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PubMed2006

[The synthesis, characterization and in situ intestinal absorption of different molecular weight scutellarin-PEG conjugates].

In this report, highly water soluble esters of scutellarin with different molecular weight polyethylene glycol (PEG) were synthesized in order to improve the bioavailability of scutellarin. The physicochemical properties, the stabilities under different conditions and the in situ intestinal absorption in rats of the conjugates were investigated. By PEG modification, the greatly increased water solubility and desirable partition coefficient of scutellarin were obtained. These compounds function as prodrugs i. e. breakdown occurred in a predictable fashion: the t1/2 of them in PBS buffer at pH7.4 was above 12 h (37 degrees C) in vitro, while in plasma a rapid breakdown was observed, with a t1/2 of about 1. 5-3 h. The stabilities of the prodrugs were improved according to the increase of the molecular weight of PEG, thus, PEGylated prodrugs with desirable rates of hydrolysis could be obtained by the use of variable molecular weight PEGs. The PEGylation could enhance the absorption of scutellarin in rat intestine, and the absorption of scutellarin and its PEG conjugates by intestine was mainly via passive transport, for when the concentration was raised, the uptake did not appear saturable, and the permeability coefficient kept at an equilibrium level. When the molecular weight of PEG increased from 200 to 1000 Da, the absorption of the conjugates decreased. In conclusion, by overall consideration of the yield, stability and absorption, the present authors estimate that the PEG molecular weight used for the PEGylation of scutellarin should be within the range of 400-1 000 Da.

Animals↗
PubMed1996

Intestinal absorption barriers and transport mechanisms, including secretory transport, for a cyclic peptide, fibrinogen antagonist.

PURPOSE: The intestinal absorption of DMP 728, a cyclic peptide fibrinogen antagonist, was examined with the goals of identifying the cause(s) of its low oral bioavailability and understanding the mechanisms of its intestinal transport. METHODS: In vitro partitioning, metabolism, and permeation through rat intestinal segments were evaluated. RESULTS: DMP 728 had low lipophilicity and low intestinal permeation rates relative to model compounds. In addition, DMP 728 in vitro intestinal permeation in the secretory direction greatly exceeded transport in the absorptive direction. The secretory transport was saturable, glucose-dependent, and was inhibited by verapamil and by a monoclonal antibody to P-glycoprotein. DMP 728 likewise inhibited the secondary transport of verapamil. Mucosal-to-serosal permeation rates increased in going from the proximal to distal intestinal sites, but were lower than serosal-to-mucosal permeation rates for each site. CONCLUSIONS: Net secretory transport and low lipophilicity are the major barriers to absorption of DMP 728.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[Coupling of protease activity and sodium loading with intestinal absorption of amino acids].

Membrane-bound serine proteases to play a certain role in activation of sodium transport in epithelial cells. To were found explain the protease activity and sodium-dependent L-tryptophan transport across chicken small intestine interaction, four experiments were conducted. One hundred chicks were fed diets that contained 0; 0.3; 3 or 6% of supplemental NaCl and were given distillated water ad libitum. Signs of salt toxicity observed were as follows: a decreased body weight, increased heart and kidney weights, formation of secondary lysosomes in enterocytes and lymphocytes. Such chickens were in the state of negative nitrogen balance. Intestinal absorption of L-tryptophan correlated with mucosal protease activity during increased dietary sodium chloride intake. Recent in vitro and in vivo experiments indicate that enterocyte proteases may be of critical importance in activation of sodium-dependent intestinal transporters for L-tryptophan.

Animals↗
PubMed1985

Effect of bicarbonate feeding on intestinal absorption of calcium and vitamin D metabolism in rats.

The effect of bicarbonate (NaHCO3) feeding on intestinal absorption of calcium and phosphorus and vitamin D metabolism was investigated. Gut sac uptake of 45Ca and [32P]phosphate in vitro, as well as the plasma level of vitamin D metabolites, was determined in rats fed with NaHCO3 for 9 days and their pair-fed controls. Duodenal uptake of 45Ca and [32P]phosphate by alkalotic rats was less than duodenal uptake by controls. 1,25(OH)2D plasma level was much higher in alkalotic rats than in their controls, and 25(OH)D slightly higher than in controls. These data suggest that NaHCO3 feeding causes a substantial increase in 1,25(OH)2D plasma level, but interferes with calcium and phosphorus absorption in the duodenum.

24,25-Dihydroxyvitamin D 3↗
PubMed1968

Quantitative aspects of the intestinal absorption and metabolism of cholesterol and beta-sitosterol in the rat.

The quantitative aspects of intestinal absorption and metabolism of cholesterol and -sitosterol have been studied in the rat after a single feeding of radioactive sterols. When increasing amounts of cholesterol were fed in a constant amount of triolein, the percentage absorbed decreased only gradually and the total amounts absorbed increased to a maximum. Solubility in the fat component fed is one limiting factor in the absorption of cholesterol. At the lowest dose fed, only about 50% of dietary cholesterol was absorbed even though increasing the amount fed led to a 10- to 15-fold increase in total absorption. Sitosterol, when fed in triolein, was absorbed in amounts only one-tenth of the corresponding dose of cholesterol. Intestinal transit studies indicate that the distinction between sitosterol and cholesterol, when fed together, took place during the process of uptake into the intestinal mucosa. Once taken up by the intestinal mucosal cells, cholesterol and sitosterol did not differ in their subsequent rate of transit out of the mucosal cell. Feeding sitosterol with cholesterol seems to have the same effect on cholesterol absorption as feeding the same additional dose of cholesterol, the difference being that sitosterol is taken up by the intestinal wall in amounts only one-tenth to one-fifth of that of cholesterol. The rapid and complete absorption of the triglyceride fat and the subsequent transit of the intestinal content to the large intestine are most probably important factors in the determination of the extent of absorption of nonglyceride fat. The mechanism behind the difference in extent of absorption of the closely related sterols is not explained.

Animals↗
PubMed1987

Selenium-mercury interaction during intestinal absorption of 75Se compounds in chicks.

The effects of inorganic (HgCl2) and organic (CH3HgCl) mercury on the intestinal absorption of Se compounds [Na2(75)SeO3, Na2(75)SeO4, L-[75Se]methionine ([75Se]Met)] were determined in 3-wk-old White Leghorn cockerels by the in vivo ligated duodenal loop procedure. The intraduodenal dose contained 0.05 microCi 75Se, 0.01 mM Se, 150 mM NaCl and 0-1.0 mM Hg. In the presence of 1 mM inorganic Hg in the intraduodenal dose, the absorption of the inorganic 75Se compounds was only about 65% of that in the control group, whereas only a slight inhibitory effect on [75Se]Met absorption was observed. Methylmercury had no effect on [75Se]selenite absorption. Precipitation of the 75Se-selenite in the intestinal lumen partly explained the direct interaction between inorganic Hg and Se compounds. Absorption of [75Se]Met and [75Se]selenite was also determined in chicks fed after hatching a purified diet supplemented with varying amounts of Hg (0-500 mg/kg) and Se (0-4 mg/kg). Dietary Hg significantly reduced the transfer of [75Se]selenite to body by enhancing the accumulation of the isotope in the intestinal tissue. Dietary Hg did not affect the absorption of [75Se]Met, but altered the whole-body distribution of this Se compound. Because interaction between Se and Hg was observed mainly between the inorganic compounds and with use of a manyfold excess of Hg over Se, the data suggest that intestinal interaction between these metals is not of great nutritional importance.

Animals↗
PubMed1989

Effect of calcium and magnesium ions on the intestinal absorption of oleic acid in vitro.

The effect of Ca++ and Mg++ upon intestinal absorption of oleic acid was investigated using two in vitro models: rat isolated jejunal loops at 30 degrees C and 37 degrees C and mouse jejunal explants at 37 degrees C. At 30 degrees C or at 37 degrees C, Ca++ significantly increased 14C oleic acid uptake by rat isolated jejunal loops or mouse jejunal explants; at 37 degrees C, Ca++ significantly enhanced lipid exocytosis in rat intestinal loops but not in mouse jejunal explants; in both models, in the presence of Ca++ and at 37 degrees C, Mg++ significantly improved the esterification of oleic acid phospholipids and triacylglycerols, as shown by the increase in triacyglycerol synthesis in rat isolated intestinal loops or by the increase in triacylglycerols recovered from the incubation media of mouse jejunal explants; experiments carried out with rat isolated jejunal loops highlighted the determinant role of temperature in oleic acid absorption processes. The present work shows that the simultaneous presence of Ca++ and Mg++ did not impede oleic acid absorption processes but, on the contrary, enhanced them.

Animals↗
PubMed1995

Effect of chronic ethanol administration and dietary protein regimens on intestinal absorption of macromolecules in rats.

The effect of feeding ethanol daily for 40 days has been studied on intestinal absorption of bovine serum albumin (BSA) and gamma-globulin (IgG) in rats fed a low (8%) protein (LP) or a high (30%) protein (HP) diet. Feeding the LP diet enhanced the tissue uptake of BSA (p < 0.05) and absorption of BSA and IgG into serum (p < 0.001) as compared with controls. Feeding the HP diet also augmented the uptake of IgG (p < 0.001) by the intestinal tissue and significantly enhanced serum levels of BSA and IgG. Ethanol feeding to rats for 40 days enhanced the uptake of BSA and IgG (24-84%) and their absorption into serum (p < 0.001) as compared with the controls. Ethanol administration to rats fed LP or HP diets did not alter the uptake of these proteins as compared with their respective controls. Luminal degradation of BSA and IgG was higher in ethanol-administered (48-50% and 36-39%, respectively) and LP-fed rats (50 and 38%, respectively). It was reduced by 17-21% in HP-fed rats as compared with the control group. This indicated that the observed increase in protein absorption is not related to the luminal degradation of the proteins under these conditions. These findings suggest that the absorption of macromolecules from intestine in response to ethanol feeding is influenced by the dietary status of the animals.

Animals↗
PubMed2004

Role of anion exchange transporter PAT1 (SLC26A6) in intestinal absorption of organic anions.

Mouse PAT1 (putative anion transporter, CEFX, slc26a6), an orthologue of human SLC26A6, was recently identified at the intestinal brush-border membrane and shown to transport organic anions such as formate and oxalate, as well as inorganic ions. In this study, we conducted functional characterization of the uptake of formate by HEK293 cells transfected with PAT1. The uptake of formate by PAT1 was increased in the presence of an outwardly-directed Cl gradient, whereas Na had no effect, and the uptake was independent of pH. The Km of PAT1 for formate was 3.75 mM. Various organic acids exhibited a cis-inhibitory effect on the uptake of formate by PAT1. Furthermore, the uptake was increased by preloading with -lactate, nicotinate, valproate and short-and medium-chain fatty acids, showing a trans-stimulatory effect. Thus, it was suggested that PAT1 transports organic acids as well as inorganic anions, demonstrating that it is involved in the intestinal absorption of anionic organic weak acids in the small intestine.

Amino Acid Transport Systems↗
PubMed1979

Influence of luminal Na+ on the intestinal absorption of sugars in vivo.

The effect of substituting Na+ with Tris, Li+, K+ or mannitol on the intestinal absorption of sugars, in successive periods of 1 minute duration, has been studied in rat and hamster in vivo. The absorption of 2 mM D-glucose, D-galactose, 3-0-methyl-D-glucose and D-fructose is clearly inhibited in the absence of Na+, up to 70-80%, and returns to its normal value of restoring Na+. The degree of inhibition varies with the sugar, increases on lowering Na+ concentration, reaches maximum values with mannitol as substituent, and minimum with Tris, D-arabinose absorption is not affected by Na+. These results prove once more how important Na+ is in sugar intestinal transport in vivo, while they reveal additional influences of the different substituents on the transport system.

Animals↗
PubMed1984

Intestinal absorption of thiamin in man compared with folate and pyridoxal and its subsequent urinary excretion.

off intestinal absorption of thiamin was compared with that of folate and pyridoxal in six healthy volunteers using an oral dose of each vitamin equivalent to ten times the recommended daily allowance. Folate and pyridoxal were rapidly absorbed and following the oral dose, serum concentrations rose from a mean basal level of 10.9 micrograms/liter and 17.5 micrograms/liter to 174.8 micrograms/liter and 315.2 micrograms/liter respectively--an increases of 1,500% for folate and 1,701% for pyridoxal. The mean serum level of thiamin rose only marginally from 5.1 micrograms/liter to 7.2 micrograms/liter, an increase of 42%. One hour following the oral test dose of thiamin, the vitamin was actively excreted in the urine of all volunteers, with a mean creatinine/thiamin renal clearance ratio of 2.4. Active excretion continued for up to six hours. In contrast, folate was only actively cleared for a short period in two volunteers. Thiamin absorption appeared to be controlled and limited, and modest increases in the serum concentration were accompanied by active renal clearance.

Administration, Oral↗
PubMed1985

[Experimental study on intestinal absorption of elemental diet].

An isolated intestinal segment separated from the flow of digestive fluid was made according to the method of Thiry Vella in the jejunum, ileum and large intestine of mongrel adult dogs in order to examine absorption of elemental diet at each intestinal segment. The same experiment was undertaken in a segment in the irradiated jejunum prepared as a model of disturbed intestine. Amino acids were adequately absorbed at the segments in the jejunum and ileum, and the absorbing pattern of each free amino acid at the two segments was almost the same. Nutritional components of the elemental diet were also absorbed adequately at the segment in the large intestine. Each intestinal segment showed specificity in absorbing electrolytes. There was no difference in absorption of nutritional components between the segments in the irradiated jejunum and the normal intestine, but absorption of electrolytes was affected by irradiation.

Amino Acids↗
PubMed2004

Interaction of cholesterol with sphingosine: physicochemical characterization and impact on intestinal absorption.

Molecular associations between sphingomyelin and cholesterol provide a molecular basis for the colocalization of these lipids in plasma membrane microdomains (lipid rafts) and for the inhibitory effect of sphingomyelin on the intestinal absorption of cholesterol. Using surface pressure measurements at the air-water interface, we showed that sphingosine, the common sphingoid backbone of most sphingolipids, formed condensed lipid complexes with cholesterol. Structure-activity relationship studies with long-chain analogs of sphingosine, together with molecular mechanics simulations, were consistent with a specific interaction between sphingosine and the alpha face of cholesterol. The uptake of micellar cholesterol and the effect of sphingosine on cholesterol absorption were studied with two human model intestinal epithelial cell lines, Caco-2 and HT-29-D4. Real-time PCR quantifications of the putative cholesterol transporter Niemann-Pick C1 like 1 (NPC1L1) mRNA revealed that, in these cell lines, the activity of cholesterol transport correlated with the level of NPC1L1 expression. In both cell lines, sphingosine induced a dose-dependent decrease of cholesterol absorption. Yet the effect of sphingosine was more dramatic in Caco-2 cells, which also displayed the highest expression of NPC1L1 mRNA. Altogether, these data suggested that sphingosine interacts specifically with cholesterol and inhibits the intestinal NPC1L1-dependent transport of micellar cholesterol.

Binding Sites↗
PubMed1983

Intestinal absorption of dinitrophenyl-lysine and effect of immunization with dinitrophenylated bovine serum albumin.

The intestinal absorption of dinitrophenyl-lysine (DNP-lys) was studied with a special interest on the role of the immune system in the absorption of small molecules which are recognized as nonself. [3H]-DNP-lys was rapidly absorbed by ligated intestinal loops in situ via a saturable and unique route. When [3H]-DNP-lys was preincubated with the immune serum obtained from rats immunized with dinitrophenylated bovine serum albumin (DNP-BSA), the [3H]-DNP-lys absorption was depressed. The absorption of [3H]-DNP-lys in DNP-BSA-immunized rats was depressed compared to the control. The results obtained suggest that the immune system play a role in avoiding the absorption of small molecules with antigenicity.

Animals↗
PubMed1991

Intestinal absorption kinetics of a series of aminopenicillins and azidocillin. A comparative study in the rat.

Intestinal absorption rate constants of amoxicillin, ampicillin, epicillin, cyclacillin and azidocillin, by means of a static in situ intestinal perfusion method has been estimated. Luminal remaining antibiotic concentrations were determined using a standard microbiological technique. In order to establish statistically better absorption kinetics, five dose levels were used, ranging from 10 to 1000 micrograms/ml, and first order, Michaelis-Menten and combined first-order and Michaelis-Menten differential model equations were fitted to experimental data found for each antibiotic. According to the AIC test, the best equation for absorption kinetics was selected. Amoxicillin and ampicillin absorption mechanisms were better described by combined kinetics, while for cyclacillin and epicillin the most probable kinetics was that of Michaelis-Menten. For azidocillin, the only non-aminopenicillin component of this series, first order kinetics should be statistically selected.

Amoxicillin↗