Serum half-life, distribution, hepatic uptake and biliary excretion of alpha-tocopherol in rats

The serum clearance of alpha-[3H]tocopherol has been studied after intravenous injection of intestinal lymph labeled in vivo with radioactive alpha-tocopherol. The half-life of the injected alpha-[3H]tocopherol was approx. 12 min. Fractionation of plasma by ultracentrifugation 10 min after injection of lymph showed that 91% of the radioactive alpha-tocopherol remaining in plasma was located in chylomicrons (d less than 1.006 g/ml) and 7.8% in high-density lipoproteins (HDL, 1.05 less than d less than 1.21 g/ml). 2 h after administration of alpha-tocopherol, about 35% of the radioactivity recovered in plasma was associated with chylomicrons and approx. 51% with HDLs. alpha-[3H]Tocopherol was initially taken up by the liver, which contained more than 50% of the injected radioactivity after 45-60 min. Separation of parenchymal and nonparenchymal cells demonstrated a preferential uptake of alpha-[3H]tocopherol by the parenchymal liver cells. After 24 h about 11% of the injected dose was recovered in the liver. Considering whole organs the liver, adipose tissue and skeletal muscle had the highest content of radioactivity after 24 h. Furthermore, about 14% of the administered dose was recovered in bile during 24 h draining.     

L-carnitine increases liver alpha-tocopherol and lowers liver and plasma triglycerides in aging ovariectomized rats

The objective of this study was to determine whether dietary L-carnitine can influence the status of alpha-tocopherol, retinol and selected lipid parameters in aging ovariectomized rats, an animal model for the menopausal state. Fourteen Fisher-344 female rats 18 months old were acclimated for 4 weeks and ovarectomized. Seven rats per treatment were assigned to either a control group fed ad libitum AIN-93M diet or a carnitine group fed the same diet supplemented with L-carnitine. After an 8-week feeding period, blood and selected tissues were taken for analyses. No differences were noted in food intake, body weight, or organ weights due to L-carnitine. Dietary carnitine significantly increased liver alpha-tocopherol and tended to increase plasma alpha-tocopherol (P<.09). No changes in alpha-tocopherol were observed in other tissues including the brain, lungs and retroperitoneal fat. Retinol levels in plasma and tissues were not affected by supplemental L-carnitine. Significant decreases in liver and plasma triglyceride (TG) levels were noted, suggesting increased utilization of fatty acids. No differences were observed in the fatty acid profile of tissues. The results provide evidence that dietary supplementation of L-carnitine enhances the alpha-tocopherol status and improves the utilization of fat leading to lowering of the liver and plasma levels of TG in aging ovariectomized rats. Whether supplemental L-carnitine may be of benefit to postmenopausal women in lowering plasma TG and improving the antioxidant status remains to be studied.     

Strongyloides ratti: Transfer of immunity in rats by lymph node cells or serum

Immune mesenteric lymph node cells (IMLNC) and hyperimmune serum, alone or in combination, were transferred to recipient, syngeneic Lewis rats. On the day of cell transfer, the recipients, along with appropriate controls, were infected with 1,000Strongyloides ratti larvae. Twelve days later, the number of adult worms in the anterior small intestine was counted and the number ofS. ratti eggs in the terminal uterus of representative female worms was determined. Using these methods, we showed that worm fecundity was reduced in the IMLNC recipients, the hyperimmune serum recipients, and the recipients of both cells and serum as compared with regular controls (averages of 2.45, 2.93, and 2.98 eggs, respectively, vs. 4.73 eggs). The number of adult worms recovered from the IMLNC recipients was not reduced (474.6 worms). However, significantly fewer worms were recovered from the recipients of IMLNC-hyperimmune serum and the recipients of hyperimmune serum only as compared with regular controls (184.8 and 171.5 worms, respectively, vs. 567.2 worms). A working hypothesis, involving an interaction of serum and cellular components, is postulated as the mechanism for this protective response.     

Transport,metabolism and distribution space of octanoate in the perfused rat liver

The scope of the present work was to investigate the metabolism and the passage of octanoate from albumin into the phospholipid bilayer of the plasma membrane and from thence into the cell space. The experiments were done in the isolated perfused rat liver with infusions of albumin and octanoate at various concentrations. Once steady-state conditions were attained, trace amounts of [1-¹⁴C]-octanoate, [¹³¹I]-albumin and [³H]-water were injected simultaneously and the effluent perfusate was fractionated. The normalized dilution curves were used for model analysis. The model which gives the best fit to the experimental results and which also produces the most consistent parameters is one that presupposes a rapid distribution of octanoate into the cell membrane and a slow transfer from the cell membrane into the cytosol. The concentration dependence of the distribution between the membrane and the extracellular space is parabolic, suggesting that octanoate changes the properties of the cell membrane when present at higher concentrations. The passage from the cell membrane into the cell space is relatively slow and limits metabolic transformation partly or totally, depending on the octanoate concentration in the plasma membrane. The rapid transfer of octanoate from the albumin space into the plasma membrane corroborates previous measurements of the dissociation of the albumin–octanoate complex. © 1997 John Wiley & Sons, Ltd.     

Effect of alpha-tocopherol on the physicochemical properties of liver cell membranes in adrenalectomized rats

The increased content of lipid peroxidation products in the liver and an associated increase in the microviscosity of lipid nuclear and microsomal liver cell membranes, as well as disturbed protein-lipid interaction in them have been determined 8 days after adrenalectomy. The addition of alpha-tocopherol into the diet (4 mg per day for 7 days after the operation) prevented the activation of lipid peroxidation and the disturbances of physico-chemical membrane properties and the decrease in the muscular working capacity in rats caused by adrenalectomy.     

Mast cells and fibrosis in compartments of lymph nodes of normal,gnotobiotic, and athymic rats

Summary Reports vary on the amount and distribution of mast cells in lymph nodes. We analysed the mast-cell population in compartments of nodes of diverse sites, from euthymic and athymic animals of various ages. Nodal mast cells were few in young animals, occurring mostly in medullary sinuses. Aging is often accompanied by a moderate increase of nodal nast cells. In compartments of a few nodes of some aged athymic and euthymic animals, the mast cells were greatly increased in the extrafollicular zone overlying medulla directly. In certain cases, this great increase was accompanied by pronounced mast-cell degranulation and by fibrosis in the mast cell-rich extrafollicular zone. It is suggested that the mast cells of medullary sinuses relate to non-immunological events, while those of the lymphoid parenchyma relate to elements that can induce humoral immune responses or are somehow involved in nodal processes of such responses. It is further suggested that an occasional emergence, with aging, of a deficiency of particular humoral immune responses may induce an excessive increase of cortical mast cells, and that activities of the resulting dense mast-cell population contribute to the onset of fibrosis.Abbreviations AUC above unit center - AUP above unit periphery - AM above medulla (directly above medulla) Funded by the Medical Research Council of Canada     

Effect of amiodarone, an antiarrhythmic drug, on serum and liver lipids and serum marker enzymes in rats.

Administration of amiodarone (AD) to rats leads to marked damage to liver, as evidenced by pathological changes and significant increases in activities of serum marker enzymes and levels of lipids like cholesterol and phospholipids with no alteration in the triglyceride levels. The risk factor, that is the total cholesterol/HDL cholesterol ratio, exhibited increase in the experimental animals, indicating that amiodarone treatment may lead to the development of coronary heart disease.     

Phospholipid hydroperoxide accumulation in liver of rats intoxicated with carbon tetrachloride and its inhibition by dietary alpha-tocopherol

The formation and accumulation of phospholipid hydroperoxides, especially of phosphatidylcholine hydroperoxide (PCOOH), a primary peroxidation product of phosphatidylcholine (PC), in livers of carbon tetrachloride-intoxicated rats was investigated. PCOOH in liver and blood plasma was measured by a chemiluminescence-high-performance liquid chromatography procedure originally developed by Miyazawa et al. (Anal. Lett. 20, 915, 1987; Free Radical Biol. Med. 7, 209, 1989). Male Sprague-Dawley rats (120 g body wt., 5 weeks of age) were used in the experiments. The amount of PCOOH in the liver of control rats (CCl4-untreated) was 160 +/- 20 pmol/100 mg protein (mean +/- SD) and the PCOOH/PC molar ratio was 1.1 +/- 0.1 X 10(-5). In CCl4 (0.1 ml/100 g body wt.)-dosed rats, the liver PCOOH was 289 +/- 65 pmol/100 mg protein (PCOOH/PC = 2.4 +/- 0.4 X 10(-5], 764 +/- 271 pmol/100 mg protein (PCOOH/PC = 5.2 +/- 1.7 X 10(-5], and 856 +/- 165 pmol/100 mg protien (PCOOH/PC = 6.0 +/- 0.8 X 10(-5] at 6 h, 24 h, and 1 week after the dose, respectively. Under such conditions, the liver phosphatidylethanolamine hydroperoxide (PEOOH) level was not altered and the concentration was less than 100 pmol/100 mg protein even after the dose. The increments of liver PCOOH were suppressed 56% by the oral supplementation of DL-alpha-tocopherol (5 mg/100 g body wt./day) for a week before CCl4 administration. A relatively larger amount of PEOOH was found after stimulation of PC hydroperoxidation in the liver of rats with a large amount of CCl4 (0.25 ml/100 g body wt.) rather than with the small amount of CCl4 (0.1 ml/100 g body wt.).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transport and intracellular distribution of components of the cortisol-asialotranscortin complex in the liver

The effect of desialation of human transcortin on the transcortin-cortisol complex transport into hepatocytes and on subsequent intracellular distribution of the complex components was studied in model experiments with perfused rat liver. It was demonstrated that in the presence of desialated transcortin the time of [3H]cortisol incubation in the perfusion medium decreased more than 200 times as compared with the native protein. [3H]cortisol and [131I]asialotranscortin trapping by hepatocytes occurs simultaneously. The content of the [3H]cortisol--[131I]asialotranscortin complex in rat liver plasma membranes reaches a maximum 3 min after beginning of perfusion. Then the intact complex is transported into lysosomes, where it dissociates with a subsequent release of asialotranscortin and cortisol metabolites into the cytoplasm.     

Characterization of serum, liver, and intestinal sialyltransferases from rats treated with colchicine

A modified high pressure liquid chromatographic method using lactose (Gal beta 1----4Glc) as an exogenous acceptor has been used to characterize the sialyltransferases known to increase in the serum of colchicine-treated rats. The results show a 10-fold increase of Gal beta 1----4GlcNAc alpha 2----6 sialyltransferase (alpha 2----6 ST), whereas the Gal beta 1----3GlcNAc alpha 2----3 sialyltransferase showed only 1.6-fold increase in the serum after 17 h of colchicine treatment. The sialyltransferase activity in serum using exogenous desialylated, alpha 1-acid glycoprotein as acceptor also showed an eightfold increase. In liver homogenate and Golgi membrane, the sialyltransferase activity when assayed with desialylated alpha 1-acid glycoprotein as acceptor showed a slight decrease after 4 h, but returned to normal level after 17 h. A similar trend was seen when the two transferases were assayed with lactose as acceptor. The antiserum to rat alpha 2----6 ST inhibited the sialyltransferase activity in serum, liver, and jejunal incubation medium. Jejunal sections from rats treated with colchicine for 4 h in presence of heated serum showed a decrease of sialyltransferase, with consequent increase of the alpha 2----6 ST enzyme activity in the medium. This result suggests that intestinal tissue could be a source of increased serum enzyme activity in colchicine treatment.     

R.hominis对肝硬化大鼠肝功能、血清细胞因子和肝肠组织的影响

目的探讨Roseburia hominis对肝硬化大鼠肝功能、血清细胞因子及肝脏、肠道组织的影响。方法 30只体质量250～300 g的雄性大鼠,随机分为3组:RH组10只、正常对照组10只,模型对照组10只,正常对照组给予生理盐水腹腔注射,其余20只大鼠均用四氯化碳制备肝硬化大鼠模型。模型制备后,在处死大鼠之前15天开始,RH组大鼠给予R.hominis活菌菌液灌胃,模型对照组给予等量生理盐水灌胃,采集样本测定。观察肝功能及血清细胞因子;对肝脏和肠道组织行石蜡包埋、切片、苏木精和伊红染色,病理切片观察对比组织的炎症和损伤程度。结果 RH组大鼠肝功能显著好转,ALT、AST、TB与模型组对比均显著下降(t=2.633 1、2.701 2、2.581 4,P=0.011 5、0.008 9、0.013 3)。血清细胞因子的检测结果显示,与模型对照组相比,RH组大鼠IFN-γ和IL-10的水平均显著升高(t=2.256 2、2.001 2,P=0.025 8、0.041 6)。RH组大鼠肝脏、肠道组织病理结果较模型对照组明显好转。结论 R.hominis对肝硬化大鼠肝功能有改善作用,可减轻肝脏及肠道组织损伤,提高血清中IFN-γ和IL-10水平。     

Subcellular manifestations of the corrective effect of alpha-tocopherol on postischemic changes in the liver parenchyma of rats

The influence of an antioxidant alpha-tocopherol on the intracellular organization of hepatocytes has been studied in the postischemic period. The introduction of alpha-tocopherol (before the onset of 120-min rat liver ischemia) did not decrease the size of necrosis in the liver parenchyma, but stimulated the membrane hyperplasia of cytoplasmic organoids, predominantly in mitochondria.