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At least 1,117 records · Page 62Linked to original sources
PubMed2002

Studies on intestinal absorption of sulpiride (1): carrier-mediated uptake of sulpiride in the human intestinal cell line Caco-2.

We investigated whether the uptake of a specific antipsychotic agent, sulpiride, in Caco-2 cells is mediated by a carrier-mediated system. Caco-2 cell monolayers were cultured in plastic culture dishes and uptake and efflux studies were conducted. The determination of sulpiride was performed by HPLC. At 37 degrees C, sulpiride uptake in pH 6.0 was twice as much as in pH 7.4. At 4 degrees C, however, no significant difference was observed between pH 6.0 and 7.4. The uptake at 4 degrees C was markedly lower than that obtained at 37 degrees C. The subtraction of the uptake at 4 degrees C from the uptake at 37 degrees C indicated a saturable process, and the result of the Eadie-Hofstee plot analysis indicated that the uptake consists of two or more saturable components. The uptake was significantly inhibited by uncoupler, protonophore, amino acid modifying agent and proteinase. Sulpiride efflux was temperature-dependent and was significantly inhibited by uncoupler and amino acid modifying agent. These findings indicate that sulpiride uptake and efflux in Caco-2 cells are carrier-mediated. Furthermore, the uptake was significantly decreased by some substrates and inhibitors of peptide transporter, PEPT1, and organic cation transporters, OCTN1 and OCTN2, and was significantly increased by preloading with them. The uptake was also significantly increased by a typical substrate of P-glycoprotein. From these findings, we presumed that peptide transporter PEPT1 and organic cation transporters OCTN1 and OCTN2 are involved with this uptake. P-glycoprotein may also contribute to the efflux of sulpiride.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats.

BACKGROUND: Inulin-type fructans or chains with mainly beta[2-1] linked fructose molecules escape the ingestion procedure in the small intestine and are fermented by the microflora, and are known to increase colonic absorption of minerals in animals. The fermentation rate in the large bowel into short-chain fatty acids depends on the molecular mass and the structure of these food ingredients. It is thought that this colonic fermentation is the basis for the reported increase in mineral absorption. AIM OF THE STUDY: The purpose of the present study was twofold: a) to compare different types of fructans that differ in the sugar chain length and in chain branching; b) to determine the potential synergistic effect of a combination of inulin-type fructans with different chain lengths. METHODS: For this purpose, 50 adult male Wistar rats weighing 170 g each were used in this study. The rats were distributed into 5 groups and fed for 28 days a fiber-free basal purified diet or diet containing 10 % oligofructose (OF) (DP(av) 4), or 10 % HP-inulin (DP(av) 25), a blend of 50 % OF and 50 % HP-inulin, or a branched-chain inulin. RESULTS: During the first period, the rats went into a gradual adaptation, during which the rats received 2.5 % for 1 week and then 5 % for 1 week of the tested products. During the last 4 days of the experiment, feces and urine were monitored for mineral balance study. The animals were then sacrificed and blood, cecum and tibia were sampled for mineral status assessment. Our results showed that the ingestion of all the tested fructans led to a considerable cecal fermentation. All tested compounds increased the intestinal absorption and balance of Mg significantly. Interestingly, in the present experimental set-up, all tested compounds increased the intestinal absorption and balance of Ca numerically, but only the blend OF + HP-inulin increased apparent intestinal absorption and balance of Ca significantly. CONCLUSIONS: The different types of fructans studied in the present experiment seem to have similar activity on mineral absorption. However, the combination of OF and HP-inulin showed synergistic effects on intestinal Ca absorption and balance in rats. Further studies with other combinations of fructans need to be done to extend these findings.

Analysis of Variance↗
PubMed2006

Effects of prenatal or postnatal ethanol consumption on zinc intestinal absorption and excretion in rats.

AIMS: The effect of ethanol consumption, either during the pregnancy or lactation period, on the altered metabolism of zinc is not well-defined; consequently, this study was performed to analyze the effect of chronic ethanol exposure on milk consumption, serum, milk, duodenal absorption, fecal and urinary excretion of zinc in dams and offspring during either gestation or lactation in the rat. A complementary study was performed regarding pregnancy outcome. We evaluated testosterone values, the offspring born/litter and several indices such as fertility, viable gestations and the survival index. METHODS: To study the effect of chronic alcoholism during gestation or lactation separately, at birth control newborns were cross-fostered to ethanol dams (ED), and the offspring issued from the ethanol treated mothers were cross-fostered to control dams (CD). Thus, three experimental groups of offspring were formed: (i) control offspring receiving no treatment (CO); (ii) offspring exposed to ethanol only during gestation (GO); and (iii) offspring exposed to ethanol only during lactation (LO). All the results were compared with offspring pair-fed groups (PFO) born of the pair-fed dams (PFD). RESULTS: Duodenal absorption of zinc increased significantly in LO offspring when the substrate concentrations in the perfusion medium were 25, 75, and 150 microM. A higher faecal excretion in GO pups compared with those with LO exposure and control groups (CO and PFO). The urine excretion of zinc was higher for LO offspring with respect to the other three experimental groups (CO, GO, and PFO). CONCLUSIONS: Maternal adaptation resulted in zinc retention, adequate to meet the demands of pup's growth in the face of a lower diet intake. The zinc status in pups is regulated by a higher absorption of zinc and intestinal conservation of endogenous fecal zinc after postnatal ethanol consumption. The increase in urinary zinc excretion could be responsible for decreased serum zinc. However, we found an increase in serum zinc probably due to an increase in the zinc absorption values.

Animals↗
PubMed1981

Increase of the intestinal absorption of gentamicin and amikacin by a nonionic surfactant.

This study was concerned with the effect of Cetomacrogol (polyethylene glycol 1000 monocetyl ether), a nonionic surfactant, on the absorption of gentamicin and amikacin from the gastrointestinal tract of rats. A 200-mg dose of Cetomacrogol coadministered orally with 10 mg of gentamicin resulted in a mean peak gentamicin blood concentration of 14.1 microgram/ml, compared with 67.8 microgram/mg when the same gentamicin dose was administered intramuscularly. The area under the curve after administration of the oral mixture was 23% of that after the intramuscular dose. The rectal administration of the mixture resulted in a mean peak gentamicin blood level of 8.2 micrograms/ml, compares to 16.5 microgram/ml when the mixture was administered orally. A 50-mg dose of amikacin coadministered orally with 200 mg of Cetomacrogol resulted in a mean peak amikacin blood level of 13.3 microgram/ml, compared to 310 microgram/ml when this amikacin dose was administered intramuscularly. Cetomacrogol augments the intestinal absorption of gentamicin and amikacin in rats. If the toxicity of the combination in humans is limited, the combination may be potentially clinically useful.

Amikacin↗
PubMed1995

Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses.

Single equimolar doses (0.5 mumol/kg body wt) of lutein and/or beta-carotene in true solution in oil were given to eight adult subjects and 13 blood samples were taken during the subsequent 840 h. Whereas the mean serum concentration of lutein showed a single maximum at 16 h, that of beta-carotene peaked at 6 h and then again at 32 h. Subsequently, lutein and beta-carotene were cleared at approximately the same rate from the serum. The mean (+/- SEM) areas under the curve (AUCs) for lutein and beta-carotene during the first 440 h differed significantly: 59.6 +/- 9.0 and 26.3 +/- 6.4 mumol.h/L, respectively (P < 0.005). AUC values did not correlate with initial serum concentrations of the given carotenoid or with the order of dosing. When combined in the same dose, beta-carotene significantly reduced the serum AUC values for lutein to 54-61% of control values (P < 0.025), whereas lutein reduced the AUC value for beta-carotene in five subjects but enhanced it in three subjects. Effects of lutein on the AUC for beta-carotene were inversely related to the AUC for beta-carotene alone. Thus, carotenoids clearly interact with each other during intestinal absorption, metabolism, and serum clearance, although individual responses can differ markedly.

Administration, Oral↗
PubMed1996

Local absorption kinetics into the portal system using the portal-venous concentration difference after an oral dose of diclofenac in the awakening rat. Accelerative effect of bile on intestinal absorption of diclofenac.

The local absorption kinetics from the intestinal tract into the portal system was evaluated using the portal-venous concentration difference (P-V difference) after oral administration of diclofenac in conscious rats. The local absorption ratio (Fa), mean local absorption time (ta), and relative variance (sigma 2/ta2) from the intestinal tract into the portal system were estimated by simultaneously measuring the portal and venous concentrations, using diclofenac as a model drug. The effect of bile on diclofenac intestinal absorption was also investigated. The awakening rats simultaneously cannulated into the jugular and portal veins were divided into group A with intact enterohepatic circulation (EHC) and into another group with bile-duct cannulation to block EHC. The rats in the latter group were further divided into group B without the bile supply to the intestinal tract and into group C with the bile supply from the other rat. After oral administration of diclofenac to rats in groups A, B, and C, the portal and venous concentrations of diclofenac in each rat were simultaneously monitored by HPLC method at proper time intervals. The absorption time profile of diclofenac into the portal system was directly predicted from P-V difference. Plasma concentrations of diclofenac in the portal vein were constantly higher than those in the jugular vein after the oral administration. It was demonstrated that P-V difference was caused by absorption from the intestinal tract into the portal system. Fa in groups A, B, and C were estimated to be 91.5% for 8 hr, 33.8% for 3 hr, and 57.8% for 3 hr, respectively. ta in groups A, B, and C were estimated to be 2.26 hr, 0.65 hr, and 0.96 hr, respectively. sigma 2/ta2 in groups A, B, and C were 1.31, 0.48, and 0.55, respectively. Fa and ta of diclofenac extensively increased in the presence of the bile in the intestinal tract, whereas sigma 2/ta2 was unaffected by the bile. The mean absorption time (MAT) almost agreed with ta, which demonstrates that the mean transit time through the liver (tH) is negligible in MAT(= ta+tH).

Administration, Oral↗
PubMed1991

The effect of acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats.

The intestinal transport of D-xylose was studied during the acute poisoning of male Wistar rats with orally administered potassium nitrate and sodium nitrite. At the peak of xylose absorption, the metabolic parameters of Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level were determined in the small intestine mucosa. Nitrite in a dose of 80 mg NaNO2/kg b.w. increased the permeability of gastric mucosa for D-xylose and raised the uptake of oxygen by the small intestine mucosa. No changes were observed in the activity of Na+/K(+)-ATPase and alkaline phosphatase. A dose of 10 mg NaNO2/kg b.w. was not followed by increased absorption of this sugar. It was also demonstrated that potassium nitrate had no effect on the process of intestinal absorption of D-xylose and failed to change the determined metabolic parameters of the small intestine mucosa.

Administration, Oral↗
PubMed2004

Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model.

In order to assess the risk to mammals of a chronic exposure to imidacloprid (IMI), we investigated its absorption with the human intestinal Caco-2 cell line. Measurements of transepithelial transport revealed an apparent permeability coefficient of 21.6 x 10(-6) +/- 3.2 x 10(-6) cm/s reflecting a 100% absorption. The comparison of apical to basal (A-B) and basal to apical (B-A) transports showed that the monolayer presents a basal to apical polarized transport. Studies of apical uptake demonstrated that the transport was concentration-dependent and not saturable from 5 to 200 microM. Arrhenius plot analysis revealed two apparent activation energies, Ea(4-12 degrees C) = 63.8 kJ/mol and Ea(12-37 degrees C) = 18.2 kJ/mol, suggesting two temperature-dependent processes. IMI uptake was equivalent when it was performed at pH 6.0 or 7.4. Depletion of Na+ from the transport buffer did not affect the uptake, indicating that a sodium-dependent transporter was not involved. Decrease of uptake with sodium-azide or after cell surface trypsin (Ti) treatment suggested the involvement of a trypsin-sensitive ATP-dependent transporter. Investigations on apical efflux demonstrated that initial velocities paralleled the increase of loading concentrations. A cell surface trypsin treatment did not affect the apical efflux. The lack of effect when the efflux was performed against an IMI concentration gradient suggested that an energy-dependent transporter was involved. However, the inhibition of P-glycoproteins (P-gp) and multidrug resistance-associated proteins (MRP) by taxol, vincristine, and daunorubicine had no effect on IMI intracellular accumulation suggesting the involvement of transporters distinct from classical ATP binding cassette transport (ABC-transport) systems. All results suggest that IMI is strongly absorbed in vivo by inward and outward active transporters.

Biological Transport↗
PubMed1991

Studies on the mechanism of the toxic action of sodium nitrite on intestinal absorption in rats.

The biochemical parameters Na+/K(+)-ATPase, alkaline phosphatase, oxygen consumption, and lactic acid level were evaluated in the small intestine mucosa of male Wistar rats during in situ perfusion of the rat with sodium nitrite. Sodium nitrite was poorly absorbed (10% of the administered dose), but it inhibited the activity of Na+/K(+)-ATPase and alkaline phosphatase. It had no effect on the lactic acid level, pointing to normal oxygen in the intestine, evidently reducing the utilization of oxygen by this tissue. Using metabolism inhibitors added to the perfusion fluid in the concentrations: ouabaine 0.1 mM, NaN3 (sodium azide) 1 mM, L-phenylalanine 50 mM and during functional ischaemia of the intestine produced by occlusion of the superior mesenteric artery for the time of the perfusion, it was possible to find the site of action and the direction of the toxic influence of sodium nitrite.

Alkaline Phosphatase↗
PubMed1996

Relationship between small-intestinal transit rate and intestinal absorption of (14)C-labelled mannitol and (51)Cr-labelled ethylenediaminetetraacetic acid in healthy subjects.

BACKGROUND: Although the small-intestinal transit rate is generally considered to influence the urinary excretion of markers of intestinal permeability, no study has until now formally addressed the importance of this influence in humans. METHODS: Ten healthy subjects ingested a test solution containing (99m)Tc-labelled diethylenetriaminepentaacetic acid ((99)mTc-DTPA), (14)C-labelled mannitol ((14)C-mannitol), and (51)Cr-labelled ethylenediaminetetraacetic acid ((51)Cr-EDTA). After ingestion, the small-intestinal transit rate of (99)mTc-DTPA was measured with the gamma camera technique. Urine was collected for time periods of 0-2 h, 2-4 h, and 4-6 h to measure the excretion of absorbed (14)C-mannitol and (51)Cr-EDTA. Moreover, the distribution volume and plasma clearance of (14)C-mannitol and (51)Cr-EDTA were determined in each subject. RESULTS: A positive correlation was found between mean small-intestinal transit time and 0- to 6-h urinary excretion of (14)C-mannitol. The study did not show any correlation between small-intestinal transit rate and 0- to 6-h urinary excretion of (51)Cr-EDTA. Urinary excretion of neither (14)C-mannitol nor (51)Cr-EDTA was affected by distribution volume or urine volume. A positive correlation was observed between plasma clearance and 0- to 6-h urinary excretion of (14)C-mannitol, whereas plasma clearance did not influence the urinary excretion of (51)Cr-EDTA. CONCLUSIONS: Small-intestinal transit rate seems to have a significant effect on 0- to 6-h urinary excretion of (14)C-mannitol, whereas small intestinal transit rate does not influence the timed urinary excretion of (51)Cr-EDTA.

Adult↗
PubMed1985

Localization of binding sites for concanavalin A, Ricinus communis I and Helix pomatia lectin in the Golgi apparatus of rat small intestinal absorptive cells.

Binding sites for concanvalin A (Con A), Ricinus communis I agglutinin (RCA I), and Helix pomatia lectin (HPA) were localized in the Golgi apparatus of rat small intestinal absorptive cells. A preembedment technique, a modification of the one originally used by Bernhard and Avrameas (Exp Cell Res 64:232, 1971), was employed, with horse-radish peroxidase being used for cytochemical visualization. Incubations were performed on 10 microns thick cryosections of duodenal segments that were fixed in a mixture of 4% formaldehyde and 0.5% glutaraldehyde; fixation was preceded by a 2-min rinse in 0.1 M sodium cacodylate and followed by storage in the same buffer for up to 7 days. Incubation with Con A, which binds preferably to alpha-D-mannose and alpha-D-glucose residues, caused intense reaction of the dilated cisternae of the cis Golgi side; staining was variable in intermediate and trans cisternae. RCA I, recognizing beta-D-galactose residues, could only be demonstrated in intermediate cisternae. Reaction for HPA, which indicates alpha-N-acetyl-D-galactosamine residues, stained intensely 1 to 2 cisternae of the cis Golgi side, as well as being localized in the peripheral regions of the cisternae of the intermediate compartment of the stacks. Deposits of reaction product covered the luminal surface of the cisternal membranes, but usually left the lumen itself, as well as lipid particles, devoid of reaction. The differences in Con A, RCA I, and HPA reactivity between cis, intermediate, and trans cisternae suggest compositional and structural differences of the carbohydrates in the respective compartments; they may reflect conversion processes that are known to occur in the oligosaccharide side chains of glycoconjugates at the Golgi complex level.

Absorption↗