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PubMed1984

Intestinal absorption of vitamin E in low birth weight infants.

Intestinal absorption of dl-alpha-tocopheryl acetate was studied in low birth weight infants. Vitamin E was given from the first day of life, either as a water-soluble (Ephynal) or as a lipid-soluble preparation (E-vitamin). Serum-alpha-tocopherol concentrations were determined before treatment and on days three and seven. Treatment with both vitamin E preparations increased serum-alpha-tocopherol on day three and seven. The mean serum-alpha-tocopherol +/- SD on day seven were 41.4 +/- 10.7 mumol/l for the Ephynal group and 26.7 +/- 12.5 mumol/l for the E-vitamin group, this difference being statistically significant (p less than 0.025). Oral feeding seems to influence the absorption of tocopherol from E-vitamin, as the infants with the highest serum-alpha-tocopherol concentrations were those with the highest oral/total feeding ratios. In infants with birth weight less than 1 000 g treatment with 25 mg Ephynal/day was found to increase serum-alpha-tocopherol on day seven to 46.9 +/- 12.3 mumol/l (mean +/- SD). This concentration is comparable to those reported by others using higher doses of oral vitamin E.

Humans↗
PubMed1987

Effect of allopurinol on the intestinal absorption of 6-mercaptopurine in rats.

The effect of allopurinol, a xanthine oxidase inhibitor, on the intestinal absorption characteristics of 6-mercaptopurine was investigated by in situ and in vitro absorption techniques in rats. In the in situ experiment, the percent disappearance of 6-mercaptopurine from the lumen showed a dependency on initial drug concentration. Most of the 6-mercaptopurine that was lost from the lumen appeared as its metabolite, 6-thiouric acid, in the lumen. Dose-dependency of 6-mercaptopurine disappearance from the lumen and the biotransformation of drug to 6-thiouric acid were not observed in the presence of allopurinol. The in vitro data supported the results of the in situ experiment. In addition, allopurinol increased the serosal transfer in vitro and the mesenteric appearance of 6-mercaptopurine in situ by inhibiting the biotransformation to 6-thiouric acid. These results suggested that the type of absorption characteristics observed with 6-mercaptopurine was due to its metabolism by xanthine oxidase in the intestine.

Allopurinol↗
PubMed1982

Influence of temperature of the perfusion solution on the kinetics of intestinal absorption of glucose in rats.

The kinetics of glucose intestinal absorption by rat jejunum at different solution temperatures, under single pass perfusion, has been studied in vivo. The non-passive component (active transport) has been measured as difference between control absorption and that in the presence of 5 X 10(-4) M phloridzin. Results at 37 degrees and 39 degrees C did not significantly differ, but at 32 degrees C a clear drop in total absorption, non-passive and passive components was observed. As temperature increases from 32 degrees to 37 degrees C the apparent value of Km for glucose transport decreases (from 21.2 mM to 13.1 mM), whilst the Vmax does not change, and the apparent mass-transfer coefficient for the passive component slightly increases. The results are discussed taking in consideration the effect of temperature on the diffusion across the unstirred water layers and on the active transport processes.

Animals↗
PubMed1992

Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats.

The intestinal absorption and in vivo kinetics of (6S)-[3H]-5-methyl-tetrahydrofolate (5-methyl-H4folate), (6S)-[3H]-5-formyl-H4folate and [3H]folic acid were investigated to determine whether inherent differences exist in the overall bioavailability of these folates in rats. Adult rats (n = 9 per group) were given an intragastric dose of the appropriate folate (50 pmol/100 g body wt) in 50 mmol/L ascorbate (pH 7). Each compound underwent nearly complete absorption within 8 h, and there was no significant difference in the excretion kinetics in relation to the form of folate administered. A biphasic pattern of excretion was observed over the following 8 d. Both urine and feces were important excretory routes. The rapid phase of total isotopic excretion (urinary and fecal) exhibited a half time (t1/2) of 0.11-0.12 d, whereas the t1/2 of the slower phase was 13.4-15.9 d. Isotopic distributions and the pattern of labeled folates in urine and tissues were similar regardless of the form administered. These results indicate that the bioavailability of orally administered folic acid, 5-methyl-H4folate and 5-formyl-H4folate is equivalent in rats under the conditions of this study.

Animals↗
PubMed1988

Influence of the disaccharide lactitol on intestinal absorption and body retention of calcium in rats.

Various sugars are known to stimulate intestinal calcium absorption by a mechanism that is still poorly understood. One of those, the disaccharide 4-gal-actosyl-sorbitol (lactitol), is only metabolized in the large intestine, where it is converted into acidic residues. We investigated the effect of this compound on net intestinal absorption and body retention of calcium in rats. Because dietary calcium is in a poorly absorbable form when it reaches the large intestine, attempts were made to modify the absorption of calcium present in the large intestine contents by administering lactitol. Net intestinal absorption and body retention of calcium were significantly increased by 2.5 g lactitol/(kg b.w.d) given by a gavage over a 7-d period. This was associated with a lower pH and a better availability to absorptive systems of calcium present in the large intestine contents. The results indicate that in rats lactitol given chronically increases net intestinal absorption of calcium with a subsequently more positive calcium balance.

Animals↗
PubMed1980

Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog.

1. Pentagastrin (1, 10 micrograms/min) was infused I.V. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H2O and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H2O were used to determine the unidirectional Na and H2O fluxes from saline perfused through the ileal lumen and the clearances of 3H2O were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H2O was reduced by 10 micrograms/min pentagastrin due primarily to significant increases in the secretory flux of Na and decreases in the absorptive flux of H2O in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H2O. The relationships between the secretory fluxes of Na and H2O and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption.

Animals↗
PubMed1988

The mechanisms of intestinal absorption of the carcinogen MNNG (N-methyl-N'-nitro-N-nitrosoguanidine).

We studied the characteristics and mechanisms of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) intestinal absorption and the interaction between bile acids and fatty acids and MNNG absorption rate in vivo in male Sprague-Dawley rats. We perfused a segment of the proximal small bowel with a physiological solution containing MNNG to assess its basic kinetics and the influence of some physiological and dietary factors on carcinogen absorption. We found that MNNG was absorbed by simple passive diffusion. Transport of MNNG was the highest at pH 6.0. The addition of the bile salt, taurocholate by itself, greatly increased MNNG absorption, while the addition of the long-chain unsaturated fatty acids, oleic and linoleic, decreased the rate of absorption of MNNG. The phospholipid lecithin addition to the perfusate did not change the rate of MNNG absorption. Induction of dietary vitamin A deficiency (serum vitamin A level decreased from 40.9 to 13.7 micrograms/dl) did not change the absorption rate of MNNG. These studies demonstrate that bile acids, dietary fatty acids, and the pH of the intestinal content can modify the rate of absorption of this carcinogen by the small intestine. Since initial intestinal absorption determines serum levels and subsequent reabsorption and enterohepatic cycling determines long-term lumenal levels, serum levels, and total body content, factors which modify the rate of intestinal absorption of MNNG could also modify its carcinogenicity.

Animals↗
PubMed1991

A model of human small intestinal absorptive cells. 1. Transport barrier.

The Caco-2 cell culture model of human small intestinal absorptive cells was used to investigate transepithelial transport. Transport of permeability markers such as mannitol demonstrated that Caco-2 monolayers became less permeable with increasing age in culture. Cells were routinely used for transport studies between day 18 and day 32. A transport index was determined for each compound by calculating the ratio of transport of the molecules under investigation to transport of an internal standard such as the permeability marker mannitol. Comparison of transport rates at 4 and 37 degrees C was a simple approach for differentiating primary transport mechanisms (passive paracellular, passive transcellular, or transporter-mediated) but must be coupled with additional experimental manipulations for definitive determination of transport pathways. Compounds predicted to undergo predominantly paracellular transport (mannitol, FITC, PEG-900, and PEG-4000), transporter-mediated transcellular transport (glucose, biotin, spermidine, or alanine), or lipophilic transcellular transport (alprenolol, propranolol, clonidine, or diazepam) showed differential effects of temperature on rates of transport as well as the transport index.

Biological Transport↗
PubMed1986

Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity.

Intestinal absorptive cells may modulate both the structure and function of occluding junctions by a cytoskeleton dependent mechanism (Madara, J. L., 1983, J. Cell Biol., 97:125-136). To further examine the putative relationship between absorptive cell occluding junctions and the cytoskeleton, we assessed the effects of cytochalasin D (CD) on occluding junction function and structure in guinea pig ileum using ultrastructural and Ussing chamber techniques. Maximal decrements in transepithelial resistance and junctional charge selectivity were obtained with 10 micrograms/ml CD and the dose-response curves for these two functional parameters were highly similar. Analysis of simultaneous flux studies of sodium and the nonabsorbable extracellular tracer mannitol suggested that CD opened a transjunctional shunt and that this shunt could fully account for the increase in sodium permeability and thus the decrease in resistance. Structural studies including electron microscopy of detergent-extracted cytoskeletal preparations revealed that 10 micrograms/ml CD produced condensation of filamentous elements of the peri-junctional contractile ring and that this was associated with brush border contraction as assessed by scanning electron microscopy. Quantitative freeze-fracture studies revealed marked aberrations in absorptive cell occluding junction structure including diminished strand number, reduced strand-strand cross-linking, and failure of strands to impede the movement of intramembrane particles across them. In aggregate these studies show that CD-induced perturbation of the absorptive cell cytoskeleton results in production of a transepithelial shunt which is fully explained by a defect in the transjunctional pathway. Furthermore, substantial structural abnormalities in occluding junction structure accompany this response. Lastly, the abnormalities in occluding junction structure and function coincide with structural changes in and contraction of the peri-junctional actin-myosin ring. These data suggest that a functionally relevant association may exist between the cytoskeleton and the occluding junction of absorptive cells. We speculate that such an association may serve as a mechanism by which absorptive cells regulate paracellular transport.

Animals↗
PubMed1999

Elucidation of intestinal absorption of D,L-amino acid enantiomers and aging in rats.

At the present time, the origin of protein bound D-amino acid (AA) has been fairly well elucidated, but that of free D-AA is still not well understood. To gain greater understanding of this, intestinal absorption in rats of free D,L-AA enantiomers (arginine, alanine and aspartic acid as models for basic, neutral and acidic AAs, respectively, in this study) and the relationship between age and absorption were investigated. The degree of rat intestinal absorption of free D,L-AAs was evaluated using apparent membrane permeability coefficients (Papp) which were obtained from an in situ intestinal single-pass perfusion method with Krebs-Ringer bicarbonate buffer (pH 7.4) solution containing D,L-AA enantiomers. Determinations of D,L-AA enantiomers in perfusion (in- and outflow) solutions were carried out by the in-capillary derivatization high-performance capillary electrophoretic methods (ICD-HPCE methods) that were previously developed by our group. Collectively, our observations suggest: (1) that the Papp of L-AA is higher than that of the D-isomer; (2) that D-AA can be absorbed as well as L-AA using a sodium ion-dependent transporter that is located on the brush border membrane of rat intestinal epithelial cells; (3) that Papp reached a maximum at 8 weeks of age, but were measured at decreased amounts at 52 and 104 weeks of age. These results suggest that free D-AA in a mammalian body originates from 'exogenous sources'.

Aging↗
PubMed1993

Comparison of intestinal absorption of cholesterol with different plant sterols in man.

Intestinal absorption of cholesterol, campesterol, campestanol, stigmasterol and sitosterol were measured in 10 healthy subjects by an intestinal perfusion technique over a 50 cm segment of the upper jejunum using sitostanol as non-absorbable marker. Cholesterol absorption was highest and averaged 33%., whereas the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%. Higher absorption rates were found for campesterol (9.6%). Campestanol, the 5 alpha saturated derivative of campesterol, showed the highest absorption rate (12.5%) of all plant sterols. A positive correlation between the absorption rate of cholesterol and campesterol was established. In addition, there was a negative correlation between the ratio of sitosterol to cholesterol and the mass of cholesterol absorption. These results are in agreement with previous observations in animal studies, namely, that increasing the length of the side-chain of cholesterol decreases the absorbability of the sterol. Surprisingly, campestanol, the 5 alpha saturated derivate of campesterol, was shown to have higher absorbability compared with its unsaturated compound. This finding is in contrast to previous assumptions, that hydrogenisation of the nucleus double bond of a sterol causes a decrease of absorbability, as has been demonstrated for cholesterol/cholestanol and sitosterol/sitostanol.

Cholesterol↗
PubMed1982

Effect of mercuric chloride on the intestinal absorption of an amino acid, glycine, in the freshwater murrel, Channa punctatus.

The effect of five concentrations of mercuric chloride (10 mM, 1 mM, 0.1 mM, 0.01 mM, 0.001 mM) on the rate of absorption of the amino acid glycine by the intestine of the freshwater murrel Channa punctatus has been studied. Intestinal absorption of glycine was also studied in fish exposed to a sublethal concentration (3 micrograms/l) of mercuric chloride for 15 and 30 days. The results revealed that all the five concentrations of mercuric chloride reduced the rate of absorption of glycine by the intestine. Maximum decrease was recorded with 10 mM of mercuric chloride in the instilled medium. The reduction in glycine transport was insignificant with 0.01 and 0.001 mM of mercuric chloride. In fish exposed to mercuric chloride by bath also, decrease in the rate of absorption of glycine was noted but it was significant only after 30 days of exposure.

Animals↗
PubMed1995

In situ intestinal absorption of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in guinea pigs.

The intestinal absorption efficacy of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), which has been recently synthesized and characterized as a stable ascorbate (AsA), was determined in guinea pigs by the perfusion technique. Perfusion of AA-2G in isotonic phosphate buffer to the small intestine resulted in a decrease of AA-2G accompanied by an increase of AsA in the perfusate. The results showed that intact AA-2G was not detected in the plasma of the portal vein of guinea pigs at 2 h after perfusion. The disappearance of AA-2G from perfusate was completely inhibited by the addition of castanospermine, a specific alpha-glucosidase inhibitor, or by carbohydrates such as maltose. These results indicate that ascorbic acid released from AA-2G by alpha-glucosidase on the brush border membrane is effectively taken up across the intestinal ascorbate transport channels, into a serosal site, whereas AA-2G permeation was poor via the passive transport system.

Animals↗
PubMed1997

Intestinal absorption and enterohepatic cycling of biliary iron originating from plasma non-transferrin-bound iron in rats.

In iron overload, non-transferrin-bound iron (NTBI) is found in plasma and is rapidly removed by hepatocytes. Some of this NTBI is excreted into bile. Biliary excretion of NTBI, in the form of an iron-deferiprone chelate, is greatly increased by deferiprone, an iron chelator. The aim of this study was to test whether biliary iron as such or as an iron-deferiprone chelate (both originating from plasma NTBI) is absorbed from the intestine and re-secreted into bile. In healthy biliary fistula (donor) rats, biliary 55Fe originating from plasma NTBI was obtained by injecting Fe citrate (to saturate transferrin) followed by 55Fe. This biliary 55Fe was infused into the duodenum of (recipient) rats whose transferrin was saturated or unsaturated. Similar experiments were performed using iron-overloaded (donor) rats given deferiprone, followed by infusion of the biliary 55Fe-deferiprone chelate into iron-overloaded (recipient) rats. The results show that in healthy (recipient) rats, duodenal infusion of 55Fe from NTBI was followed by increased plasma 55Fe when transferrin was unsaturated, or by biliary excretion of 55Fe when transferrin was saturated, indicating intestinal absorption of 55Fe. In iron-overloaded rats, neither plasma nor bile became radioactive, indicating no intestinal absorption of iron from the deferiprone chelate. We conclude that biliary iron, originating from NTBI, is absorbed from the intestine, and undergoes enterohepatic circulation if transferrin is saturated. In iron-overloaded rats, biliary iron originating from plasma NTBI and present as an iron-deferiprone chelate in bile is not absorbed.

Animals↗
PubMed1986

Intestinal absorption of tetramethylammonium and its derivatives in rats.

The intestinal absorption of tetramethylammonium (TMA) and its derivatives from rat jejunum has been investigated with an in situ loop method and an in vitro everted sac method. At a low concentration, TMA was absorbed rapidly from the in situ intestinal lumen without being metabolized in the tissue and the rate of absorption was dependent upon the concentration used. The profile of TMA absorption included two processes, i.e. saturable and non-saturable. The absorption of TMA was inhibited competitively by analogs that have a N-trimethyl group in their structure. Among them, choline showed the strongest inhibition to TMA absorption. The inhibitory potency of these analogs was related to their chemical structure. Although TMA was not transported into the intracellular fluid of the everted intestine against a concentration gradient, the tissue accumulation of TMA was inhibited by 2,4-dinitrophenol (2,4-DNP), a metabolic inhibitor, and was highly dependent upon the incubation temperature. These findings demonstrate that TMA is absorbed through the rat small intestine by a carrier mediated transport system. An apparent Kt of 0.73 mM and a maximum V of 11.5 nmol/g tissue wet wt/min were determined by an in situ loop method. It was also suggested that the endogenous quaternary ammonium compound, choline, might be absorbed by the same carrier system.

2,4-Dinitrophenol↗
PubMed1982

The Golgi apparatus of rat small intestinal absorptive cells. I. Morphology and cytochemical staining pattern in proximal and distal small intestinal regions.

Comparative studies on the Golgi apparatus of rat small intestinal absorptive cells from duodenal, jejunal and ileal segments showed that the characteristic polarity of Golgi stacks is apparent along the entire small intestine; dilated cisternae containing lipoprotein particles are preferably localized at one Golgi side (cis face); narrow, regular cisternae predominate at the other side (trans face). Osmium deposits after prolonged osmification are restricted to cis Golgi cisternae. Pronounced differences between proximal and distal small intestinal regions exist in the cytochemical staining pattern of Golgi stacks after localization of thiamine pyrophosphatase, inosine diphosphatase and acid phosphatase. In duodenal and proximal jejunal absorptive cells demonstration of thiamine pyrophosphatase and inosine diphosphatase causes heavy deposits of reaction product over all Golgi cisternae; in the distal jejunum and in the ileum only 1-3 cisternae at the trans Golgi side are reactive. Similarly, the number of acid phosphatase-positive cisternae decreases from proximal to more distal small intestinal regions. Thiamine pyrophosphate, nucleoside diphosphatase and acid phosphatase are assumed to be active in glycosylation being involved in the removal of uridine diphosphate and other nucleoside phosphates (Tartakoff, 1980; Farquhar and Palade, 1981; Roth and Berger, 1982). Accordingly, the differences in the Golgi apparatus staining pattern after localization of these enzymes between proximal and distal small intestinal segments may reflect regional differences in the glycosylation of apoproteins in lipoprotein particles and in the kinetics of glycosylated plasma membrane and lysosomal constituents.

Acid Anhydride Hydrolases↗
PubMed1999

Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption.

PURPOSE: Appropriate physicochemical parameters are desired for the prediction of passive intestinal drug absorption during lead compound selection and drug development. METHODS: Liposome distribution coefficients measured titrimetrically and solubility data at pH 6.8 were used to characterize 21 structurally diverse ionizable drugs covering a range from <5% to almost complete absorption. RESULTS: A sigmoidal relationship was found between the percentage of human passive intestinal absorption and a new absorption potential parameter calculated from liposome distribution data and the solubility-dose ratio. In contrast, the human absorption data did not correlate with an octanol-based absorption potential or partitioning data alone. Poor correlations were found between liposome and octanol partitioning of ionic species or nonionic bases indicating the profound differences of the partitioning systems. CONCLUSIONS: Liposome distribution coefficients of ionizable drugs derived by a pH-metric titration were successfully used to calculate a parameter that correlates with the percentage of passive intestinal absorption in humans. Profound differences between liposome and octanol partitioning were found for a highly diverse set of species. This titration technique may serve to generate liposome partitioning data for the selection and optimization of lead compounds and in drug development.

Humans↗
PubMed1987

Effect of vasoactive intestinal peptide, somatostatin, neurotensin, cholecystokinin octapeptide, and secretin on intestinal absorption of amino acid in rat.

The effects of vasoactive intestinal peptide (VIP), somatostatin (SRIF), neurotensin (NT), cholecystokinin octapeptide (CCK-8), and secretin (SEC) on the intestinal absorption of amino acid were investigated. Six groups of Wistar rats were studied: (1) controls; (2) VIP treated; (3) SRIF treated; (4) NT treated; (5) CCK-8 treated; (6) SEC treated. [3H]Leucine was given intraluminally through a cannula at the ligament of Treitz, a number of blood samples were obtained through a superior mesenteric vein catheter 1-60 min after administration of [3H]leucine, and the radioactivity of plasma was measured to evaluate the absorption of [3H]leucine. It was shown that VIP and SRIF significantly inhibited the absorption of [3H]leucine (by 59.1% and 38.7%, respectively), whereas NT, CCK-8, and SEC significantly enhanced absorption (by 44.2%, 49.6%, and 39.1%, respectively). Radioimmunoassays of VIP, SRIF, and NT showed that at least some of the hormones or peptides exerted their effects on absorption of leucine at or near their physiological concentrations.

Animals↗