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Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model.

The purpose of this study was to investigate if the intestinal absorption of copper in drinking water is altered in the presence of complexing agents from a fulvic acid mixture and an infant formula powder. Ten to twelve day old rat pups were given a single oral dose of radio-labeled Cu in deionized water (0.93 mg Cu/l), in water containing fulvic acids (10 mg/l), in infant formula mixed with deionized water, or in infant formula mixed with water containing fulvic acids. Six hours after dosage, radioactive Cu was analyzed in the mucosa of the small intestine, the liver and the remaining carcass (excluding the liver and gastrointestinal tract) by gamma counting. Dialysis and centrifugation experiments showed that Cu was complexed by components in the fulvic acid and formula mixtures, although the presence of fulvic acids in the water did not alter the Cu fractionation in the formula. The fractional Cu uptake (% of dose) from the intestinal lumen to the mucosa was not markedly changed by the presence of the chelating agents. However, the retention of Cu in the intestinal mucosa was increased by both fulvic acids and formula. Concomitantly, the absorption rate of Cd to the circulatory system was decreased. No interactive effect between fulvic acids and formula was found on the Cu absorption. These findings indicate that the water quality may be an important determinant of the rate of intestinal Cu absorption from drinking water. Moreover, in the future risk assessment of copper in drinking water, the possibility of alterations in absorption of drinking-water Cu has to be considered when the drinking water is used for cooking.

Animals↗

Intestinal absorption and metabolism of 9-cis-beta-carotene in vivo: biosynthesis of 9-cis-retinoic acid.

This study was done to examine the intestinal absorption and cleavage of 9-cis-beta-carotene in vivo. A micellar solution, containing either no addition or 10 mumol of 9-cis- or all-trans-beta-carotene, was perfused for 2 h through the upper portion of the small intestine of ferrets. The effluent of a mesenteric lymph duct cannulation was collected, as well as intestinal mucosa scrapings, a portal blood sample, and a liver biopsy, both before and after perfusion. Carotenoids and retinoids were measured by reverse-phase, high performance liquid chromatography. 9-Cis- and all-trans-beta-carotene were transported equally well into mesenteric lymph, although the intestinal concentration of the corresponding isomer was tenfold higher after perfusion of the 9-cis- isomer than after perfusion of all-trans-beta-carotene. Regardless of which isomer was used, perfusion of beta-carotene resulted in the biosynthesis of similar amounts of retinoic acid in portal blood, liver, and intestine. However, after the perfusion of all-trans-beta-carotene, all the retinoic acid formed was in the all-trans- form, whereas the perfusion of 9-cis-beta-carotene resulted in the biosynthesis of about 50% of the total retinoic acid as the 9-cis-isomer. We conclude that in the in vivo ferret model, 9-cis-beta-carotene has a good bioavailability and is a precursor of 9-cis-retinoic acid.

Animals↗

[Evaluation of the intestinal absorption of iron orally administered as chondroitin sulfate in normal subjects].

The behaviour of sideremia has been studied in order to assess the intestinal absorption of iron of a new compound, ferric chondroitin sulfate after oral administration in 12 normal volunteers. After administration of 90 mg of iron as ferric chondroitin sulfate, sideremia rose from a basal value of 88 +/- 27 micrograms/dl to a value of 128 +/- 22 micrograms/dl at the third hour. Variance analysis showed that the increases were statistically significant (F = 27.7; p less than 0.00001). In the same subjects, the test was carried out in accordance with a randomised crossover design in two periods after administration of 91 mg of ferritin iron: sideremia rose from a basal value of 92 +/- 27 micrograms/dl to a value at the third hour of 97 +/- 28 micrograms/dl, moderate increases but statistically significant (F = 3.2; P = 0.0354). Variance analysis by repeated measurements showed that increases in sideremia were significantly higher after iron administration as ferric chondroitin sulfate than after administration of ferritin iron (F = 13.18; p = 0.0042). This study documents the good bioavailability of the iron contained in ferric chondroitin sulfate.

Administration, Oral↗

The effect of osmotic pressure on the intestinal absorption of sulfafurazol and ethanol in the rat.

The aim of the present study was to extend our earlier research into the effect of osmotic pressure on the intestinal absorption of drugs. In the experiments rats and an in situ technique were used. Sulfafurazol and ethanol were test substances and osmotic pressure was adjusted by NaCl, KNO3 or Na2SO4. From the results it was concluded that if all other factors are excluded the effect of the osmotic pressure of the vehicle is such that an isotonic solution has the best extent of bioavailability. Bioavailability decreases both when osmotic pressure decreases and when it increases. However, the decreasing effect of hypertonic solutions is stronger than that of hypotonic solutions. Although NaCl, KNO3 and Na2SO4, are often mentioned as alternative salts for adjusting osmotic pressure they are not equal in respect of their ability to alter the absorption of a drug.

Animals↗

Novel oral formulation safely improving intestinal absorption of poorly absorbable drugs: utilization of polyamines and bile acids.

In order to develop a novel oral formulation that can safely improve the intestinal absorption of poorly absorbable drugs, polyamines such as spermine (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in rats. The absorption of rebamipide, classified into BCS Class IV, from colon was significantly improved by SPM or SPD, and the enhancing ability of SPM was larger than that of SPD. As a possible mixing and/or interaction of polyamines with bile acids were expected, the combinatorial use of sodium taurocholate (STC) with polyamines was also examined. The absorption of rebamipide was drastically improved by the combinatorial use of SPM or SPD with STC. As STC itself did not enhance the absorption of rebamipide so much, it was considered that polyamines and STC had a synergistic enhancing effect. In-vivo oral absorption study was also performed to investigate the effectiveness and safety of polyamines and their combinatorial use with STC in rats. Although the enhancing effect slightly attenuated comparing with the in-situ loop study, the absorption of rebamipide was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC showed the largest enhancing effect. Histopathological studies clearly showed that any significant change in stomach and duodenum was not caused by SPM (10 mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h after oral administration. Taken all together, polyamines, especially SPM, and its combinatorial use with STC could improve the absorption of poorly absorbable drugs without any significant changes in gastrointestinal tract after oral administration in rats.

Adjuvants, Pharmaceutic↗

Intestinal absorption and secretion of radioactive vanadium (48VO3-) in rats and effect of Al(OH)3.

Vanadium in the metavanadate form (VO3-) is a powerful inhibitor of Na+, K+-ATPase. Because of the similarity between the oxy anions of vanadium and phosphorus, it was of interest to see whether Al(OH)3 would restrict the intestinal absorption of vanadium, as it does that of phosphorus. VO3- was extensively bound to a suspension of Al(OH)3 at pH 5-8. Sprague-Dawley rats (180-300 g) were fasted overnight and gavaged with 5 mumol Na3 VO4 in 1.0 ml 0.9% NaCl containing 1 microCi 48V. Control animals (n = 12) simultaneously received 1.0 ml diluent and experimental animals (n = 12) received 1 ml Al(OH))3. Diluent and Al(OH)3 were then given daily for 4 d. Urine and feces were collected separately each day. In control animals total 48V recovery (stool and urine) over 4 d was 86.6 +/- 2.4% of the administered dose. Although Al(OH)3 insignificantly increased total 48V recovery (93.6 +/- 3.2%), it markedly increased excretion of 48V in the stool as compared to the urine (control: stool, 69.1 +/- 1.8%; urine, 12.5 +/- 1.3%; Al(OH)3: stool, 85.7 +/- 1.5%; urine, 7.9 +/- 1.8%). Animals were then sacrificed and tissue uptake of tracer measured. The pattern of unexcreted 48V in tissue of both groups was kidney greater than bone greater than liver greater than intestine greater than muscle, but the tissue levels were uniformly higher in controls than in Al(OH)3-treated animals. The ability of Al(OH)3 to remove endogenous VO3- was also examined. 48V was injected ip (n = 20). Half of the animals received diluent and half received 1.0 ml Al(OH)3 by gavage daily for 4 d. There were no differences in the pattern of 48V tissue distribution and excretion. It is concluded that Al(OH)3 may prevent tissue accumulation of VO3- from dietary sources by reducing intestinal VO3- absorption.

Aluminum Hydroxide↗

Effect of cafeteria diet on alpha-MG intestinal absorption in rats.

The effect of a cafeteria diet (a hypercaloric diet) on the accumulative ability of the mediated and non-mediated small intestine transport of alpha-methyl-D-glucoside (alpha-MG) in developing female Wistar rats was studied using everted intestinal slices. Cafeteria diet increased intestinal active transport and decreased intestinal passive diffusion of alpha-MG in 30-day-old rats. No differences in alpha-MG intestinal absorption were found in cafeteria vs control rats after the development of obesity in cafeteria diet fed rats. A link between gastrointestinal functions and the development of obesity induced by cafeteria diet is suggested.

Animals↗

Intestinal absorption of ursodeoxycholic acid in patients with extrahepatic biliary obstruction and bile drainage.

Ursodeoxycholic acid (UDCA) dissolves cholesterol gallstones and improves liver function test results in patients with cholestatic liver diseases. Its absorption was studied in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but no intestinal or liver disease. Six patients received 500 mg chenodeoxycholic acid (CDCA) or 250-2000 mg UDCA in capsules in single oral doses in random order, with an interval of 2 days between the different treatment regimens. In the control period the patients excreted into bile 382.3 +/- 108.0 mumol CDCA (mean +/- SD) and 1866.7 +/- 172.6 mumol cholic acid per 24 hours. After administration of 1273.6 mumol (500 mg) CDCA, biliary excretion of this bile acid increased to 1370.9 +/- 185.7 mumol/24 h, indicating an intestinal absorption rate of 77.6% +/- 9.8%. After oral administration of 636.8 mumol (250 mg), 1273.6 mumol (500 mg), 2547.2 mumol (1000 mg), and 5094.4 mumol (2000 mg) of UDCA, the respective absorption rates were 60.3% +/- 7.4%, 47.7% +/- 9.0%, 30.7% +/- 7.5%, and 20.8% +/- 3.9%, and whereas in the control period no UDCA was detected in the bile, the UDCA percentages measured were 14.6% +/- 8.2%, 19.6% +/- 9.1%, 23.1% +/- 11.3%, and 27.4% +/- 12.1%. The coadministration of CDCA did not enhance the absorption of UDCA. The data indicate that absorption of orally administered CDCA is almost complete, whereas UDCA absorption is incomplete. With increasing doses UDCA absorption decreases. To achieve absorption of adequate amounts of UDCA, high and/or multiple doses are needed.

Administration, Oral↗

Epigallocatechin gallate and caffeine differentially inhibit the intestinal absorption of cholesterol and fat in ovariectomized rats.

We conducted this study to determine whether green tea constituents, (-)-epigallocatechin gallate (EGCG) and caffeine, affect the intestinal absorption of cholesterol (CH), fat, and other fat-soluble compounds. Ovariectomized rats with lymph cannula were infused intraduodenally with a lipid emulsion containing 14C-labeled CH (14C-CH), alpha-tocopherol (alpha TOH), triolein, and sodium taurocholate, without (control) or with EGCG, caffeine, or EGCG plus caffeine, in PBS, pH 6.5. The lymphatic total 14C-CH was significantly lowered by EGCG (21.1 +/- 2.1% dose), caffeine (27.9 +/- 1.7% dose), and EGCG plus caffeine (19.3 +/- 0.9% dose), compared with the control (32.4 +/- 1.6% dose). The lymphatic output of esterified CH also was significantly lower in rats infused with EGCG (7.9 +/- 0.7 micromol), caffeine (7.6 +/- 0.2 micromol), and EGCG plus caffeine (7.5 +/- 0.6 micromol) than rats in the control group (11.6 +/- 1.7 micromol). Also, EGCG and caffeine significantly lowered the absorption of alpha TOH, another highly hydrophobic lipid. However, the lymphatic outputs of oleic acid (exogenous fatty acid marker) and other fatty acids of endogenous origin were not affected by EGCG but were markedly lowered by caffeine and EGCG plus caffeine. Caffeine significantly lowered the amount of lymph flow, regardless of whether it was infused alone (14.2 +/- 3.9 mL) or with EGCG (18.6 +/- 2.0 mL), compared with EGCG (22.2 +/- 2.2 mL) alone and the control group (23.2 +/- 3.8 mL). The caffeine-induced decline in lymph flow was associated with the lowering of lipid absorption. The results indicate that both EGCG and caffeine inhibit lipid absorption and that the inhibitory effects of the 2 tea constituents are not synergistic but mediated by distinctly different mechanisms.

Animals↗

A simple test of intestinal absorption of calcium in rats.

We have developed a simple test of fractional calcium absorption in rats using oral 45Ca. The tracer was administered via a gastric tube, each animal receiving 0.15 microgram 45Ca with calcium glubionate as a carrier. Plasma radioactivity was determined at 30, 60, 90 and 120 min and expressed as percent dose in extracellular fluid. The fractional absorption of 45Ca was also expressed as 'area under the curve' (F45Ca) calculated by Simpson's approximation for each rat. The fractional absorption of calcium was determined in fasting and nonfasting fed animal subsets, each subset including control and rats treated with 1,25(OH)2D3. After 1,25(OH)2D3 administration, a significant increase in plasma calcium was seen in both fasting and fed animals. The fractional absorption of calcium was significantly higher in 1,25(OH)2D3-treated fasting as compared with control rats. In these animals, a positive correlation was found between F45Ca and plasma calcium. In contrast, in fed rats, the determined fractional absorption of calcium was similar in control and after 1,25(OH)2D3 administration. These results point to the use of orally administered 45Ca as a technically easy method for calcium absorption which can be used in most laboratories. In fasting animals it is sensitive enough for the evaluation of the effect of promoters of calcium absorption. The different findings in fed and fasting states may be related to the transmural processes which regulate the intestinal absorption of calcium.

Animals↗

Enhanced intestinal absorption of drugs by activation of peptide transporter PEPT1 using proton-releasing polymer.

Utilization of carrier-mediated transport systems in the gastrointestinal tract to increase the bioavailability of drugs is of great interest. In the present study, an increased supply of the driving force for peptide transporter PEPT1 by utilizing a proton-releasing polymer, Eudragit L100-55, was employed to increase the intestinal transport activity. Intestinal absorption of zwitterionic cefadroxil and dianionic cefixime was studied in rats by using in situ ileal closed loops and by in vivo oral administration of the drugs concomitantly with Eudragit L100-55. The results showed that Eudragit L100-55 decreased the pH in the intestinal loops, and increased the disappearance of both cefadroxil and cefixime from the loops. In rats, the plasma concentration after oral administration was increased significantly by coadministration of Eudragit L100-55, whereas a proton-nonreleasing analogous polymer, Eudragit RSPO, did not have any effect. Furthermore, the increased absorption of cefixime caused by Eudragit L100-55 was blocked by simultaneous administration of cefadroxil, a PEPT1 substrate/inhibitor, in a concentration-dependent manner. These results demonstrate that improvement of intestinal absorption of peptide-mimetics via a peptide transporter is possible by optimizing the transporter activity through coadministration of a proton-releasing polymer that supplies the driving force for the transporter.

Acrylic Resins↗

Intestinal absorption of lithocholic acid sulfates in the rat: inhibitory effects of calcium.

Sulfation of lithocholic acid has been proposed as a mechanism for elimination of this hepatotoxic bile acid from the body by accelerating its fecal excretion. However, quantitative data on the absorption characteristics of sulfated lithocholic acid conjugates in vivo are scarce. We studied the intestinal absorption of 14C-labeled glycolithocholic acid (GLC), taurolithocholic acid (TLC), and their 3 alpha-sulfate esters, SGLC and STLC, respectively. Studies were performed in unanesthetized rats with a permanent biliary drainage. At an intestinal infusion rate of 125 nmol/min, which is comparable to 7% of the normal biliary bile acid output in the rat, the absorption of sulfated lithocholic acid conjugates was delayed when compared with their unsulfated precursors but quantitatively only slightly reduced over a 24-h period: SGLC 90.9 +/- 3.6%, GLC 94.4 +/- 1.1%, STLC 84.4 +/- 3.0%, and TLC 94.2 +/- 2.1%. Urinary excretion of sulfated and unsulfated bile acids was similar and never exceeded 2% of the dose. SGLC absorption was dose dependent, was not altered by coinfusion of rat bile, and was only slightly reduced by a sixfold overdose of taurocholic acid. SGLC and STLC were excreted into bile largely unchanged in form. In contrast, GLC and TLC were extensively metabolized to more polar bile acids, predominantly to beta-muricholic acid conjugates. Replacement of NaCl in the infusion fluid by CaCl2 reduced the absorption of SGLC and STLC by 63 and 52%, respectively. This calcium effect was less pronounced for the unsulfated bile acids: GLC -22%, and TLC -19%. Absorption of taurocholic acid was unaffected by CaCl2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of sulphate- and bicarbonate-rich mineral waters on net and fractional intestinal absorption and urinary excretion of magnesium in rats.

Magnesium (Mg) intake is below the recommended daily allowances in many developed countries. Mg-rich mineral waters can provide significant amounts of energy-free Mg and thus help to meet Mg requirements. We assessed the effects of different Mg-rich mineral waters on overall intestinal Mg absorption and urinary Mg excretion in 40 rats split into four groups: one received distilled water, another a solution of MgCl(2) and the others two different mineral waters, sulphated water (Hépar) and carbonated water (Badoit) mixed with the diet and as drinking water, for four weeks. The rats were given 3 mg of (26)Mg orally and 0.5 mg of (25)Mg intravenously. They were placed in metabolic cages, and diet consumption, and faeces and urine excretion were monitored during the last four days of the experiment. The rats were then sacrificed and blood was sampled. Mg levels in the diet, faeces, urine and biological samples were measured by atomic absorption spectrometry. Mg stable isotope measurements were performed by ICP/MS. Mg-rich mineral waters significantly increased net intestinal absorption of Mg by more than 30%, but the proportions of both apparent and true intestinal absorption of Mg were similar in all four groups. Thus, net and fractional retention of Mg were similar in the three Mg-supplemented groups. In conclusion, both types of Mg-rich mineral waters studied similarly increased both absorption and urinary excretion of Mg with no positive effect on the overall retention of Mg, probably because the Mg status of the rats was already satisfactory.

Analysis of Variance↗

Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.

Triglycerides and cholesterol are important biological lipids, and their excessive intake in the diet is relevant to the development of two prevalent cardiovascular risk factors, obesity and hypercholesterolemia. Because most lipids are essentially water-insoluble molecules, their transport within and absorption from the aqueous medium of intestinal contents is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific esterases, micellar transport, mucosal absorption, re-synthesis of parent molecules in enterocytes, and assembly with apolipoproteins and other molecules to form chylomicrons, the secretory product of intestinal cells. Many of these processes, however, are not well characterized at the molecular level. While in health the intestinal absorption of triglycerides is very efficient, the same does not apply to cholesterol absorption. Besides being generally inefficient, cholesterol absorption is highly variable, with a between-subject variability that depends in part on genetic factors and an intra-individual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal lipid absorption can be interfered with by dietary components or drugs and thus are potential therapeutic targets for inducing a controlled malabsorption of triglyceride, useful in the treatment of obesity, or for rendering cholesterol absorption even more inefficient in an attempt to lower blood cholesterol levels. Nevertheless, intestinally derived cholesterol available to the liver exerts complex feedback regulation on whole-body cholesterol homeostasis that limits the efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This review focuses first on present knowledge of the physiology of intestinal fat absorption, necessary to understand the ways to manipulate it in order to obtain the desired effects on dietary triglyceride and cholesterol disposition. The second part discusses old, present and future ways, both dietary and pharmacological. of interfering with cholesterol and triglyceride absorption to reduce blood cholesterol and energy acquisition, respectively.

Animals↗

Intestinal absorption and fecal excretion of 5,6 alpha-epoxy-5 alpha-cholesta-3 beta-ol by the male Wistar rat.

The intestinal absorption of 5,6 alpha-epoxy-5 alpha-cholesta-3 beta-ol, an oxysterol formed by cholesterol autoxidation, has been evaluated in the male Wistar rat. Measurement of the 14C/3H ratio in the serum (by the method of Zilversmit and Hugues) and in the feces showed that a large proportion of the epoxide was absorbed. Epoxide clearance from the blood was very rapid, but its excretion in the stool continued for several days, corresponding to the fraction of the epoxide stored in the animal.

Animals↗

Further studies on the perfusion method for measuring intestinal absorption in man: the effects of a proximal occlusive balloon and a mixing segment.

The reliability and accuracy of the two-lumen tube perfusion method for measuring intestinal absorption in man has been assessed by the use of a proximal occlusive balloon in nine normal volunteers. Luminal occlusion significantly reduced the variability of individual glucose and water absorption rates, and reduced the variability of triplicate marker concentrations within individual studies. Mean absorption rates of glucose, water, sodium, and chloride were not significantly affected by luminal occlusion. Absorption rates obtained with the triple-lumen tube method were rather more variable both within and between individuals, but a statistical comparison of the accuracy of the two methods could not be made. These results are discussed in relation to the contribution of endogenous gut secretion and proximal reflux of infused fluid to the variability of absorption rates obtained by the perfusion technique.

Adult↗

Effect of alpha-glucosidehydrolase inhibition and intestinal absorption of sucrose, water, and sodium in man.

The effect of a new complex oligosaccharide exhibiting potent inhibitory action on alpha-glucoside hydrolases on intestinal absorption of sucrose in man was tested by constant in vivo perfusion of the jejunum. At concentrations of 4.65 or 15.5 X 10(-6)M the alpha-glucosidehydrolase inhibitor (alpha-GHI) markedly inhibited absorption of glucose from sucrose and absorption of sodium and water. Oral administration of the alpha-GHI resulted as well in depression of solute, sodium, and water absorption. This new compound can serve as an interesting tool to induce carbohydrate malabsorption by inhibition of final digestion and may possibly be of beneficial therapeutic effect in dietary control of diabetes or obesity.

Adult↗