[Intestinal absorption: its study by continuous intestinal perfusion. Critical review].
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Carbohydrate Metabolism↗
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Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice.
Carboxyl ester lipase (CEL; EC 3.1.1.13) hydrolyzes cholesteryl esters and retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate cholesterol and retinol from their esters prior to absorption in the intestine. CEL is also a major lipase in the breast milk of many mammals, including humans and mice, and is thought to participate in the processing of triglycerides to provide energy for growth and development while the pancreas of the neonate matures. Other suggested roles for CEL include the direct facilitation of the intestinal absorption of free cholesterol and the modification of plasma lipoproteins. Mice with different CEL genotypes [wild type (WT), knockout (CELKO), heterozygote] were generated to study the functions of CEL in a physiological system. Mice grew and developed normally, independent of the CEL genotype of the pup or nursing mother. Consistent with this was the normal absorption of triglyceride in CELKO mice. The absorption of free cholesterol was also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only about 50% of the cholesterol provided as cholesteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting that another enzyme besides CEL can hydrolyze dietary CE in mice. Surprisingly, CELKO and WT mice absorbed similar amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was required for absorption, implying that CEL was not the responsible enzyme. The changes in plasma lipid and lipoprotein levels to diets with increasing lipid content were similar in mice of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides.
Animals↗
Effect of magnesium on the intestinal absorption of calcium in man.
OBJECTIVE: In view of the widespread use of magnesium (Mg) as a nutritional supplement, we investigated whether Mg would affect the absorption of calcium (Ca) as the intestinal absorption sites for Mg and Ca differ. METHODS: The intestinal absorption of Ca, using 47CaCl2 as the tracer, and metabolic balances of Ca, phosphorus (P) and Mg were determined in five adult males under strictly controlled dietary conditions in control studies and during Mg supplementation. Mg was given as magnesium oxide (MgO) in 10 studies during two Ca intakes: five studies during a low Ca intake of 241 mg/day and five studies during a normal Ca intake of 812 mg/day. Dietary Mg intake ranged from 241 to 264 mg/day in control studies. During Mg supplementation, the total Mg intake ranged from 789 to 826 mg/day. RESULTS: There was no change of the intestinal Ca absorption during Mg supplementation during the two Ca intakes. The only change was the higher 1-hour 47Ca plasma level in the 47Ca absorption studies during the high Mg intake. Urinary Ca increased during Mg supplementation only during the low Ca intake, the Ca balance became more negative but this difference was not significant. There was also no change in Ca excretion or Ca balance during the high Mg intake at the normal Ca intake of 800 mg/day. P balance studies showed a slight decrease in urinary P and an increase in fecal P, but the P balances did not change. Mg balances were negative in control studies during the two Ca intakes. Supplemental Mg increased both urinary and fecal Mg excretion and the Mg balance became positive, but these differences were not significant. CONCLUSION: The increased Mg intake of 826 mg did not affect intestinal Ca absorption determined with tracer doses of 47Ca during Ca intakes of 241 and 812 mg/day.
Adult↗
Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments.
New data on the permeabilities of hydrophilic markers in two commonly used in vitro models, i.e., excised intestinal segments from the rat and monolayers of Caco-2 cells, are presented. The results are compared to human in vivo data. Two groups of hydrophilic marker molecules were tested: (1) monodisperse polyethylene glycols of molecular weights ranging from 194 to 502 g/mol and (2) a heterogeneous group of molecules consisting of urea, creatinine, erythritol, and mannitol (60-182 g/mol). The permeabilities of the marker molecules showed a nonlinear dependence on the molecular weight and decreased in the order rat ileum > rat colon > Caco-2 cells. Surprisingly, the polyethylene glycols permeated more easily than the other marker molecules, indicating that characteristics other than molecular weight, e.g., the flexibility of the structure, may also be important for permeation through the membrane. Comparisons with the published permeability profiles of polyethylene glycols in human intestinal segments in vivo (i.e., calculated permeability coefficients as a function of molecular weight) indicate that the human intestine is more permeable than the in vitro models. However, the permeability profiles of the corresponding segments in the human intestine and the in vitro models were comparable. Thus, good correlations were established between permeabilities of the human ileum and rat ileum and between those of human colon, rat colon, and the Caco-2 cells. We conclude that the paracellular absorption in humans can be studied mechanistically in these in vitro models.
Animals↗
Intestinal absorption of 1,25-dihydroxyvitamin D3 in the rat.
Intestinal absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] from in vivo jejunal sacs was studied in rats with thoracic duct and bile duct cannulas. In 6 h 86.5% of the administered 1,25(OH)2D3 was absorbed, but only 7.3% was recovered in thoracic duct lymph. Appearance in plasma of [3H]-1,25(OH)2D3 after intrajejunal administration was identical in rats with and without diverting lymph cannulas, indicating that the 1,25(OH)2D3 is absorbed almost entirely via portal blood. When 1,25(OH)2D3 was instilled into the jejunum in a fat suspension without bile salts rather than a mixed micellar solution, less was recovered in lymph, but total intestinal absorption was unchanged. High-pressure liquid chromatography of a lymph extract demonstrated that 1,25(OH)2D3 was present only as the unchanged secosteroid. In lymph, only 4.1% of the 1,25(OH)2D3 was in the chylomicrons, with the remainder bound to the plasma protein fraction of lymph. Treatment of rats with cycloheximide to block chylomicron synthesis did not decrease absorption of 1,25(OH)2D3. These results indicate that intestinal absorption of 1,25(OH)2D3 is effective and not very dependent on luminal bile salts. Almost all 1,25(OH)2D3 is released from the intestine directly into portal blood and does not require packaging in chylomicrons for transport into intestine lymph.
Animals↗
Interleukin-11 enhances small intestine absorptive function and mucosal mass after intestinal adaptation.
BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR. METHODS: Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM. RESULTS: IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d. CONCLUSIONS: In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.
Adaptation, Physiological↗
[Postoperative intestinal absorption in old age (author's transl)].
The function of intestinal absorption was analysed in elderly patients before and after cholecystectomy by the help of the modified D-xylose-absorption test. A characteristic dependence upon the age for the process of intestinal absorption was demonstrated in the elderly not only preoperatively but also postoperatively. The effective intestinal absorption of D-xylose normalized postoperative by in freshly operated older patients more slowly than in younger ones.
Aged↗
Intestinal absorption of cephalexin in diabetes mellitus model rats.
We investigated the intestinal absorption and pharmacokinetics of cephalexin, as well as the intestinal H+/oligopeptide transporter PEPT1 mRNA and protein levels in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum loop was significantly lower in streptozotocin-induced type 1 diabetic rats and higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa/fa (Zucker) rats, than in control rats. These results were speculated to be due to the enhancement of intestinal absorption of cephalexin in GK and Zucker rats. Intestinal PEPT1 mRNA levels were not significantly different between control and diabetic rats; however, the brush-border membrane vesicle PEPT1 protein levels were increased in GK and Zucker rats. After oral administration of cephalexin, plasma cephalexin concentrations and pharmacokinetic parameters, area under the concentration versus time curve from 0 to infinity, AUC(0-->infinity), and maximum plasma concentration, Cmax, in GK and Zucker rats were markedly higher than in control rats. From these findings, it is considered that intestinal absorption of drugs mediated by PEPT1 may be enhanced in hyperinsulinemic type 2 diabetes mellitus rats.
Animals↗
On the mechanism of human intestinal absorption.
In order to investigate whether the main step in intestinal absorption in humans is dominated by partition or by diffusion, we have transformed % human intestinal absorption into a first-order rate constant, and have regressed the latter, as logk, against our solvation parameters. The obtained regression coefficients are compared with those for diffusion and partition processes. The coefficients in the logk equation are completely different to those for water/solvent partitions, but are very similar to those for processes (not involving transport through membranes) in which diffusion is the major step. It is suggested that the main step in the absorption process is diffusion through a stagnant mucus layer, together with transfer across the mucusmid R:membrane interface. It is further shown that for strong Bronsted acids and bases, the rate constant for absorption of ionic species is close to that for absorption of the corresponding neutral species, so that to a first approximation the % intestinal absorption can be calculated from properties of the neutral species.
Biological Transport↗
[Prediction of human intestinal absorption from net polar atomic charges of drug molecules].
OBJECTIVE: To predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules. METHODS: The net atomic charges and the volumes of drug molecules were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations. RESULT: Both percent of human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules were well correlated with the sum of the net atomic charges of all hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges of hydrogen-bonding donors and the net negative atomic charges of hydrogen-bonding acceptors, the less were the percent human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules. CONCLUSION: Drug absorption in human intestines is closely related with its hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding potential have greater percent human intestinal absorption. The net polar atomic charges can be computed simply, so they can be used in high throughput screening of oral drugs.
Adrenergic beta-Antagonists↗
Nonabsorbable marker and single, random stool samples used for measuring intestinal absorption of macronutrients in infants and children.
To measure intestinal absorption by using a single, random stool sample, polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration, apparent intestinal absorption of macronutrients was estimated from a standard 3-d metabolic balance and compared with that estimated by using the ratio of PEG to macronutrients in a single random sample of feces. Correlation coefficients for this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat, respectively. Additionally, apparent intestinal absorptions estimated from two separate consecutive 3-d metabolic-balance studies were compared, showing correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate, and fat, respectively. The random sample-marker technique appears to be acceptable for measuring apparent absorption of macronutrients and is at least as accurate as a standard 3-d metabolic-balance study.
Child, Preschool↗
[Observations on the p-aminohippuric acid absorption coefficient method for study of intestinal absorption in man and in the rabbit].
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Animals↗
One-hour test for estimating intestinal absorption of calcium by using stable strontium as a marker.
Intestinal absorption of calcium is a relevant marker in a broad spectrum of diseases; however, its determination in clinical practice is difficult. Our aim was to design a simple test for this based on stable strontium (88Sr). The correlation between the intestinal absorption of simultaneously administered 45Ca and 88Sr was investigated in patients with various disorders of the bone and calcium metabolism. The area under the curve for the period 0-60 min after dosing (AUC0-60 in mmol.L-1.min), being a representative measure of intestinal absorption, showed a close correlation between both elements (r = 0.90, P < 0.001). Moreover, the measure of agreement in classifying the patients as low, intermediate, or high absorbers was high (kappa = 0.80). We conclude that a test based on measuring AUC0-60 of strontium is a fast and inexpensive way to obtain reliable information about the level of intestinal calcium absorption.
Adolescent↗
The effect of lactose on the intestinal absorption of calcium and zinc in the rat during maturation.
Lactose facilitates the intestinal absorption of several minerals and trace elements in postweanling rats. There is no information in the literature on the effect of lactose on the process of absorption in suckling rats. Because soy and elemental formulas are nonlactose-containing diets, the role of lactose in facilitating the intestinal absorption of minerals is of considerable nutritional importance. We studied therefore, the effect of water (control), lactose, sucrose, and glucose on the intestinal absorption and tissue uptake of calcium and zinc in the suckling (14-15 day old) and adolescent (42-43 day old) rats. Our results indicate that absorption of calcium and zinc was significantly greater in the suckling than in adolescent rats (P less than 0.01). Lactose enhanced significantly the absorption and tissue uptake of calcium and zinc in the adolescent rats compared to control and other sugars. In the suckling rats lactose had no effect on the intestinal absorption or tissue uptake of calcium and zinc compared to control and other sugars. The possible mechanism(s) responsible for our findings are discussed.
Age Factors↗
Intestinal absorption of peptides. Peptide uptake by small intestine of Rana pipiens.
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Animals↗
The effect of exercise associated with acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats.
The intestinal absorption of D-xylose was studied during acute poisoning of male Wistar rats receiving intragastrically potassium nitrate and sodium nitrite and small intestine perfusion with these compounds. The metabolic parameters, Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level, were assessed in the small intestine mucosa one hour after administration of these compounds. Exercise was demonstrated to reduce the intestinal absorption of D-xylose, to raise the level of lactic acid, and to increase the oxygen uptake by the small intestine mucosa, but caused no changes in the activity of Na+/K(+)-ATPase or alkaline phosphatase. Also, exercise failed to change the direction of the toxic effects of sodium nitrite but increased potassium nitrate toxicity as evidenced by reduced absorption of D-xylose from the intestine despite lack of changes of the enzymes Na+/K(+)-ATPase and alkaline phosphatase in the mucosa.
Alkaline Phosphatase↗
Passive and carrier-mediated intestinal absorption components of captopril.
The intestinal absorption mechanism of captopril was investigated in fasted rats using a single-pass perfusion method. Captopril and captopril disulfide were analyzed by HPLC. A modified boundary-layer solution was applied to determine the apparent intestinal wall permeabilities (Pw*). The results indicated that captopril is very permeable in the small intestine but not in the colon, and the permeability in the small intestine is both pH and concentration dependent. The estimated parameters for the carrier are: Km*, 6 mM; Jmax*, 12 mM; and Pc*, 2. There is also a significant passive component to captopril absorption in the small intestine. Furthermore, the intestinal permeability of captopril was significantly decreased by the withdrawal of sodium from the perfusate (3 times), and the addition of 85 mM of gly-gly (2.5 times), 15 mM of gly-pro (4 times), dipeptide mixture (4.5 times), 0.5 mM of 2,4-dinitrophenol (4 times), and 10 mM of cephradine (6 times). This is the first demonstration that an angiotensin converting enzyme (ACE) inhibitor is at least in part transported by a carrier-mediated process in the intestine via the peptide carrier system. In addition, the results showed that the peptide carrier system can transport a substrate without a "N" terminal nitrogen atom.
Animals↗
A 'rule of unity' for human intestinal absorption.
The ability to predict the passive intestinal absorption of organic compounds can be a valuable tool in drug design. Although Lipinski's 'rule of 5' is commonly used for this purpose, it does not routinely give reliable results. An alternative 'rule of unity' is proposed to predict the absorption efficiency of orally administered drugs that are passively transported. The rule of unity based upon the theoretical principals that govern passive transport. The 'rule of 5' and the 'rule of unity' are compared using experimentally determined passive human intestinal absorption data for 155 drugs. Absorption values which are >50% of the dose are classified as well absorbed and absorption values which are </=50% of the dose are classified as classified as poorly absorbed. Comparison of the two models using a receiver operating characteristic (ROC) plot and McNemar's test reveal striking differences in absorption predictability. The 'rule of 5' gives twice as many false predictions than the 'rule of unity.'
Algorithms↗