

Variations in the content of 14C-thiamine, thiamine-dependent enzyme transketolase (TK), and thiamine diphosphate (TDP) in mouse tissues were studied during Ehrlich's ascites tumour growth. The concentration of TDP in the liver of tumour-bearing animals continuously drops during 10 days after inoculation, TDP level in the tumour itself decreases more abruptly by the terminal period of tumour growth (the 10th day). At the same time the tumour demonstrates sharp deficiency of the coenzyme and redundance of apoenzymatic forms of TK. The growing deficiency of thiamine in the tumour favours greater tension of thiamine metabolism and appearance of competitive tumour-host interrelationships that are most pronounced in the presence of hypovitaminosis.     

Effect of short-term or intermittent hypobaric hypoxia on plasma lipids in young rats

Changes in the level of plasma lipids (cholesterol, fatty acids and lipoproteins) were followed in young rats exposed once or repeatedly to hypobaric hypoxia. A single exposure to hypoxia increased the level of LDL lipoproteins but did not influence the concentration of cholesterol and fatty acids in 18-day-old rats. Repeated exposure to hypobaric hypoxia caused a statistically significant increase in the concentration of cholesterol, fatty acids, chylomicra, low density beta-lipoproteins (LDL) and very-low-density beta-lipoproteins (VLDL) in 18-day-old rats, while the level of high-density alpha-lipoproteins (HDL) decreased. In animals that had been repeatedly exposed to hypoxia in their youth, a significant decrease of the LDL lipoprotein fraction was observed at the age of 108 days.     

Apolipoprotein A-I gene expression is upregulated by polychlorinated biphenyls in rat liver

Xenobiotics such as polychlorinated biphenyls (PCB) increase serum cholesterol level (especially high density lipoprotein cholesterol) and apolipoprotein A-I (apo A-I) level in rats. The effect of PCB on serum apo A-I and hepatic apo A-I gene expression and the relationship between apo A-I and drug-metabolizing enzymes in rats were investigated. Serum levels of cholesterol and apo A-I were increased by dietary addition of PCB in a dose-dependent manner (0-500 mg/kg diet). Hepatic apo A-I mRNA level was also elevated by PCB in a similar fashion. Serum level of cholesterol gradually increased during feeding period of PCB (200 mg/kg diet, 105 days) and reached a two-fold higher level in PCB group than in controls. The levels of serum apo A-I and hepatic apo A-I mRNA linearly elevated during feeding period of PCB and were increased 3- or 4-fold, respectively, compared to controls. Although acute administration (16 hr) of PCB, 3-methylcholanthrene, and phenobarbital induced cytochrome P-450 gene expression in the liver, hepatic apo A-I gene expression was not increased by these xenobiotics. These results indicated that the serum levels of cholesterol and apo A-I had positive correlation with hepatic level of apo A-I mRNA in rats fed PCB, and that hepatic apo A-I gene expression was dependent upon intake of PCB but was not directly related to the induction of drug-metabolizing enzymes. This study demonstrated that xenobiotic-induced hyper-alpha-cholesterolemia would be caused by the increased apo A-I gene expression and cholesterol synthesis in the liver, coordinately.     

Effect of hyperimmunization with tick-borne encephalitis virus on lipid metabolism

Prolonged administration to rabbits of the brain tissue of albino mice and of the cell culture of chick embryo with and without the tick-borne encephalitis virus was accompanied by the changes in the qualitative fatty acid composition in the blood serum in the direction of increase of the polyunsaturated compounds; iodine number increased in the liver. A five-cycle immunization with the virus-containing material and with the brain tissue led to the rise in the content of blood serum beta-lipoproteins. The noted deviations were more pronounced in using the tick-borne encephalitis virus. Hyperimmunization with the virus-containing antigen promoted elevation of the lipolytic activity of the blood serum and of the liver tissue.     

Molecular mechanisms of thiamine utilization

Thiamine is required for all tissues and is found in high concentrations in skeletal muscle, heart, liver, kidneys and brain. A state of severe depletion is seen in patients on a strict thiamine-deficient diet in 18 days, but the most common cause of thiamine deficiency in affluent countries is alcoholism. Thiamine diphosphate is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. The enzymes are important in the biosynthesis of a number of cell constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses and in biosyntheses and for synthesis of pentoses used as nucleic acid precursors. Because of the latter fact, thiamine utilization is increased in tumor cells. Thiamine uptake by the small intestines and by cells within various organs is mediated by a saturable, high affinity transport system. Alcohol affects thiamine uptake and other aspects of thiamine utilization, and these effects may contribute to the prevalence of thiamine deficiency in alcoholics. The major manifestations of thiamine deficiency in humans involve the cardiovascular (wet beriberi) and nervous (dry beriberi, or neuropathy and/or Wernicke-Korsakoff syndrome) systems. A number of inborn errors of metabolism have been described in which clinical improvements can be documented following administration of pharmacological doses of thiamine, such as thiamine-responsive megaloblastic anemia. Substantial efforts are being made to understand the genetic and biochemical determinants of inter-individual differences in susceptibility to development of thiamine deficiency-related disorders and of the differential vulnerabilities of tissues and cell types to thiamine deficiency.     

The control of cholesterol metabolism and plasma lipid levels in infant rats.

Infant rats received an i.p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethasone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexamethasone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol.     

The behavior of lipoproteins, cholesterol, triglycerides, free fatty acids and free glycerol in serum of rats with experimental hyperthyroxinemia and hypothyreosis]

In hyperthyroxinemic and hypothyreotic rats the lipoprotein level in serum was investigated using agarosegel-electrophoresis and changes in serum level of cholesterol, triglycerides, free fatty acids and glycerol were determined. In hyperthyroxinemic animals the beta-lipoproteins were found in the same level as the control animals, while the prae-beta-fraction was significantly elevated and the alpha-lipoproteins lowered. The cholesterol was significantly reduced, the triglycerides and the glycerol significantly increased. The free fatty acids were slightly elevated. In hypothyreotic animals the beta-and prae-beta-fraction of lipoproteins was significantly elevated. The alpha-lipoproteins were found diminished. Cholesterol and triglyceride values were also significantly increased. The levels of free fatty acids and glycerol did not differ in both groups of animals.     

饲料蛋白水平对低温应激下吉富罗非鱼血清生化指标和HSP70 mRNA表达的影响

在水温27℃条件下, 分别对吉富罗非鱼(27.642.79) g投喂3组不同蛋白水平的饲料, 养殖周期56d。饲养结束后, 进行14℃低温应激实验, 研究低温应激后0-24h内, 鱼体血清生化指标与肝脏HSP70　mRNA表达量的变化。结果表明, 短期投喂50%蛋白水平的饲料可以提高罗非鱼血清中葡萄糖、总蛋白、甘油三酯与胆固醇水平以及血清谷丙转氨酶与谷草转氨酶活力。在低温应激后, 50%蛋白组血清葡萄糖、总蛋白、甘油三酯与胆固醇水平呈下降趋势, 而血清皮质醇水平与谷草转氨酶活力表现为先上升后下降变化。25%和38%蛋白组血清葡萄糖水平与谷丙转氨酶活力在应激期间呈上升趋势, 而谷草转氨酶与碱性磷酸酶活力和总蛋白与胆固醇水平呈先上升后下降变化。各实验组溶菌酶活力与肝脏HSP70 mRNA的表达量呈先上升后下降的变化。由此可知, 短期投喂高蛋白饲料可以提高罗非鱼血液中蛋白、血糖与脂肪含量, 增强鱼体抗应激能力, 同时, 高蛋白水平的饲料也会引起肝脏产生分解压力以及增加饲料成本。在生产中, 需要根据实际需要合理确定饲料的蛋白含量。       

Modulation of A and B cell functions by tolbutamide and arginine in the pancreas of thiamine-deficient rats

The effects of administration of glucose orally and tolbutamide or arginine intravenously on insulin and glucagon secretion and blood glucose level were studied in normal and thiamine-deficient rats. In thiamine deficiency, insulin secretion and glucose tolerance were impaired during glucose ingestion. Tolbutamide decreased the blood glucose level in both control and thiamine-deficient rats but its stimulatory effect on insulin secretion was minimal in thiamine-deficient rats unlike the control animals. Arginine did not alter substantially the blood glucose or insulin in thiamine-deficient rats, whereas it increased the insulin level in control rats. The fasting plasma glucagon level was high in thiamine deficiency. Tolbutamide increased the plasma glucagon in control rats, but did so only marginally in thiamine-deficient rats. Arginine also increased the glucagon secretion throughout the period of study in control rats. In thiamine-deficient rats the glucagon secretion was pronounced only after 20 min of arginine administration. These results suggest that an unimpaired glucose metabolism is a prerequisite to induce proper insulin secretion. Only proper insulin secretion can check the glucagon secretion rather than the increased glucose level. Hypoglycemia can induce glucagon secretion independent of the insulin level.     

Accumulation and release of triglycerides by rat liver following partial hepatectomy

Regenerating liver accumulates lipid for about 20 hr following partial hepatectomy. During this time incorporation of intravenously administered palmitate-9, 10-(3)H into beta-lipoprotein increased. 13 hr after partial hepatectomy, there was no change in the level of serum beta-lipoproteins, but the specific activities of the triglycerides in the liver and beta-lipoproteins were significantly diminished. Extension of these studies to the isolated perfused liver system demonstrated that 13 hr after partial hepatectomy the regenerating liver is capable of secreting greater quantities of the lipid, but not the protein, moiety of the beta-lipoproteins in comparison with liver taken immediately from a partially hepatectomized animal, although there was no difference between the weights of the livers. However following addition of palmitate-(3)H and (14)C-labeled amino acids to the perfusate, the specific activity of the hepatic and beta-lipoprotein triglycerides of the liver excised 13 hr after partial hepatectomy was diminished, but that of the protein was not affected. Prelabeling of the accumulated triglyceride with palmitate-1-(14)C in vivo revealed that the proportions of the accumulated triglyceride secreted as beta-lipoproteins by perfused livers excised immediately and 13 hr after partial hepatectomy were identical. It is concluded that regenerating liver rapidly acquires the ability to mobilize triglycerides at a rate equal to that of the much larger normal liver, so that it can handle all free fatty acids presented to it.     

Synthesis,physico-chemical properties and effect of adenosine thiamine triphosphate on vitamin B1 metabolism in the liver of alloxan diabetic rats

BackgroundAdenosine thiamine triphosphate (AThTP) is a nucleotide discovered in bacteria and some other living organisms more than a decade ago. No biochemical function for AThTP has been established yet, however, experimental data available indicate its possible involvement in metabolic regulation or cell signaling. Metabolism of AThTP in mammals, as well as the feasibility of its pharmacological application, is essentially unstudied.MethodsPreparative low-pressure chromatography was employed to purify chemically synthesized AThTP with its further analysis by mass spectrometry, HPLC, UV and fluorescence spectroscopy. Enzyme activity assays along with HPLC were used to examine the effects of AThTP and thiamine on vitamin B₁ metabolism in the liver of alloxan-induced diabetic rats.ResultsAn improved procedure for AThTP synthesis and purification is elaborated. Solution stability, optical spectral properties and the molar absorption coefficient for AThTP were determined. The levels of thiamine compounds were found to be increased in the liver of diabetic rats. Neither AThTP nor thiamine treatment affected hepatic vitamin B₁ metabolism. Fasting blood glucose concentration was also unchangeable after AThTP or thiamine administration.General significanceContrast to the widespread view about thiamine deficiency in diabetes, our results clearly shows an adaptive increase in the level of B₁ vitamers in the liver of alloxan diabetic rats with no further rising after AThTP or thiamine treatment at a moderate dose. Neither AThTP nor thiamine is effective in glycaemic control. These findings are to be considered in future studies dealing with thiamine or its analogues application to correct metabolic disturbances in diabetes.     

The dynamics of [3H]-cholesterol incorporation into the liver and aortic tissue of guinea pigs on long-term ethanol administration]

The effect of ethanol administration to guinea pigs (4 g/kg, per os) on the dynamics of [3H]-cholesterol incorporation into the liver and aorta tissues was studied for 3 months. It has been discovered that specific radioactivity of the control animals linearly increased during 24 hours in the blood serum. Ethanol reduced it as compared with the control only 0.5 h after a label has been introduced. Cholesterol renovation in the liver remained unchanged under the prolonged effect of ethanol. In the aorta the ethanol effect was characterized by a decrease of [3H]-cholesterol specific radioactivity 0.5 h after its administration. However, in this case the ratio of aorta/blood serum radioactivity increased. A day after the labelled cholesterol administration to alcoholized animals the radioactivity calculated per 1 mg of cholesterol and per unit of tissue weight and referred to the blood serum radioactivity was lower as compared to the control level.     

The role of catecholamines and glucagon on serum and liver metallothionein response to restraint stress

The role of glucagon and catecholamines on serum and liver metallothionein (MT) concentrations in basal and stress conditions has been studied. Glucagon showed no effect on serum MT either in basal (unstressed) or stress (20 hours of restraint) conditions. In contrast, glucagon administration increased both unstressed and stressed levels of liver MT. No effect of the alpha + beta-catecholamine blocker labetalol on serum MT levels was observed in unstressed rats. However, the administration of labetalol abolished the increase in serum MT levels caused by stress. These data suggest that catecholamines might be involved in serum MT regulation during stress, while they might not be important in the maintenance of basal serum MT levels. Finally, no significant effect of adrenergic blockade was found on basal and stress levels MT, in agreement with previous data from this laboratory.     

Effect of methotrexate on long-chain fatty acid metabolism in liver of rats fed a standard or a defined, choline-deficient diet

The effect of methotrexate on lipids in serum and liver and key enzymes involved in esterification and oxidation of long-chain fatty acids were investigated in rats fed a standard diet and a defined choline-deficient diet. Hepatic metabolism of long-chain fatty acids were also studied in rats fed the defined diet with or without choline. When methotrexate was administered to the rats fed the standard diet there was a slight increase in hepatic lipids and a moderate reduction in the serum level. The palmitoyl-CoA synthetase activity and the microsomal glycerophosphate acyltransferase activity in the liver of rats were increased by methotrexate. The data are consistent with those where the liver may fail to transfer the newly formed triacylglycerols into the plasma with a resultant increase in liver triacylglycerol content and a decrease in serum lipid levels. Fatty liver of methotrexate-exposed rats can not be attributed simply to a reduction of fatty acid oxidation as the carnitine palmitoyltransferase activity was increased. The methotrexate response in the rats fed the defined choline-deficient diet was different. There was a reduction in both serum and hepatic triacylglycerol and the glycerophosphate acyltransferase and palmitoyl-CoA synthetase activities. The carnitine palmitoyltransferase activity was unchanged. Hepatomegaly and increased hepatic fat content, but decreased serum triacylglycerol, total cholesterol and HDL cholesterol were found to be related to the development of choline deficiency as the pleiotropic responses were almost fully prevented by addition of choline to the choline-deficient diet. Addition of choline to the choline-deficient diet normalized the total palmitoyl-CoA synthetase and carnitine palmitoyltransferase activities. In contrast to methotrexate exposure, choline deficiency increased the mitochondrial glycerophosphate acyltransferase activity. The data are consistent with those of where fatty liver induction of choline deficiency may be related to an enhanced esterification of long-chain fatty acids concomitant with a reduction of their oxidation.     

Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.     

Effect of estrogens on β-hydroxy-β-methylglutaryl coenzyme a reductase activity and cholesterol levels

The effect of estrogens on hepatic β-hydroxy-β-methylglutaryl coenzyme A reductase activity and cholesterol in serum and liver of ovarietcomized rats on normal diet, 2% cholestyramine diet or 2% cholesterol diet was investigated. Estrogen administration to ovariectomized rats on normal diet resulted in increased reductase activity and was correlated with decreased serum cholesterol and increased liver cholesterol levels wlth mestranol (ME), ethinyl estradiol (EE) and estradiol benzoate (EB, 250 μg) but increased serum and liver cholesterol levels with 25 μg and 100 μg EB administration. The increased stimulation of reductase activity by estrogen administration was absolished when rats were fed a 2% cholesterol diet. Cholestyramine feeding markedly increased reductase activity in livers of ovariectomized rats. These studies show that estrogens are not absolutely required for the stimulation of reductase activity and therefore is consistent with the model in which cholesterol functions as a feedback repressor of reductase activity.     

Seasonal fluctuation in lipid and cholesterol content of ovary, liver and blood serum in relation to annual sexual cycle in Heteropneustes fossilis (Bloch).

Seasonal fluctuation in lipid content of ovary and liver and cholesterol content of ovary, liver and serum in relation to annual reproductive cycle in H. fossilis has been worked out. Reduction in lipid content of liver was associated with decrease in hepatosomatic index (HSI) in prespawning and spawning phases. But there was an obvious increase in the lipid level of ovary in the above phases which coincided with enhanced gonadosomatic index (GSI) records. Serum and ovary showed a subsidence in their cholesterol contents in prespawning followed by increased level during spawning period. Substraction in liver cholesterol started in prespawning and continued till spawning phase and thereafter regained upward trend. Lipid and cholesterol levels in all organs studied along with GSI and HSI returned to initial values by the end of postspawning stage. Administration of clomid, sexovid, PGE1 and PGF2 alpha for a week did not induce any change in HSI, GSI, lipid and cholesterol values of liver and serum. However, these drugs were effective in suppressing the ovarian cholesterol within a week. The above drugs seem to affect cholesterol level indirectly since they trigger gonadotrophin secretion which in turn probably accelerated cholesterol utilization in ovary for increased steroid hormone output.     

The mechanism of lack of hypocholesterolemic effects of pravastatin sodium,a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,in rats

In order to clarify the reason why pravastatin, a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, did not show hypocholesterolemic effects in rats, the changes of various parameters affecting the serum cholesterol levels by pravastatin were determined in rats and rabbits, as a comparison. In rabbits, pravastatin administration at 50 mg/kg for 14 days decreased serum and liver cholesterol by 40% and 8%, respectively. The hepatic LDL receptor activity was increased 1.7-fold, and VLDL cholesterol secretion was decreased. Cholesterol 7α-hydroxylase activity was not changed. In contrast, in rats, serum cholesterol was increased by 14% at 50 mg/kg and 27% at 250 mg/kg for 7 days, respectively. At 250 mg/kg, liver cholesterol was significantly increased by 11%. Under these conditions, neither the hepatic LDL receptor activity nor cholesterol 7α-hydroxylase was changed, and VLDL cholesterol secretion was increased. At 250 mg/kg, net cholesterol synthesis in rat liver was increased after 7 days of consecutive administration. These results imply that in rats, stimulated net cholesterol synthesis caused the increase of liver cholesterol followed by the increase of VLDL cholesterol secretion, and resulted in the raise of plasma cholesterol. Although hepatic HMG-CoA reductase was induced almost the same fold in both animals at 50 mg/kg, the induced HMG-CoA reductase activity in rats might overcome the inhibitory capability of pravastatin, resulting in an increase of net cholesterol synthesis, but not in rabbits. This overresponse to pravastatin in rats might cause the lack of hypocholesterolemic effects of this drug.