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Small-intestinal absorption of cadmium and the significance of mucosal metallothionein.

1 Although food intake is among the most important routes of Cd exposure, not many details are known about the intestinal absorption mechanisms of Cd. In this respect Cd is representative of most other nonessential, merely toxic metals. 2 Based on a concept of two distinguishable steps, intestinal absorption of Cd is characterized by high accumulation within the intestinal mucosa and a low rate of diffusive transfer into the organism. 3 After uptake into the mammalian organism, Cd is sequestered into hepatic metallothionein (MT). It is assumed that hepatic Cd-MT then gradually redistributes Cd to the kidney, which is the main target organ for chronic Cd toxicity. 4 When feeding low levels of dietary CdCl2, however, Cd accumulates preferentially in the kidney and to a lesser degree in the liver, a distribution pattern also found after intravenous and peroral administration of the Cd-MT complex itself. As dietary Cd induces intestinal MT, intestinal Cd-MT complexes could be at least partly responsible for the renal accumulation of dietary Cd. 5 For this mechanism, however, serosal release of mucosal Cd-MT is required. In fact, in vitro findings in rats reveal a concentration-dependent release of intestinal MT to the serosal side of the small intestine. These results indicate that endogenous intestinal MT may deliver Cd-MT to other inner organs, thus contributing to the preferential renal accumulation of ingested Cd.

Animals↗

Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport.

Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.

Animals↗

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine.

The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi.

Dealkylation↗

Comparative effects of intestinal absorption of folic acid and methyltetrahydrofolic acid in chronic ethanol-fed rats.

This study concerns in vivo folic acid and methyltetrahydrofolic acid (MTHF) absorption by the whole intestinal surface after 20 weeks of 30% ethanol ingestion in drinking water. The results were compared with control rats fed ad libitum. The total intestinal serosal areas were similar in ethanol-fed and control rats. Significant increases in intestinal length, and decreases in tissue wet and dry weights were found in ethanol-fed rats. Serum folic acid concentrations were significantly less in the animals which had ingested ethanol than in the control rats. Intestinal folic acid absorption was significantly increased at lower substrate concentrations (0.5 and 1 microM), while no difference was observed at 2.5 microM in the ethanol-fed rats. Folic acid absorption relative to tissue wet weight showed significant increases at all tested concentrations in the ethanol-fed rats. Intestinal MTHF absorption showed no significant changes at 0.5 microM MTHF concentration, and an increase was observed in the absorption values at 1 and 2.5 microM concentrations in the ethanol-fed rats. When expressed as tissue wet weight, MTHF absorption values in ethanol-fed rats increased at 1 and 2.5 microM but did not differ at 0.5 microM substrate concentrations. The above results indicate compensatory responses in the folic acid and MTHF intestinal absorption after chronic ethanol ingestion. These effects are observed when the whole intestinal surface is evaluated.

Animals↗

Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars.

Animals↗

Early stages of intestinal absorption of specific antibiodies in the newborn. An ultrastructural, cytochemical, and immunological study in the pig, rat, and rabbit.

In mammals, passive immunity is transferred from mother to offspring by transplacental passage or by intestinal absorption. The rabbit receives antibodies exclusively across the placenta, whereas intestinal absorption is the principal source of antibodies for the new-born pig. In the rat, passive immunity is transferred by both pathways. The role of the jejunal absorptive cells was investigated in these three species, by the use of specific immune globulins as tracers of protein absorption. Rabbit anti-peroxidase and anti-ferritin antibodies were injected into the jejunum of newborn pigs, rats, and rabbits, and absorption was studied over the first 2 hr. The specific antibodies were detected in glutaraldehyde-fixed tissues after in vitro treatment with the antigens, and in sera by immunological methods. Intact antibodies are transferred into the circulation of the pig and the rat, but not into that of the rabbit. In the three species, the jejunal absorptive cells take up antibodies by endocytosis. In the pig, the antibodies are transported across the epithelium in vacuoles. In the rabbit, the endocytosis of antibodies triggers a lysosomal response and all absorbed antibodies are trapped in lysosomes. In the rat, both situations are found; there is no evidence of transfer of antibody fragments into the circulation.

Animals↗

Effect of verapamil on intestinal absorption of calcium in the rat.

The effect of verapamil in vitro, and the in vivo effect of both oral and parenteral verapamil administration on intestinal absorption was tested using everted gut sacs of duodenum, jejunum, distal ileum and proximal colon in rats. In the in vivo study, the effect of verapamil on blood levels of calcium, phosphorus and 1.25(OH)2D3, was investigated and a complete calcium balance was performed. In vitro, verapamil (1.5 mM) inhibited calcium absorption by the duodenum and colon only. Oral verapamil led to a reduction in the blood level of 1.25(OH)2D3. However, both oral and parenteral verapamil had no effect on the intestinal absorption, urinary secretion and consequently on the calcium balance.

Animals↗

Effect of phosphate on the intestinal absorption of lead (203Pb) in chicks.

The effect of phosphate on the intestinal absorption of lead (203Pb2+) was examined in chicks. Absorption was determined by the in situ ligated duodenal loop technique. In one approach, diets differing in phosphate content were fed to 2-week-old chicks for a period of 7 days. With respect to the control group (1.06% P), a severe phosphate deficiency (0.16% P) decreased growth, CaBP synthesis and 203Pb absorption; a moderate phosphate deficiency (0.33% P) resulted in an increase in CaBP production and 203Pb absorption; and the high phosphate diet (2.12%) gave mean values for CaBP synthesis and 203Pb absorption intermediate between those from the chicks fed the 0.33 and 1.06% diets. 203Pb absorption was highly correlated with CaBP concentrations. In another approach, phosphate in varying concentrations was added directly to the dosing solution. In one study, phosphate addition (0.1 mM) depressed 203Pb absorption in rachitic and cholecalciferol-treated chicks. When the data were expressed in terms of absorption of the soluble 203Pb present in the intestinal lumen at the end of the absorption period, an effect of phosphate in addition to the precipitation of the insoluble lead salt was uncovered. In an experiment with normal chicks, it was observed that phosphate in the dosing solution at concentrations of 1 and 2 mM partially and significantly reversed the inhibitory effect of lower concentrations of phosphate (0.01 mM and 0.1 mM). These data demonstrate the complexity of the phosphate-lead interaction, in addition to directly showing an effect of dietary phosphate on intestinal lead absorption.

Animals↗

Intestinal absorption of beta-alanine, anserine and carnosine in rats.

Absorption beta-alanine, anserine or carnosine from rat intestine was studied in vivo by a force feeding method and in vitro using an everted sac method. Possibility of anserine and carnosine hydrolysis prior to intestinal absorption was also investigated using a glycylleucine dipeptidase-containing fraction prepared from rat intestine. The following results were obtained. 1) Anserine and carnosine were absorbed as they were from rat small intestine. 2) Both anserine and carnosine were partially hydrolyzed in vitro by the glycylleucine dipeptidase-containing fraction. Carnosine was hydrolyzed faster than anserine. The above rather conflicting results suggest that physiological amounts of anserine and carnosine might be absorbed from rat small intestine in dipeptide forms.

Alanine↗

Intestinal transport and metabolism of analgesic dipeptide, kyotorphin: rate-limiting factor in intestinal absorption of peptide as drug.

Intestinal transport and metabolism of kyotorphin (KTP) were studied in rat everted small intestine. KTP on the mucosal side was metabolized completely within 60 min, and any amounts of KTP were not detected on the serosal side. On the other hand, [D-Arg2]-KTP (D-KTP) was stable on the mucosal side to appear on the serosal side. However, N-t-butoxycarbonyl-KTP (Boc-KTP), which was metabolized on the mucosal side faster than KTP, appeared on the serosal side. In intestinal homogenate, KTP was metabolized, and the metabolic clearance (CL(met)) was decreased by peptidase inhibitors, bestatin, o-phenanthrolin and tryptophan hydroxamate. In the presence of these peptidase inhibitors, the absorption clearance (CL(abs)) of KTP was increased. The less the CL(met) of KTP was, the more the CL(abs) of KTP was. Meanwhile, Boc-KTP in intestinal homogenate was stable even in the absence of peptidase inhibitors. The CL(abs) of Boc-KTP was constant irrespective of the stability on the mucosal side. Kinetic analysis by the metabolic inhibition model indicated that the stabilization of KTP in the intestinal tissue could increase the CL(abs) up to 0.247 microl/min per cm, which was as much as the CL(abs) of stable D-KTP. These results led to the conclusion that rate-limiting process in intestinal absorption of KTP is metabolic degradation in intestinal tissue during the absorption.

Analgesics↗

Some technical precisions to a method for in vivo intestinal absorption studies.

Some modifications to the method of PONZ et al. for in vivo intestinal absorption studies using an in situ perfused segment of small intestine, under anesthesia, are described. They improve its accuracy and applicability, especially when slowly absorbed substrates are used or when volume flux measurements are desired. Calculations for the absorbed substrate and net fluid volume change determinations are reported. Several aspects of the use of the method under a single pass or a recirculation perfusion system are discussed.

Animals↗

Effects of normal alcohols on intestinal absorption of salicylic acid, sulfapyridine, and prednisolone in rats.

The rates of intestinal absorption of salicyclic acid, sulfapyridine, and prednisolone from solutions containing no alcohol or 0.5% ethanol, n-butanol, or n-hexanol were determined. At the concentrations used, ethanol did not significantly affect drug absorption. Butanol reduced the rate of absorption of sulfapyridine but did not significantly affect the absorption rates of prednisolone or salicylic acid. Hexanol reduced the rates of absorption of sulfapyridine and salicylic acid and increased the rate of absorption of prednisolone. The absorption-altering effects of the alcohols were concentration dependent and rapidly reversible. Histological studies indicated that the structure of the epithelium was not altered by the alcohols. While the absorption rate of water from the drug solutions was increased by the alcohols, their absorption-altering effects could not be attributed solely to increased water flux. In addition, the absorption-altering effects of the alcohols could not be attributed to formation of drug-alcohol complexes nor to alcohol-induced alterations in the extent of binding of the drugs to nondialyzable materials in the intestinal drug solution.

Alcohols↗

[Intestinal absorption of D-xylose in children infected with the human immunodeficiency virus].

AIM: To evaluate the intestinal absorption in HIV-infected children children 14 months to 14 years and to investigate its relationship to diarrhea, nutritional status, immune dysfunction, classical enteric parasites and Cryptosporidium. METHODS: Intestinal absorption was investigated by measuring serum D-xylose. Fecal samples were investigated for classical pathogens and Cryptosporidium. The sample size was calculated considering a 30% prevalence of altered D-xylose absorption in HIV-infected children with a 5% accuracy. Statistical procedures used were: descriptive measurements, multiple correspondence analysis and logistic regression. RESULTS: D-xylose absorption was altered in only 8 out of 104 (7.7%) and Cryptosporidium was positive in 33 out of 104 (31.73%) HIV-infected children. The multiple correspondence analysis suggested an association between an altered D-xylose test and Cryptosporidium. D-xylose malabsorption was not associated with diarrhea, nutritional status, immune disfunction and classic enteric parasites. CONCLUSIONS: Intestinal malabsorption evaluated through the D-xylose test was an uncommon finding in HIV-infected children. Intestinal dysfunction when present seems to be related to Cryptosporidium, but not to diarrhea, nutritional status, immune disfunction and classic enteric parasites.

Adolescent↗

Intestinal absorption of calcium in vivo is dependent on endogenous nitric oxide.

This study examines the role of nitric oxide (NO) in the regulation of calcium absorption in the small intestine. Calcium absorption was quantified by measuring 45Ca++ transport from lumen to blood in an intestinal segment (duodenum and 20 cm of the proximal jejunum) perfused by both intraluminal and vascular routes in anesthetized rats. When administered i.v. as bolus injections, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg.kg-1), an inhibitor of NO biosynthesis, decreased calcium absorption with a concomitant increase in blood pressure and a decrease in mesenteric blood flow. Conversely, the nitrovasodilators 3-morpholinosydnonimine (2 mg.kg-1) and S-nitroso-N-acetylpenicillamine (10 micrograms.kg-1), which generate NO spontaneously, both increased calcium absorption with no change in mesenteric blood flow. When infused i.v., L-NAME (3 mg.hr-1.kg-1 for 40 min) induced a decrease in calcium absorption that was reversed by the NO donor sodium nitroprusside (1.5 mg.hr-1.kg-1 when infused for the last 20 min of the 40-min L-NAME infusion). Sodium nitroprusside infusion (1.5 mg.hr-1.kg-1) caused an increase in calcium absorption that was not reversed by L-NAME (3 and 30 mg.hr-1.kg-1). The present findings suggest that NO is involved in basal calcium absorption in rat small intestine in vivo.

Animals↗

Intestinal absorption of colostral lymphoid cells in newborn animals.

Intestinal absorption of colostral lymphoid cells was studied in 23 piglets of four sows and 17 lambs of ewes. From the colostrum and blood of the dams the lymphoid cells were isolated with Ficoll-Paque and labelled with technetium (Na99mTcO4). In the 7th hour after birth, 10 ml volume of the cell suspensions (piglets: 10(7) cells, lambs: 5 x 10(7) cells) were injected, following laparotomy, directly into the stomach or into the jejunum, or through a nasooesophageal tube. Cryostat sections of duodenum, jejunum and lymph node samples of animals were examined by autoradiography. It was found that lymphoid cells present in the colostrum of a piglet and lamb of their own mother were absorbed from the digestive tract and, via the lymphatic vessel, were transported to the mesenteric lypmph nodes. Electron microscopy revealed that absorption takes place intercellularly. Colostral cells of sows other than a piglet's own mother (allogeneic cells), the lymphoid cells isolated from the blood and heat-treated colostral lymphoid cells were not absorbed. The immunization of ewes and their lambs by tetanus anatoxin demonstrate, that the absorbed lymphoid cells remain immunologically active, and may transfer immune information to the lambs.

Animals↗

Intestinal absorption of specific structured triacylglycerols.

To clarify the intestinal absorption pathway of medium-chain fatty acids from MLM-type structured triacylglycerols containing both medium- and long-chain fatty acids, we studied the lymphatic transport of 1,3-dioctanoyl-2-linoleoyl-sn-glycerol (8:0/18:2/8:0), 1,3-didecanoyl-2-linoleoyl-sn-glycerol (10:0/18:2/10:0), and 1,3-didodecanoyl-2-linoleoyl-sn-glycerol (12:0/18:2/12:0) in a rat model. Safflower oil was used in the absorption study in order to compare the absorption of medium-chain fatty acids and long-chain fatty acids. The triacylglycerol species of lymph lipids were separated on a reversed-phase high performance liquid chromatograph (RP-HPLC) and identified by atmospheric pressure chemical ionization mass spectrometry. The composition of triacylglycerols was quantified by RP-HPLC with evaporative light scattering detection. The intact MLM-type triacylglycerols were detected in the lymph lipids after administration of the specific structured triacylglycerols (STAG). The recoveries of 8:0/18:2/8:0, 10:0/18:2/10:0, and 12:0/18:2/12:0 were 0.6%, 12%, and 5%, respectively. Several new triacylglycerol species were detected in the lymph lipids, including MLL-, LLL-, and MMM-type triacylglycerols. From the present study we conclude that the medium-chain fatty acids from STAG, in addition to absorption into the portal blood as free fatty acids, are absorbed by the same pathway as the conventional long-chain triacylglycerols, that is, they are hydrolyzed into free fatty acids, absorbed and activated into CoA, and reacylated into triacylglycerols in the enterocyte. The hydrolysis of MLM-type STAG is predominantly partial hydrolysis, whereas part of the STAG can also be hydrolyzed to free glycerol and free fatty acids.

Animals↗

ON THE USE OF TRITIUM-LABELLED ALBUMIN FOR STUDIES OF INTESTINAL ABSORPTION.

Human serum albumin has been successfully labelled with tritium. It is considerably denatured in the process and has a shorter half life when given intravenously than (131)I-labelled albumin. Nevertheless it is satisfactory for absorption studies, although not for turnover observations. These studies on absorption in control subjects and in patients with intestinal malabsorption indicate that the excreted radioactivity may have been derived from endogenous sources rather than from the results of malabsorption alone.

Biomedical Research↗