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Sample records for intestinal oxalate absorption

  1. Regional differences in oxalate absorption by rat intestine: evidence for excessive absorption by the colon in steatorrhoea.

    PubMed Central

    Saunders, D R; Sillery, J; McDonald, G B

    1975-01-01

    Clinical studies suggest that steatorrhoea can be associated with excessive absorption of dietary oxalate. We examined the influence of bile salts, Ca++, and long-chain fatty acid on the absorption of oxalate and water by rat intestine in vivo. Absorption was measured under steady-state conditions during single-pass infusions. Each intestinal segment served as its own control. In jejunum, 10 mM taurocholate, the principal salt in rat bile, depressed absorption of oxalate and water. Absorption was not depressed further by Ca++ or linoleic acid. In ileum, 10 mM taurocholate did not inhibit absorption. Linoleic acid, 2 mM, depressed absorption of both oxalate and water. In colon 10 mM taurocholate decreased absorption. Net water transport was depressed further when linoleic acid was added to the infusion, but oxalate absorption was enhanced. Ca++ negated these effects of linoleic acid. It is concluded that long-chain fatty acids may enhance the absorption of oxalate from the rat colon. This observation may be relevant to understanding hyperoxaluria in patients with steatorrhoea. PMID:1158192

  2. Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

    PubMed

    Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

    2017-01-01

    Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr(-/-) mice in Ussing chambers and measured transcellular secretion of [(14)C]oxalate. Intestinal tissue isolated from Cftr(-/-) mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr(-/-) tissue. Compared with wild-type mice, Cftr(-/-) mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl(-)-oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr(-/-) mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.

  3. Absorption kinetics of oxalate from oxalate-rich food in man.

    PubMed

    Prenen, J A; Boer, P; Dorhout Mees, E J

    1984-11-01

    The absorption of oxalate was investigated in a healthy subject after ingestion of oxalate-rich meals (spinach and rhubarb) with and without addition of 14C-labeled oxalic acid and calcium oxalate, and after oxalate-free meals with addition of nonlabeled sodium oxalate and calcium oxalate. Under these conditions, calcium oxalate was absorbed to the same extent as soluble oxalate; only a small percentage (2.4 +/- 0.7) of the total oxalate load was absorbed. Significant oxalate absorption occurred within 1 to 8 h after ingestion. The results suggest that under normal conditions the proximal part of the small bowel is a major absorption site.

  4. Oxalic acid decreases calcium absorption in rats

    SciTech Connect

    Weaver, C.M.; Martin, B.R.; Ebner, J.S.; Krueger, C.A.

    1987-11-01

    Calcium absorption from salts and foods intrinsically labeled with /sup 45/Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO/sub 3/ and CaCl/sub 2/ than from CaC/sub 2/O/sub 4/ (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

  5. Oxalic acid decreases calcium absorption in rats.

    PubMed

    Weaver, C M; Martin, B R; Ebner, J S; Krueger, C A

    1987-11-01

    Calcium absorption from salts and foods intrinsically labeled with 45Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO3 and CaCl2 than from CaC2O4 (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

  6. Probiotics and Other Key Determinants of Dietary Oxalate Absorption1

    PubMed Central

    Liebman, Michael; Al-Wahsh, Ismail A.

    2011-01-01

    Oxalate is a common component of many foods of plant origin, including nuts, fruits, vegetables, grains, and legumes, and is typically present as a salt of oxalic acid. Because virtually all absorbed oxalic acid is excreted in the urine and hyperoxaluria is known to be a considerable risk factor for urolithiasis, it is important to understand the factors that have the potential to alter the efficiency of oxalate absorption. Oxalate bioavailability, a term that has been used to refer to that portion of food-derived oxalate that is absorbed from the gastrointestinal tract (GIT), is estimated to range from 2 to 15% for different foods. Oxalate bioavailability appears to be decreased by concomitant food ingestion due to interactions between oxalate and coingested food components that likely result in less oxalic acid remaining in a soluble form. There is a lack of consensus in the literature as to whether efficiency of oxalate absorption is dependent on the proportion of total dietary oxalate that is in a soluble form. However, studies that directly compared foods of varying soluble oxalate contents have generally supported the proposition that the amount of soluble oxalate in food is an important determinant of oxalate bioavailability. Oxalate degradation by oxalate-degrading bacteria within the GIT is another key factor that could affect oxalate absorption and degree of oxaluria. Studies that have assessed the efficacy of oral ingestion of probiotics that provide bacteria with oxalate-degrading capacity have led to promising but generally mixed results, and this remains a fertile area for future studies. PMID:22332057

  7. The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2017-02-01

    The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans.

  8. Physiology of Intestinal Absorption and Secretion

    PubMed Central

    Kiela, Pawel R.; Ghishan, Fayez K.

    2016-01-01

    Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipidand water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms. PMID:27086882

  9. Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter.

    PubMed

    Hatch, Marguerite; Gjymishka, Altin; Salido, Eduardo C; Allison, Milton J; Freel, Robert W

    2011-03-01

    Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691-698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals.

  10. The Intestinal Absorption of Folates

    PubMed Central

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I. David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

  11. Incomplete intestinal absorption of fructose.

    PubMed Central

    Kneepkens, C M; Vonk, R J; Fernandes, J

    1984-01-01

    Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children. PMID:6476870

  12. Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption.

    PubMed

    Goncalves, Aurélie; Roi, Stéphanie; Nowicki, Marion; Dhaussy, Amélie; Huertas, Alain; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2015-04-01

    The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal-colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

  13. Neural regulation of intestinal nutrient absorption.

    PubMed

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

    The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function.

  14. Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation.

    PubMed

    Amin, Ruhul; Sharma, Sapna; Ratakonda, Sireesha; Hassan, Hatim A

    2013-07-01

    Nephrolithiasis remains a major health problem in Western countries. Seventy to 80% of kidney stones are composed of calcium oxalate, and small changes in urinary oxalate affect risk of kidney stone formation. Intestinal oxalate secretion mediated by the anion exchanger SLC26A6 plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis, indicating that understanding the mechanisms regulating intestinal oxalate transport is critical for management of hyperoxaluria. Purinergic signaling modulates several intestinal processes through pathways including PKC activation, which we previously found to inhibit Slc26a6 activity in mouse duodenal tissue. We therefore examined whether purinergic stimulation with ATP and UTP affects oxalate transport by human intestinal Caco-2-BBe (C2) cells. We measured [¹⁴C]oxalate uptake in the presence of an outward Cl⁻ gradient as an assay of Cl⁻/oxalate exchange activity, ≥50% of which is mediated by SLC26A6. We found that ATP and UTP significantly inhibited oxalate transport by C2 cells, an effect blocked by the PKC inhibitor Gö-6983. Utilizing pharmacological agonists and antagonists, as well as PKC-δ knockdown studies, we observed that ATP inhibits oxalate transport through the P2Y₂ receptor, PLC, and PKC-δ. Biotinylation studies showed that ATP inhibits oxalate transport by lowering SLC26A6 surface expression. These findings are of potential relevance to pathophysiology of inflammatory bowel disease-associated hyperoxaluria, where supraphysiological levels of ATP/UTP are expected and overexpression of the P2Y₂ receptor has been reported. We conclude that ATP and UTP inhibit oxalate transport by lowering SLC26A6 surface expression in C2 cells through signaling pathways including the P2Y₂ purinergic receptor, PLC, and PKC-δ.

  15. Vitamin D and intestinal calcium absorption.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

  16. Circadian regulators of intestinal lipid absorption

    PubMed Central

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption. PMID:25057097

  17. Influence of magnesium on the absorption and excretion of calcium and oxalate ions.

    PubMed

    Berg, W; Bothor, C; Pirlich, W; Janitzky, V

    1986-01-01

    In two test series additional oxalic acid excretion in urine was induced in healthy test persons by administering a spinach diet. This additional excretion could be markedly reduced by magnesium administration. Calcium and citrate excretions are largely unaffected by magnesium administration. Magnesium excretions, however, are clearly increased. The calcium oxalate crystallization rates in the 5-or 7-hour urines reveal a behavior parallel to that of the oxalic acid excretion profile. In the control urines, the crystal picture is characterized by numerous medium-sized whewellite crystals. In contrast, in the test series weddellite crystals are reduced in size and frequency after magnesium administration. New aspects of magnesium effects must be discussed; above all the possible absorption changes resulting from gastrointestinal diseases.

  18. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  19. Biotin absorption by distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1987-12-01

    We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin.

  20. Intestinal absorption of aluminium in renal failure.

    PubMed

    Drüeke, Tilman B

    2002-01-01

    The proportion of the daily ingested aluminium that is absorbed in the intestinal tract has remained a matter of debate for many years because no reliable method of measurement was available. Studies with earlier analytic techniques reported fractional absorption of aluminium from as little as 0.001% to as much as 27% of an oral dose. Measurement of (26)Al by high-energy accelerator mass spectrometry has permitted more accurate analyses. In normal young rats, 0.05-0.1% of ingested aluminium is absorbed in the intestine, of which roughly half goes to the skeleton within 2 h, whereas the remaining half is excreted in the urine, most of it within 48 h. Deposition in organs other than the skeleton appears to be negligible. In healthy human volunteers, the most recent estimates of fractional intestinal (26)Al absorption were also in the range of 0.06-0.1%. In both rats and humans, intestinal absorption of aluminium is subject to many systemic and local factors. The latter include various compounds with which aluminium is complexed in the gut lumen, and gastric acidity. The influence of food is controversial; however, absorption appears higher in the fasted than the post-prandial state. Luminal phosphate concentration decreases aluminium absorption, whereas citrate increases it. For theoretical reasons, silicates should prevent aluminium absorption, but experimental evidence has not supported this theory. Whether water hardness affects aluminium bioavailability remains a matter of debate. General conditions may also modify aluminium absorption and deposition in bone. Examples of these general factors include the uraemic syndrome, diabetes mellitus, secondary hyperparathyroidism, vitamin D status, Alzheimer's disease and Down's syndrome. Awareness of intestinal absorption of aluminium is particularly important, given that aluminium-based binders continue to be used in uraemic patients, despite the hazards of aluminium accumulation. The lessons we have learned about

  1. Effect of sodium chenodeoxycholate on oxalate absorption from the excluded human colon--a mechanism for 'enteric' hyperoxaluria.

    PubMed Central

    Fairclough, P D; Feest, T G; Chadwick, V S; Clark, M L

    1977-01-01

    A perfusion technique has been used to study the effect of sodium chenodeoxycholate (5 mmol 1-1) on absorption of oxalate (2 mmol 1-1) from the surgically excluded colon in two patients with chronic liver disease. Colonic absorption of oxalate increased at least fivefold when sodium chenodeoxycholate was incorporated in the perfusion solutions. This observation may explain enteric hyperoxaluria after ileal resection and in some other gastrointestinal disorders. PMID:852753

  2. Intestinal absorption of calcium and phosphorus

    SciTech Connect

    Wasserman, R.H.

    1981-01-01

    The intestinal absorption of calcium and phosphorus has received considerable attention in recent years. The evidence has clearly indicated that calcium is absorbed by two processes: active transport and diffusion. Vitamin D appears to affect both processes, and has a significant effect at the brush border of the intestinal cell. Several proposed models to account for the transmural movement of calcium are discussed. The active transport of phosphate is under the control of vitamin D and is located at the brush border region of the intestinal cell. This transport system, like several others, appears to be sodium-dependent and inhibited by ouabain. In-transit phosphate does not mix with the cellular phosphate pool. Emphasized in the presentation is current knowledge of the transport mechanisms and macromolecular changes that potentially account for the stimulatory effect of vitamin D on calcium and phosphate transport.

  3. Iron absorption by small intestine of chickens.

    PubMed

    Sáiz, M P; Martí, M T; Mitjavila, M T; Planas, J

    1993-01-01

    Iron (Fe) absorption by three segments (duodenum, jejunum, and ileum) of the small intestine of chickens was studied by a perfusion technique in vivo in closed circuit using 59Fe Cl3 and was related to the histological characteristics of each segment. The serosal transfers of Fe for the duodenum and jejunum were the same (14%/cm), but significantly different (p < 0.05) from those of the ileum (9%/cm), which may be explained by the morphological and histological properties of the gut of chickens. However, the presence of Fe in blood and in liver was significantly lower after perfusion of the jejunum and ileum than after perfusion of the duodenum. It is concluded that chickens show an early adaptation of small intestine to Fe absorption in response to the considerable loss of Fe suffered during the laying process.

  4. Dietary Phospholipids and Intestinal Cholesterol Absorption

    PubMed Central

    Cohn, Jeffrey S.; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W. S.; Tandy, Sally

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the ability of PLs to inhibit cholesterol absorption is of therapeutic benefit. PMID:22254012

  5. Disorders of intestinal secretion and absorption.

    PubMed

    Schulzke, Jörg-Dieter; Tröger, Hanno; Amasheh, Maren

    2009-01-01

    The gastrointestinal tract possesses a huge epithelial surface area and performs many different tasks. Amongst them are the digestive and absorptive functions. Disorders of intestinal absorption and secretion comprise a variety of different diseases, e.g. coeliac disease, lactase deficiency or Whipple's disease. In principle, impaired small intestinal function can occur with or without morphological alterations of the intestinal mucosa. Therefore, in the work up of a malabsorptive syndrome an early small intestinal biopsy is encouraged in conjunction with breath tests and stool analysis to guide further management. In addition, there is an array of functional tests, the clinical availability of which becomes more and more limited. In any case, early diagnosis of the underlying pathophysiology is most important, in order to initiate proper therapy. In this chapter, diagnostic procedure of malabsorption is discussed with special attention to specific disease like coeliac disease, Whipple's disease, giardiasis and short bowel syndrome. Furthermore, bacterial overgrowth, carbohydrate malabsorption and specific nutrient malabsorption (e.g. for iron or vitamins) and protein-losing enteropathy are presented with obligatory and optional tests as used in the clinical setting.

  6. Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption.

    PubMed

    Hui, David Y; Labonté, Eric D; Howles, Philip N

    2008-04-01

    Intestinal cholesterol absorption is modulated by transport proteins in enterocytes. Cholesterol uptake from intestinal lumen requires several proteins on apical brush-border membranes, including Niemann-Pick C1-like 1 (NPC1L1), scavenger receptor B-I, and CD36, whereas two ATP-binding cassette half transporters, ABCG5 and ABCG8, on apical membranes work together for cholesterol efflux back to the intestinal lumen to limit cholesterol absorption. NPC1L1 is essential for cholesterol absorption, but its function as a cell surface transporter or an intracellular cholesterol transport protein needs clarification. Another ATP transporter, ABCA1, is present in the basolateral membrane to mediate HDL secretion from enterocytes.

  7. Intestinal Lipid Absorption and Lipoprotein Formation

    PubMed Central

    Hussain, M. Mahmood

    2014-01-01

    Purpose of review The purpose of this review is to summarize evidence for the presence of two pathways of lipid absorption and their regulation. Recent findings Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine followed by the uptake of hydrolyzed products by enterocytes. Lipids are re-synthesized in the endoplasmic reticulum and are either secreted with chylomicrons and high density lipoproteins or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are critically dependent on MTP and ABCA1, respectively, and are regulated independently. Gene ablation studies showed that MTP function and chylomicron assembly is essential for the absorption of triglyceride and retinyl esters. Ablation of MTP abolishes triglyceride absorption and results in massive triglyceride accumulation in enterocytes. Although majority of phospholipid, cholesterol and vitamin E are absorbed through the chylomicron pathway, a significant amount of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and secretion is increased by the enhanced availability of fatty acids, whereas HDL pathway is upregulated by LXR agonists. Intestinal insulin resistance increases chylomicron and might reduce HDL production. Summary Triglycerides are exclusively transported via the chylomicron pathway and this process is critically dependent on MTP. Besides chylomicrons, absorption of phospholipids, free cholesterol, retinol, and vitamin E also involves high density lipoproteins. These two pathways are complementary and are regulated independently. They may be targeted to lower lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis and other disorders. PMID:24751933

  8. Intestinal absorption of biotin in the rat

    SciTech Connect

    Bowman, B.B.; Selhub, J.; Rosenberg, I.H.

    1986-07-01

    We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing (/sup 3/H)biotin and (/sup 14/C)inulin in Krebs-Ringer phosphate buffer, pH 6.5. Absorption was determined on the basis of luminal tritium disappearance after correction for inulin recovery. At biotin concentrations of 0.1 and 5.0 microM, luminal biotin disappearance was linear for at least 10 min. At biotin concentrations ranging from 2.3 nM to 75 microM, 10-28% of the administered dose was absorbed in 10 min. The concentration dependence of luminal biotin disappearance is consistent with the presence of both saturable and nonsaturable (linear) components of biotin uptake, with estimated Km = 9.6 microM and Jmax = 75.2 pmol/(2.5 cm loop X min). The rate constant for nonsaturable uptake is 3.1 pmol/(2.5 cm loop X min X microM). We conclude that at biotin concentrations less than 5 microM, biotin absorption proceeds largely by the saturable process, whereas at concentrations above 25 microM, nonsaturable uptake predominates. Additional studies demonstrated significantly less biotin uptake in the ileum than in the jejunum, a finding in agreement with previous in vitro studies.

  9. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    SciTech Connect

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  10. INTESTINAL TRIGLYCERIDE ABSORPTION IN THE RAT

    PubMed Central

    Cardell, Robert R.; Badenhausen, Susan; Porter, Keith R.

    1967-01-01

    This report provides information on the morphology of fat absorption in rat intestinal epithelial cells. Three types of experiments were performed: (a) intubation of corn oil into fasted rats, (b) injection of physiological fatty-chyme prepared from fat-fed donor rats into ligated segments of jejunum of fasted animals, and (c) administration of electron-opaque particles in corn oil and markers given concurrently with the fat. These results support the hypothesis that fat is absorbed by selective diffusion of monoglycerides and fatty acids from micelles rather than by pinocytosis of unhydrolized triglycerides. Evidence is presented that the pits between the microvilli, previously believed to function in the transport of fat, are not involved in this process. Instead they appear to contribute their contents to lysosomes in the apical cytoplasm. Arguments are offered that the monoglycerides and fatty acids diffuse from the micelle while the latter is associated with the microvillous membrane of the absorptive cell. These micellar components penetrate the plasma membrane and diffuse into the cytoplasmic matrix where they encounter the SER. Triglyceride synthesis occurs in the SER and results in the deposition of fat droplets within its lumina. The synthesis of triglycerides and their sequestration into the SER establishes an inward diffusion gradient of monoglycerides and fatty acids. PMID:6033529

  11. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    PubMed

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.

  12. Intestinal absorption of berberine and 8-hydroxy dihydroberberine and their effects on sugar absorption in rat small intestine.

    PubMed

    Wei, Shi-chao; Dong, Su; Xu, Li-jun; Zhang, Chen-yu

    2014-04-01

    The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

  13. Models to predict intestinal absorption of therapeutic peptides and proteins.

    PubMed

    Antunes, Filipa; Andrade, Fernanda; Ferreira, Domingos; Nielsen, Hanne Morck; Sarmento, Bruno

    2013-01-01

    Prediction of human intestinal absorption is a major goal in the design, optimization, and selection of drugs intended for oral delivery, in particular proteins, which possess intrinsic poor transport across intestinal epithelium. There are various techniques currently employed to evaluate the extension of protein absorption in the different phases of drug discovery and development. Screening protocols to evaluate protein absorption include a range of preclinical methodologies like in silico, in vitro, in situ, ex vivo and in vivo. It is the careful and critical use of these techniques that can help to identify drug candidates, which most probably will be well absorbed from the human intestinal tract. It is well recognized that the human intestinal permeability cannot be accurately predicted based on a single preclinical method. However, the present social and scientific concerns about the animal well care as well as the pharmaceutical industries need for rapid, cheap and reliable models predicting bioavailability give reasons for using methods providing an appropriate correlation between results of in vivo and in vitro drug absorption. The aim of this review is to describe and compare in silico, in vitro, in situ, ex vivo and in vivo methods used to predict human intestinal absorption, giving a special attention to the intestinal absorption of therapeutic peptides and proteins.

  14. Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.

    PubMed

    Holmstock, Nico; De Bruyn, Tom; Bevernage, Jan; Annaert, Pieter; Mols, Raf; Tack, Jan; Augustijns, Patrick

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption.

  15. Fractional magnesium absorption is significantly lower in human subjects from a meal served with an oxalate-rich vegetable, spinach, as compared with a meal served with kale, a vegetable with a low oxalate content.

    PubMed

    Bohn, Torsten; Davidsson, Lena; Walczyk, Thomas; Hurrell, Richard F

    2004-04-01

    The aim of the present study was to evaluate Mg absorption from a test meal served with an oxalate-rich vegetable, spinach, as compared with a test meal served with a vegetable with a low oxalate content, kale. Mg absorption was measured by a stable-isotope technique based on extrinsic labelling of the test meals and faecal monitoring of the excreted isotope labels. Nine healthy adults participated in the study. The test meals were based on 100 g phytate-free white bread, served with 300 g spinach (6.6 mmol oxalate; 0.7 mmol (25)Mg label added, 5.0 mmol total Mg) or 300 g kale (0.1 mmol oxalate; 1.2 mmol (26)Mg label added, 4.8 mmol total Mg). The test meals were served on days 1 and 3, at breakfast and lunch, using a cross-over design. The results from the present study demonstrated that apparent Mg absorption was significantly lower from the meal served with spinach (26.7 (sd 10.4) %) than the meal served with kale (36.5 (sd 11.8) %) (P=0.01). However, the lower fractional apparent Mg absorption from the test meal served with spinach can be assumed to be, at least partly, counterbalanced by the higher native Mg content of spinach as compared with kale. Although based on indirect evidence, i.e. not based on an evaluation of added (or removed) oxalic acid, the difference in Mg absorption observed in the present study is attributed to the difference in oxalic acid content between the two vegetables.

  16. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

    Dowling, H.J.; Offenbacher, E.G.; Pi-Sunyer, F.X.

    1986-03-01

    The mechanism of chromium (Cr) absorption by the rat small intestine was investigated using a double perfusion technique wherein the luman of the small intestine and the vasculature supplying it were separately perfused. The intestinal perfusate (IP) was a nutrient-rich tissue culture medium (TCM) with added inorganic Cr and /sup 51/Cr. The vascular perfusate (VP) was a Krebs-Ringer bicarbonate solution (KRB) containing 4.7% dextran, 0.1% glucose and 5% human serum. Cr absorption was calculated by the amount of /sup 51/Cr detected in the VP. To determine the transport mechanism for Cr, its absorption into the VP was measured at various Cr concentrations of the IP ranging from 10-400 ppb CrCl/sub 3/. The amount of Cr absorbed into the blood rose linearly with the intestinal Cr concentration suggesting a process of simple diffusion. Manipulations of the VP and IP constituents were made to investigate their effects on Cr absorption. When serum was omitted from the VP, Cr adsorption was suppressed, suggesting that serum component(s) are necessary for optimal Cr absorption. When either of 2 plasma transport proteins (apo-transferrin, albumin) were added to the serum-free VP at physiological levels, Cr absorption returned to, but did not exceed, control levels. When the TCM was replaced with a KRB solution; Cr absorption was suppressed indicating that there are nutrient(s) of the TCM which facilitate Cr absorption. Further suppression occurred when a Cr concentration gradient opposing Cr absorption was created (IP at 100 ppb Cr, VP at 400 ppb Cr).

  17. In vivo studies of biotin absorption in distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  18. Intestinal scavenger receptors are involved in vitamin K1 absorption.

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-10-31

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone.

  19. Intestinal Scavenger Receptors Are Involved in Vitamin K1 Absorption*

    PubMed Central

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-01-01

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone. PMID:25228690

  20. Can lipid nanoparticles improve intestinal absorption?

    PubMed

    Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

    2016-12-30

    Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs.

  1. Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

    PubMed Central

    Ruiz-Balaguer, N; Nacher, A; Casabo, V G; Merino, M

    1997-01-01

    Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site. PMID:9021205

  2. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters

    PubMed Central

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-01

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na+/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca2+]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca2+ in IEC are regulated by cation channels and transporters, such as Ca2+ channels, K+ channels, Na+/Ca2+ exchangers, and Na+/H+ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes. PMID:26784222

  3. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters.

    PubMed

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-14

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na⁺/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca(2+)]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K⁺ channels, Na⁺/Ca(2+) exchangers, and Na⁺/H⁺ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.

  4. Regulation of intestinal lipid absorption by clock genes.

    PubMed

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

  5. Contribution of dietary oxalate to urinary oxalate excretion

    NASA Technical Reports Server (NTRS)

    Holmes, R. P.; Goodman, H. O.; Assimos, D. G.

    2001-01-01

    BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

  6. Response to Dietary Oxalate after Bariatric Surgery

    PubMed Central

    Froeder, Leila; Arasaki, Carlos Haruo; Malheiros, Carlos Alberto; Baxmann, Alessandra Calábria

    2012-01-01

    Summary Background and objectives Bariatric surgery (BS) may be associated with increased oxalate excretion and a higher risk of nephrolithiasis. This study aimed to investigate urinary abnormalities and responses to an acute oxalate load as an indirect assessment of the intestinal absorption of oxalate in this population. Design, setting, participants, & measurements Twenty-four–hour urine specimens were collected from 61 patients a median of 48 months after BS (post-BS) as well as from 30 morbidly obese (MO) participants; dietary information was obtained through 24-hour food recalls. An oral oxalate load test (OLT), consisting of 2-hour urine samples after overnight fasting and 2, 4, and 6 hours after consuming 375 mg of oxalate (spinach juice), was performed on 21 MO and 22 post-BS patients 12 months after BS. Ten post-BS patients also underwent OLT before surgery (pre-BS). Results There was a higher percentage of low urinary volume (<1.5 L/d) in post-BS versus MO (P<0.001). Hypocitraturia and hyperoxaluria (P=0.13 and P=0.36, respectively) were more frequent in BS versus MO patients. The OLT showed intragroup (P<0.001 for all periods versus baseline) and intergroup differences (P<0.001 for post-BS versus MO; P=0.03for post-BS versus pre-BS). The total mean increment in oxaluria after 6 hours of load, expressed as area under the curve, was higher in both post-BS versus MO and in post-BS versus pre-BS participants (P<0.001 for both). Conclusions The mean oxaluric response to an oxalate load is markedly elevated in post-bariatric surgery patients, suggesting that increased intestinal absorption of dietary oxalate is a predisposing mechanism for enteric hyperoxaluria. PMID:23024163

  7. The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.

    PubMed

    Fuqua, Brie K; Lu, Yan; Darshan, Deepak; Frazer, David M; Wilkins, Sarah J; Wolkow, Natalie; Bell, Austin G; Hsu, JoAnn; Yu, Catherine C; Chen, Huijun; Dunaief, Joshua L; Anderson, Gregory J; Vulpe, Chris D

    2014-01-01

    Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex-linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia mice still retain some hephaestin ferroxidase activity. They survive, breed, and their anemia improves with age. To gain a better understanding of the role of hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout mouse models with whole body or intestine-specific (Villin promoter) ablation of hephaestin. Both types of mice were viable, indicating that hephaestin is not essential and that other mechanisms, multicopper ferroxidase-dependent or not, must compensate for hephaestin deficiency. The knockout strains, however, both developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition. Consistent with this, the knockout mice accumulated iron in duodenal enterocytes and had reduced intestinal iron absorption. In addition, the similarities of the phenotypes of the whole body and intestine-specific hephaestin knockout mice clarify the important role of hephaestin specifically in intestinal enterocytes in maintaining whole body iron homeostasis. These mouse models will serve as valuable tools to study the role of hephaestin and associated proteins in iron transport in the small intestine and other tissues.

  8. The Multicopper Ferroxidase Hephaestin Enhances Intestinal Iron Absorption in Mice

    PubMed Central

    Fuqua, Brie K.; Lu, Yan; Darshan, Deepak; Frazer, David M.; Wilkins, Sarah J.; Wolkow, Natalie; Bell, Austin G.; Hsu, JoAnn; Yu, Catherine C.; Chen, Huijun; Dunaief, Joshua L.; Anderson, Gregory J.; Vulpe, Chris D.

    2014-01-01

    Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex-linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia mice still retain some hephaestin ferroxidase activity. They survive, breed, and their anemia improves with age. To gain a better understanding of the role of hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout mouse models with whole body or intestine-specific (Villin promoter) ablation of hephaestin. Both types of mice were viable, indicating that hephaestin is not essential and that other mechanisms, multicopper ferroxidase-dependent or not, must compensate for hephaestin deficiency. The knockout strains, however, both developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition. Consistent with this, the knockout mice accumulated iron in duodenal enterocytes and had reduced intestinal iron absorption. In addition, the similarities of the phenotypes of the whole body and intestine-specific hephaestin knockout mice clarify the important role of hephaestin specifically in intestinal enterocytes in maintaining whole body iron homeostasis. These mouse models will serve as valuable tools to study the role of hephaestin and associated proteins in iron transport in the small intestine and other tissues. PMID:24896847

  9. Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

    PubMed Central

    Keating, J; Bjarnason, I; Somasundaram, S; Macpherson, A; Francis, N; Price, A B; Sharpstone, D; Smithson, J; Menzies, I S; Gazzard, B G

    1995-01-01

    Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes. PMID:8549936

  10. Activation of rat intestinal mucosal mast cells by fat absorption.

    PubMed

    Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-06-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent.

  11. Defective intestinal amino acid absorption in Ace2 null mice.

    PubMed

    Singer, Dustin; Camargo, Simone M R; Ramadan, Tamara; Schäfer, Matthias; Mariotta, Luca; Herzog, Brigitte; Huggel, Katja; Wolfer, David; Werner, Sabine; Penninger, Josef M; Verrey, François

    2012-09-15

    Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations.

  12. Analysis of sequential events in intestinal absorption of folylpolyglutamate

    SciTech Connect

    Darcy-Vrillon, B.; Selhub, J.; Rosenberg, I.H.

    1988-09-01

    Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of ''natural'' folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.

  13. Variability of bioavailability and intestinal absorption mechanisms of metoprolol.

    PubMed

    Fukao, Miki; Ishida, Kazuya; Horie, Asuka; Taguchi, Masato; Nozawa, Takashi; Inoue, Hiroshi; Hashimoto, Yukiya

    2014-01-01

    We previously reported that aging and/or cytochrome P450 2D6 polymorphism are responsible for the interindividual variability in the systemic clearance (CL) and bioavailability (F) of metoprolol. The aim of the present study was to evaluate the residual variability of F of metoprolol in routinely treated Japanese patients and to investigate the intestinal absorption mechanism of the drug using human intestinal epithelial LS180 cells. We first re-analyzed the blood concentration data for metoprolol in 34 Japanese patients using a nonlinear mixed effects model. The oral clearance (CL/F) of metoprolol was positively correlated with the apparent volume of distribution (V/F), suggesting the residual variability of F. The uptake of metoprolol into LS180 cells was significantly decreased by the acidification of extracellular medium pH, and was dependent on temperature and intracellular pH. Furthermore, the cellular uptake of metoprolol was saturable, and was significantly decreased in the presence of hydrophobic cationic drugs such as diphenhydramine, procainamide, bisoprolol, and quinidine. These findings indicate that residual variability of F is one of the causes of the interindividual pharmacokinetic variability of metoprolol, and that the interindividual variability of not only presystemic first-pass metabolism, but also intestinal absorption, may be responsible for the variable F of the drug.

  14. Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

    PubMed

    Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2011-01-05

    Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

  15. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  16. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability.

    PubMed

    Wen, Xia; Walle, Thomas

    2006-10-01

    To better understand the relationship between the chemical structure and biological fate of dietary polyphenols, the hepatic metabolic stability and intestinal absorption of methylated polyphenols, in comparison with unmethylated polyphenols, were investigated in pooled human liver S9 fraction and human colon adenocarcinoma (Caco-2) cells. Consistent with previous in vivo studies, the two well known unmethylated polyphenols resveratrol (3,5,4'-trihydroxystilbene) and quercetin (3,5,7,3',4'-pentahydroxyflavone) were rapidly eliminated by the S9 fraction in the presence of the appropriate cofactors for conjugation and oxidation. In contrast, the methylated flavones, i.e., 7-methoxyflavone, 7,4'-dimethoxyflavone, 5,7-dimethoxyflavone, and 5,7,4'-trimethoxyflavone, were relatively stable, indicating high resistance to hepatic metabolism. The corresponding unmethylated flavones, i.e., 7-hydroxyflavone, 7,4'-dihydroxyflavone, chrysin (5,7-dihydroxyflavone), and apigenin (5,7,4'-trihydroxyflavone), were rapidly eliminated because of extensive glucuronidation and/or sulfation just as resveratrol and quercetin were. The rate of intestinal absorption was evaluated using Caco-2 cells grown in porous inserts. The methylated flavones showed approximately 5- to 8-fold higher apparent permeability (P(app), 22.6-27.6 x 10(-6) cm s(-1)) of apical to basolateral flux than the unmethylated flavones (P(app), 3.0-7.8 x 10(-6) cm s(-1)). The lower P(app) values for the unmethylated flavones correlated with their extensive metabolism in the Caco-2 cells. Thus, combined use of the hepatic S9 fraction and Caco-2 cells will be useful for predicting the oral bioavailability of dietary polyphenols. The higher hepatic metabolic stability and intestinal absorption of the methylated polyphenols make them more favorable than the unmethylated polyphenols to be developed as potential cancer chemopreventive agents.

  17. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    NASA Technical Reports Server (NTRS)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  18. Effect of Diet upon Intestinal Disaccharidases and Disaccharide Absorption*

    PubMed Central

    Deren, J. J.; Broitman, S. A.; Zamcheck, N.

    1967-01-01

    The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal. Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats. PMID:6018758

  19. Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues.

    PubMed

    Miyake, Masateru; Toguchi, Hajime; Nishibayashi, Toru; Higaki, Kazutaka; Sugita, Akira; Koganei, Kazutaka; Kamada, Nobuhiko; Kitazume, Mina T; Hisamatsu, Tadakazu; Sato, Toshiro; Okamoto, Susumu; Kanai, Takanori; Hibi, Toshifumi

    2013-08-01

    The objective of this study was to establish a novel prediction system of drug absorption in humans by utilizing human intestinal tissues. Based on the transport index (TI), a newly defined parameter, calculated by taking account of the change in drug concentrations because of precipitation on the apical side and the amounts accumulated in the tissue and transported to the basal side, the absorbability of drugs in rank order as well as the fraction of dose absorbed (Fa) in humans were estimated. Human intestinal tissues taken from ulcerative colitis or Crohn's disease patients were mounted in a mini-Ussing chamber and transport studies were performed to evaluate the permeation of drugs, including FD-4, a very low permeable marker, atenolol, a low permeable marker, and metoprolol, a high permeable marker. Although apparent permeability coefficients calculated by the conventional equation did not reflect human Fa values for FD-4, atenolol, and metoprolol, TI values were well correlated with Fa values, which are described by 100 · [1 - e (- f · (TI - α)) ]. Based on this equation, Fa values in humans for other test drugs were predicted successfully, indicating that our new system utilizing human intestinal tissues would be valuable for predicting oral drug absorption in humans.

  20. Intestinal Water Absorption Varies with Expected Dietary Water Load among Bats but Does Not Drive Paracellular Nutrient Absorption.

    PubMed

    Price, Edwin R; Brun, Antonio; Gontero-Fourcade, Manuel; Fernández-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2015-01-01

    Rapid absorption and elimination of dietary water should be particularly important to flying species and were predicted to vary with the water content of the natural diet. Additionally, high water absorption capacity was predicted to be associated with high paracellular nutrient absorption due to solvent drag. We compared the water absorption rates of sanguivorous, nectarivorous, frugivorous, and insectivorous bats in intestinal luminal perfusions. High water absorption rates were associated with high expected dietary water load but were not highly correlated with previously measured rates of (paracellular) arabinose clearance. In conjunction with these tests, we measured water absorption and the paracellular absorption of nutrients in the intestine and stomach of vampire bats using luminal perfusions to test the hypothesis that the unique elongated vampire stomach is a critical site of water absorption. Vampire bats' gastric water absorption was high compared to mice but not compared to their intestines. We therefore conclude that (1) dietary water content has influenced the evolution of intestinal water absorption capacity in bats, (2) solvent drag is not the only driver of paracellular nutrient absorption, and (3) the vampire stomach is a capable but not critical location for water absorption.

  1. Oxalate: Effect on calcium absorbability

    SciTech Connect

    Heaney, R.P.; Weaver, C.M. )

    1989-10-01

    Absorption of calcium from intrinsically labeled Ca oxalate was measured in 18 normal women and compared with absorption of Ca from milk in these same subjects, both when the test substances were ingested in separate meals and when ingested together. Fractional Ca absorption from oxalate averaged 0.100 +/- 0.043 when ingested alone and 0.140 +/- 0.063 when ingested together with milk. Absorption was, as expected, substantially lower than absorption from milk (0.358 +/- 0.113). Nevertheless Ca oxalate absorbability in these women was higher than we had previously found for spinach Ca. When milk and Ca oxalate were ingested together, there was no interference of oxalate in milk Ca absorption and no evidence of tracer exchange between the two labeled Ca species.

  2. Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.

    PubMed

    Zhang, Hailong; Mi, Jie; Huo, Yayu; Huang, Xiaoyan; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2014-05-15

    Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.

  3. Extra-intestinal calcium handling contributes to normal serum calcium levels when intestinal calcium absorption is suboptimal.

    PubMed

    Lieben, Liesbet; Verlinden, Lieve; Masuyama, Ritsuko; Torrekens, Sophie; Moermans, Karen; Schoonjans, Luc; Carmeliet, Peter; Carmeliet, Geert

    2015-12-01

    The active form of vitamin D, 1,25(OH)2D, is a crucial regulator of calcium homeostasis, especially through stimulation of intestinal calcium transport. Lack of intestinal vitamin D receptor (VDR) signaling does however not result in hypocalcemia, because the increased 1,25(OH)2D levels stimulate calcium handling in extra-intestinal tissues. Systemic VDR deficiency, on the other hand, results in hypocalcemia because calcium handling is impaired not only in the intestine, but also in kidney and bone. It remains however unclear whether low intestinal VDR activity, as observed during aging, is sufficient for intestinal calcium transport and for mineral and bone homeostasis. To this end, we generated mice that expressed the Vdr exclusively in the gut, but at reduced levels. We found that ~15% of intestinal VDR expression greatly prevented the Vdr null phenotype in young-adult mice, including the severe hypocalcemia. Serum calcium levels were, however, in the low-normal range, which may be due to the suboptimal intestinal calcium absorption, renal calcium loss, insufficient increase in bone resorption and normal calcium incorporation in the bone matrix. In conclusion, our results indicate that low intestinal VDR levels improve intestinal calcium absorption compared to Vdr null mice, but also show that 1,25(OH)2D-mediated fine-tuning of renal calcium reabsorption and bone mineralization and resorption is required to maintain fully normal serum calcium levels.

  4. Intestinal absorption of calcium from calcium ascorbate in rats.

    PubMed

    Tsugawa, N; Yamabe, T; Takeuchi, A; Kamao, M; Nakagawa, K; Nishijima, K; Okano, T

    1999-01-01

    The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

  5. Factors affecting intestinal absorption of cholesterol and plant sterols and stanols.

    PubMed

    Ikeda, Ikuo

    2015-01-01

    Various factors affect intestinal absorption of cholesterol and plant sterols and stanols. Plant sterols and stanols are generally less absorptive than cholesterol. Differential absorption rates among various plant sterols and stanols have been also reported. Although it was suggested that differential absorption among cholesterol and various plant sterols was determined by difference in excretion rates of sterols and stanols through ATP-binding cassette transporter (ABC) G5/ABCG8 of intestinal cells, our study suggests that affinity for and solubility in bile salt micelles can be important determinants for differential absorption of plant sterols and stanols. It was also suggested that plant sterols were transiently incorporated into intestinal cells and then excreted to intestinal lumen through ABCG5/ABCG8. However, in a rat study, transient incorporation of sitosterol into intestinal cells was not observed, suggesting that sitosterol is differentiated from cholesterol at the incorporation site of intestinal cells. It is well established that plant sterols inhibit intestinal absorption of cholesterol and exert a hypocholesterolemic activity. Plant sterols are solubilized in bile salt micelles as cholesterol. Our study clearly showed that because the sterol-solubilizing capacity of bile salt micelles was limited, plant sterols solubilized in micelles reduced the solubility of cholesterol. This can be the major cause of inhibition of cholesterol absorption by plant sterols. Pancreatic cholesterol esterase accelerates intestinal absorption of unesterified cholesterol. Although it was suggested that cholesterol esterase accelerated esterification of cholesterol incorporated into intestinal cells and acted as a transporter at the surface of intestinal cells, our research revealed that the accelerated cholesterol absorption was caused by hydrolysis of phosphatidylcholine in bile salt micelles. It is thought that hydrolysis of phosphatidylcholine reduces the affinity of

  6. Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

    PubMed

    Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

    2013-12-01

    The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress.

  7. Effects of xylitol on the absorption of /sup 203/Pb in mice and cockerels

    SciTech Connect

    Mykkaenen, H.M.; Salminen, S.J.

    1986-07-01

    Earlier studies have indicated that xylitol may increase the absorption and urinary excretion of dietary oxalate. It has also been indicated that xylitol increases the absorption of calcium. Intestinal absorption of lead, a divalent contaminant in the diet, is in many respects similar to that of calcium. The purpose of this study was to evaluate the effects of xylitol on the intestinal absorption of lead using two different approaches: the in situ ligated intestinal loop technique in cockerels and gastric gavage in mice.

  8. [Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations].

    PubMed

    Liu, Ying; Yi, Tao; Di, Huan; Xiao, Lu; He, Ji-Kui

    2011-08-01

    A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.

  9. Lithocholic acid: a new emergent protector of intestinal calcium absorption under oxidant conditions.

    PubMed

    Marchionatti, Ana M; Pérez, Adriana; Rivoira, María A; Rodríguez, Valeria A; Tolosa de Talamoni, Nori G

    2017-04-01

    LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secosteroid stimulates intestinal Ca(2+) absorption. Whether LCA alters this process remains unknown. The aim of our work was to determine the effect of LCA on intestinal Ca(2+) absorption in the absence or presence of NaDOC, bile acid that inhibits the cation transport. The data show that LCA by itself did not alter intestinal Ca(2+) absorption, but prevented the inhibitory effect of NaDOC. The concomitant administration of LCA avoided the reduction of intestinal alkaline phosphatase activity caused by NaDOC. In addition, LCA blocked a decrease caused by NaDOC on gene and protein expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption. The oxidative stress and apoptosis triggered by NaDOC were abrogated by LCA co-treatment. In conclusion, LCA placed in the intestinal lumen protects intestinal Ca(2+) absorption against the inhibitory effects caused by NaDOC. LCA avoids the reduction of the transcellular Ca(2+) movement, apparently by blocking the oxidative stress and apoptosis triggered by NaDOC, normalizing the gene and protein expression of molecules involved in Ca(2+) movement. Therefore, LCA might become a possible treatment to improve intestinal calcium absorption under oxidant conditions.

  10. Mathematical Modeling of Intestinal Iron Absorption Using Genetic Programming

    PubMed Central

    Colins, Andrea; Gerdtzen, Ziomara P.; Nuñez, Marco T.; Salgado, J. Cristian

    2017-01-01

    Iron is a trace metal, key for the development of living organisms. Its absorption process is complex and highly regulated at the transcriptional, translational and systemic levels. Recently, the internalization of the DMT1 transporter has been proposed as an additional regulatory mechanism at the intestinal level, associated to the mucosal block phenomenon. The short-term effect of iron exposure in apical uptake and initial absorption rates was studied in Caco-2 cells at different apical iron concentrations, using both an experimental approach and a mathematical modeling framework. This is the first report of short-term studies for this system. A non-linear behavior in the apical uptake dynamics was observed, which does not follow the classic saturation dynamics of traditional biochemical models. We propose a method for developing mathematical models for complex systems, based on a genetic programming algorithm. The algorithm is aimed at obtaining models with a high predictive capacity, and considers an additional parameter fitting stage and an additional Jackknife stage for estimating the generalization error. We developed a model for the iron uptake system with a higher predictive capacity than classic biochemical models. This was observed both with the apical uptake dataset used for generating the model and with an independent initial rates dataset used to test the predictive capacity of the model. The model obtained is a function of time and the initial apical iron concentration, with a linear component that captures the global tendency of the system, and a non-linear component that can be associated to the movement of DMT1 transporters. The model presented in this paper allows the detailed analysis, interpretation of experimental data, and identification of key relevant components for this complex biological process. This general method holds great potential for application to the elucidation of biological mechanisms and their key components in other complex

  11. Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography.

    PubMed

    Waters, Laura J; Shokry, Dina S; Parkes, Gareth M B

    2016-10-01

    Understanding intestinal absorption for pharmaceutical compounds is vital to estimate the bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems; however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition-absorption relationship. MLC offers many benefits including environmental, economic, time-saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Human intestinal absorption--neutral molecules and ionic species.

    PubMed

    Abraham, Michael H

    2014-07-01

    Analysis of percentage human intestinal absorption (%HIA) for 280 drugs shows that an excellent fit can be obtained using only three descriptors for neutral molecules with a SD of 13.9%. Use of descriptors for individual cations and anions does not lead to any better goodness-of-fit. It is noted that diffusion coefficients in water for ionized molecules are almost identical to those for the corresponding neutral molecules. Comparison of equation coefficients for HIA with those for other processes shows that HIA resembles diffusion in water but does not resemble permeation through biological bilayers. It is shown that compound substituent effects on HIA are near those for diffusion but are far away from substituent effects on permeation through a typical bilayer. Calculations indicate that rates of permeation through an unstirred mucosal layer are of the same order as experimental rates of permeation in HIA. It is concluded that for the 280 compound set, diffusion through the unstirred mucosal layer is the rate determining step. The effect on pK(a) in transfer of acids and bases from water to another solvent, and of diffusion past a negative charge in a phase/bilayer is also considered.

  13. Pinoresinol of olive oil decreases vitamin D intestinal absorption.

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Tagliaferri, Camille; Lebecque, Patrice; Georgé, Stéphane; Wittrant, Yohann; Coxam, Véronique; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2016-09-01

    Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D.

  14. Update: The Digestion and Absorption of Carbohydrate and Protein: Role of the Small Intestine.

    ERIC Educational Resources Information Center

    Leese, H. J.

    1984-01-01

    Discusses the role of the small intestine in the digestion and absorption of carbohydrates and proteins. Indicates as outdated the view that these materials must be broken down to monomeric units before absorption and that the gut secretes a mixture of digestive juices which brings about absorption. (JN)

  15. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs

    PubMed Central

    Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

    2016-01-01

    With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs. PMID:27455239

  16. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs.

    PubMed

    Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

    2016-07-21

    With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs.

  17. Mechanisms of intestinal absorption of the carcinogen MNNG (N-Methyl-N'-nitro-N-nitrosoguanidine)

    SciTech Connect

    Koyama, S.Y.; Hollander, D.; Dadufalza, V.

    1988-06-01

    The authors 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 rat in vivo in male Sprague-Dawley rats. They 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 ..mu..g/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.

  18. Intestinal ferritin H is required for an accurate control of iron absorption.

    PubMed

    Vanoaica, Liviu; Darshan, Deepak; Richman, Larry; Schümann, Klaus; Kühn, Lukas C

    2010-09-08

    To maintain appropriate body iron levels, iron absorption by the proximal duodenum is thought to be controlled by hepcidin, a polypeptide secreted by hepatocytes in response to high serum iron. Hepcidin limits basolateral iron efflux from the duodenal epithelium by binding and downregulating the intestinal iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H gene deletion show increased body iron stores and transferrin saturation. As expected for iron-loaded animals, the ferritin H-deleted mice showed induced liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB mRNA. In spite of these feedback controls, intestinal ferroportin protein and (59)Fe absorption were increased more than 2-fold in the deleted mice. Our results demonstrate that hepcidin-mediated regulation alone is insufficient to restrict iron absorption and that intestinal ferritin H is also required to limit iron efflux from intestinal cells.

  19. Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and effect of NSAIDs.

    PubMed

    Yokooji, Tomoharu; Hamura, Koh; Matsuo, Hiroaki

    2013-08-16

    The absorption pathway(s) of a representative food allergen, lysozyme, and the mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory drugs were examined by intestinal closed-loop and re-circulating perfusion methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled lysozyme in the proximal intestine was higher than that for a marker of non-specific absorption, FD-10, and was suppressed by colchicine (endocytosis inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal intestine with no effects on tissue accumulation. Diclofenac facilitated FITC-lysozyme absorption, but meloxicam and loxoprofen exerted no effects on absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog) with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC-lysozyme to the same level as that seen with controls. Thus, lysozyme absorption was mediated by endocytic and paracellular pathways in the proximal intestine, and was facilitated by aspirin and diclofenac after impairment of the paracellular pathway. Misoprostol may suppress the allergen absorption facilitated by aspirin.

  20. [Improvement of intestinal absorption of poorly absorbable drugs by various sugar esters].

    PubMed

    Yamamoto, Akira; Katsumi, Hidemasa; Kusamori, Kosuke; Sakane, Toshiyasu

    2014-01-01

    Effects of sucrose fatty acid esters (sugar esters) on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption of CF from the rat small intestine was significantly enhanced in the presence of various sugar esters and a maximal absorption enhancing effect was observed in the presence of 0.5%(w/v) S-1670. The absorption enhancing effect of S-1670 in the small intestine decreased as the molecular weights of drugs increased. Moreover, we evaluated the intestinal membrane damage with or without various sugar esters. These sugar esters (0.5%(w/v)) did not increase the activities of lactate dehydrogenase (LDH), suggesting that these sugar esters did not cause serious membrane damage to the intestinal epithelium. Furthermore, these sugar esters increased membrane fluidity of lipid layers of the intestinal brush border membranes and decreased the transepithelial electrical resistance (TEER) of Caco-2 cells. Therefore, these findings suggested that these sugar esters might improve the intestinal absorption of poorly absorbable drugs via a transcellular and a paracellular pathways.

  1. Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption.

    PubMed

    Choi, Pamela M; Guo, Jun; Erwin, Christopher R; Wandu, Wambui S; Leinicke, Jennifer A; Xie, Yan; Davidson, Nicholas O; Warner, Brad W

    2014-05-15

    We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO). Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR). Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO) along with their floxed (wild-type, WT) littermates were placed on a high-fat diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption.

  2. Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption

    PubMed Central

    Choi, Pamela M.; Guo, Jun; Erwin, Christopher R.; Wandu, Wambui S.; Leinicke, Jennifer A.; Xie, Yan; Davidson, Nicholas O.

    2014-01-01

    We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO). Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR). Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO) along with their floxed (wild-type, WT) littermates were placed on a high-fat diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption. PMID:24742992

  3. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.

  4. An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption.

    PubMed

    Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung-Junn; Chan, Lawrence; Schwartz, Gary J; Chua, Streamson C; Hussain, M Mahmood

    2010-07-01

    Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

  5. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications.

    PubMed

    Cohn, Jeffrey S; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W S; Tandy, Sally

    2010-06-01

    A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals.

  6. Acute oxalate nephropathy associated with orlistat

    PubMed Central

    Humayun, Youshay; Ball, Kenneth C.; Lewin, Jack R.; Lerant, Anna A.; Fülöp, Tibor

    2016-01-01

    Background: Obesity is a major world-wide epidemic which has led to a surge of various weight loss-inducing medical or surgical treatments. Orlistat is a gastrointestinal lipase inhibitor used as an adjunct treatment of obesity and type 2 diabetes mellitus to induce clinically significant weight loss via fat malabsorption. Case Presentation: We describe a case of a 76-year-old female with past medical history of chronic kidney disease (baseline serum creatinine was 1.5-2.5 mg/dL), hypertension, gout and psoriatic arthritis, who was admitted for evaluation of elevated creatinine, peaking at 5.40 mg/dL. She was started on orlistat 120 mg three times a day six weeks earlier. Initial serologic work-up remained unremarkable. Percutaneous kidney biopsy revealed massive calcium oxalate crystal depositions with acute tubular necrosis and interstitial inflammation. Serum oxalate level returned elevated at 45 mm/l (normal <27). Timed 24-hour urine collection documented increased oxalate excretion repeatedly (54-96 mg/24 hour). After five renal dialysis sessions in eighth days she gradually regained her former baseline kidney function with creatinine around 2 mg/dL. Given coexisting proton-pump inhibitor therapy, only per os calcium-citrate provided effective intestinal oxalate chelation to control hyperoxaluria. Conclusions: Our case underscores the potential of medically induced fat malabsorption to lead to an excessive oxalate absorption and acute kidney injury (AKI), especially in subjects with pre-existing renal impairment. Further, it emphasizes the importance of kidney biopsy to facilitate early diagnosis and treatment. PMID:27152294

  7. Intestinal absorption of vitamin D: from the meal to the enterocyte.

    PubMed

    Reboul, Emmanuelle

    2015-02-01

    Vitamin D plays key roles in bone, infectious, inflammatory and metabolic diseases. As most people get inadequate sun exposure for sufficient vitamin D status, they need adequate intake of dietary vitamin D. Many studies see optimizing vitamin D status as a public health priority. It is thus vital to gain deeper insight into vitamin D intestinal absorption. It was long assumed that vitamin D intestinal absorption is a passive process, but new data from our laboratory showed that it is actually far more complex than previously thought. This review describes the fate of vitamin D in the human upper gastrointestinal lumen during digestion and focuses on the proteins involved in the intestinal membrane and cellular transport of vitamin D across the enterocyte. Although recent data significantly improve our understanding of vitamin D intestinal absorption, further studies are still needed to increase our knowledge of the molecular mechanisms underlying this phenomenon.

  8. Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

    PubMed Central

    Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

    2001-01-01

    AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

  9. New insights into the molecular mechanism of intestinal fatty acid absorption

    PubMed Central

    Wang, Tony Y.; Liu, Min; Portincasa, Piero; Wang, David Q.-H.

    2013-01-01

    Background Dietary fat is the most important energy source of all the nutrients. Fatty acids, stored as triacylglycerols in the body, are an important reservoir of stored energy and derive primarily from animal fats and vegetable oils. Design Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, i.e., fatty acid transporters on the apical membrane of enterocytes. Results These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical-chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. Conclusions A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. PMID:24102389

  10. [Absorption of flavonoids from Abelmoschus manihot extract by in situ intestinal perfusion].

    PubMed

    Xue, Cai-fu; Guo, Jian-ming; Qian, Da-wei; Duan, Jin-ao; Shu, Yan

    2011-04-01

    To explore the mechanism of the absorption of flavonoids from Abelmoschus manihot flowers, in situ intestinal recirculation was performed to study the effect of the absorption at different concentrations and different intestinal regions. To evaluate the conditions of the absorption of six flavonoids from Abelmoschus manihot flowers, the concentrations of Abelmoschus manihot in the perfusion solution were determined by HPLC at predesigned time. And we have investigated the inhibitory effect of six flavonoids from Abelmoschus manihot flowers on P-glycoprotein (P-gp) drug efflux pump. The results demonstrated that the absorption rates of flavonoids from Abelmoschus manihot flowers are not significantly different (P > 0.05) at various drug concentrations, the absorption of flavonoids from Abelmoschus manihot flowers is a first-order process with the passive diffusion mechanism. The absorption rates of each of flavonoids are significantly different. The absorption rate of flavonoid glycoside was lower than that of aglycone; the flavonoids from Abelmoschus manihot flowers could be absorbed in all of the intestinal segments. The best parts of intestine to absorb hyperoside and myricetin are jejunum and duodenum, separately. Verapamil could enhance the absorption of isoquercitrin, hyperoside, myricetin and quercetin-3'-O-glucoside by inhibiting P-glycoprotein (P-gp) drug efflux pump.

  11. Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice.

    PubMed

    Shim, Jien; Moulson, Casey L; Newberry, Elizabeth P; Lin, Meei-Hua; Xie, Yan; Kennedy, Susan M; Miner, Jeffrey H; Davidson, Nicholas O

    2009-03-01

    FA transport protein 4 (FATP4), one member of a multigene family of FA transporters, was proposed as a major FA transporter in intestinal lipid absorption. Due to the fact that Fatp4(-/-) mice die because of a perinatal skin defect, we rescued the skin phenotype using an FATP4 transgene driven by a keratinocyte-specific promoter (Fatp4(-/-);Ivl-Fatp4(tg/+) mice) to elucidate the role of intestinal FATP4 in dietary lipid absorption. Fatp4(-/-);Ivl-Fatp4(tg/+) mice and wild-type littermates displayed indistinguishable food consumption, growth, and weight gain on either low or high fat (Western) diets, with no differences in intestinal triglyceride (TG) absorption or fecal fat losses. Cholesterol absorption and intestinal TG absorption kinetics were indistinguishable between the genotypes, although Western diet fed Fatp4(-/-);Ivl-Fatp4(tg/+) mice showed a significant increase in enterocyte TG and FA content. There was no compensatory upregulation of other FATP family members or any other FA or cholesterol transporters in Fatp4(-/-);Ivl-Fatp4(tg/+) mice. Furthermore, although serum cholesterol levels were lower in Fatp4(-/-);Ivl-Fatp4(tg/+) mice, there was no difference in hepatic VLDL secretion in-vivo or in hepatic lipid content on either a chow or Western diet. Taken together, our studies find no evidence for a physiological role of intestinal FATP4 in dietary lipid absorption in mice.

  12. Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.

    PubMed

    Aspenström-Fagerlund, Bitte; Tallkvist, Jonas; Ilbäck, Nils-Gunnar; Glynn, Anders W

    2015-09-02

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  13. [Effect of various coumarins on the intestinal absorption of galactose in vivo (author's transl)].

    PubMed

    Ruano, M J; Bolufer, J; Larralde, J; Lluch, M

    1975-06-01

    The effect of various coumarins on the active transport of galactose by small intestine in chick and rat was studied, using the in vivo technique of sucessive absorptions. A 10(-4) M concentration of the different coumarins inhibits the absorption of galactose in the chick. This effect persists in successive absorptions without coumarin. In rat, inhibition of galactose active transport by coumarins was observed at 10(-3) M concentration.

  14. Intestinal absorption and histomorphometry of Syrian hamsters (Mesocricetus auratus) experimentally infected with Lawsonia intracellularis.

    PubMed

    Vannucci, Fabio Augusto; Borges, Elizabeth Lage; de Oliveira, Juliana Saes Vilaça; Guedes, Roberto Mauricio Carvalho

    2010-10-26

    The objective of this study was to evaluate the intestinal absorption and histomorphometry of hamsters experimentally infected with Lawsonia intracellularis and correlate these parameters with severity of infection based on immunohistochemistry. Sixty hamsters were equally divided into control and inoculated groups which were orally infected with intestinal mucosa homogenate from pigs naturally infected with L. intracellularis. The intestinal absorption of glucose, sodium, potassium and chloride was evaluated in live animals (25 inoculated and 25 control) on day 26 after inoculation. In this procedure, a standard solution was infused into the cranial jejunum and collected at the terminal ileum. The experimental infection was confirmed by gross and histopathological examination and L. intracellularis antigen labeling by immunohistochemistry. Histomorphometry analysis demonstrated positive correlation between intestinal crypt depth and severity of infection based on immunohistochemistry. Infected animals had significantly lower intestinal absorption of glucose, potassium and chloride. These results indicate a lower intestinal absorption as an important mechanism of diarrhea in hamsters experimentally infected with L. intracellularis. Therefore, malabsorption should be considered as the main mechanism involved in the physiopathology of the diarrhea in L. intracellularis infected animals.

  15. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection

    PubMed Central

    Jeppesen, P; Staun, M; Tjellesen, L; Mortensen, P

    1998-01-01

    Background—H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. 
Aims—To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. 
Methods—Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100cm were studied. Omeprazole 40 mg twice daily or ranitidine 150mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. 
Results—Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1−2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12-15 months, but none could be weaned from parenteral nutrition. 
Conclusion—Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low. 

 Keywords: short bowel syndrome; human; diarrhoea; ranitidine; omeprazole PMID:9824602

  16. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    PubMed

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium.

  17. Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin.

    PubMed

    Togami, Kohei; Hayashi, Yoshiaki; Chono, Sumio; Morimoto, Kazuhiro

    2014-09-01

    The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration-time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3- and 1.6-fold, respectively, after concomitant oral administration of verapamil as a P-glycoprotein (P-gp) inhibitor. Further, an in vitro transport experiment was performed using Caco-2 cell monolayers as a model of intestinal epithelial cells. The apical-to-basolateral transport of CAM and TEL through the Caco-2 cell monolayers was lower than their basolateral-to-apical transport. Verapamil and bromosulfophthalein as a multidrug resistance-associated proteins (MRPs) inhibitor significantly increased the apical-to-basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P-gp and MRPs on the intestinal epithelial cells.

  18. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (-)-epigallocatechin gallate.

    PubMed

    Dube, Admire; Nicolazzo, Joseph A; Larson, Ian

    2010-10-09

    Catechins found in green tea have received considerable attention due to their favourable biological properties which include cardioprotective, neuroprotective and anti-cancer effects. However, their therapeutic potential is limited by their low oral bioavailability, attributed to poor stability and intestinal absorption. We encapsulated (+)-catechin (C) and (-)-epigallocatechin gallate (EGCg) in chitosan nanoparticles (CS NP) as a means of enhancing their intestinal absorption. Using excised mouse jejunum in Ussing chambers, encapsulation significantly enhanced (p<0.05) intestinal absorption. The cumulative amounts transported after encapsulation were significantly higher (p<0.05), i.e. 302.1+/-46.1 vs 206.8+/-12.6ng/cm(2) and 102.7+/-12.4 vs 57.9+/-7.9ng/cm(2) for C and EGCg, respectively. The mechanism by which absorption was enhanced was not through an effect of CS NPs on intestinal paracellular or passive transcellular transport processes (as shown by transport of (14)C-mannitol and (3)H-propranolol) or an effect on efflux proteins (as shown by transport of (3)H-digoxin) but was likely due to stabilization of catechins after encapsulation (99.7+/-0.7 vs 94.9+/-3.8% and 56.9+/-3.0 vs 1.3+/-1.7% of the initial C and EGCg concentration remaining, respectively). This study demonstrates that encapsulation of catechins in CS NPs enhances their intestinal absorption and is a promising strategy for improving their bioavailability.

  19. [Rat intestinal absorption trait of peimine and peiminine in Thunberg fritillary bulb extract].

    PubMed

    Guan, Zhi-Yu; Zhang, Li-Hua; Chen, Li-Hua; Zhu, Wei-Feng; Liu, Hong-Ning

    2013-12-01

    To study the in situ intestinal absorption kinetics and compatibility influence of peimine and peiminine in rats, the absorption of peimine and peiminine in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct ligation can significantly affect the absorption of peimine and peiminine, the Ka, and Papp values in the condition of pH 6.8 and pH 7.4 had significant difference (P<0.01), as drug concentration irlcreased, the absorption parameters of peimine and peiminine decreased, Ka and Papp between low concentrations and middle concentrations was significant difference (P<0.01). Verapamil can not affect Ka and Papp of peimine and peiminine which are in the extract (P> 0.05). Bitter almonds and licorice can significantly reduce the absorption of peimine and peiminine with the usual dose (P<0.01), extracted separately and together had no significant difference on Ka and Papp (P> 0.05). Experimental results show that the absorption features of peimine and peiminine are basically the same, both of them could be absorbed at all segments of the intestine in rats and had no special absorption window, and with significant differences between male and female individuals. The absorption of peimine and peiminine complies with the active transport and facilitated diffusion in the general intestinal segments. Bitter almond and licorice can reduce the intestinal absorption rate ofpeimine and peiminine.

  20. Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology.

    PubMed

    Attari, Zenab; Bhandari, Amita; Jagadish, P C; Lewis, Shaila

    2016-01-01

    The purpose of this study was to develop nanosuspension based on combinative technology to enhance the intestinal absorption of Olmesartan medoxomil (OLM), a potent antihypertensive agent with limited oral bioavailability. Two combinative approaches were employed and then characterized. In vitro intestinal absorption of OLM nanosuspension and plain OLM was studied using non-everted rat intestinal sac model. Optimal OLM nanosuspension was prepared by a combination of ball milling and probe sonication using stabilizer, Poloxamer 407. The formula exhibited particle size of 469.9 nm and zeta potential of -19.1 mV, which was subjected to ex vivo studies. The flux and apparent permeability coefficient in intestine from OLM nanosuspension was higher than the plain drug, thereby suggesting better drug delivery.

  1. Amino acid and peptide absorption after proximal small intestinal resection in the rat.

    PubMed Central

    Garrido, A B; Freeman, H J; Chung, Y C; Kim, Y S

    1979-01-01

    In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation. PMID:428822

  2. Intestinal adaptation in patients with short bowel syndrome. Measurement by calcium absorption

    SciTech Connect

    Gouttebel, M.C.; Saint Aubert, B.; Colette, C.; Astre, C.; Monnier, L.H.; Joyeux, H. )

    1989-05-01

    Functional adaptation of remaining intestine was evaluated in 30 patients with extensive small bowel resection. Calcium and xylose absorption tests were compared. Calcium absorption was measured by a double-radiotracer technique. Serum xylosemia was measured 2 hr after D-xylose ingestion. Patients were divided into two groups according to the time interval between surgery and evaluation: less (group I) or more (group II) than two years. A statistically significant correlation was found between xylosemia and remaining small bowel length (r = 0.71; P less than 0.001) and between calcium absorption and remaining small bowel length (r = 0.75; P less than 0.001) in group I. A significant correlation was also observed between calcium absorption and time after surgery (r = 0.65; P = 0.001) but not for xylose absorption. Calcium absorption value was significantly increased in group II patients compared with group I patients matched for remaining small bowel length (36.2 +/- 12.5% vs 14.5 +/- 9.1%; P less than 0.001) while no difference was observed between the two groups concerning xylose absorption. These data indicate that intestinal calcium absorption continues to increase for more than two years after a major bowel resection in man. The intestine does not seem to recover all its functions at the same time.

  3. Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption.

    PubMed

    Yoshimatsu, Hiroki; Yonezawa, Atsushi; Yao, Yoshiaki; Sugano, Kumiko; Nakagawa, Shunsaku; Omura, Tomohiro; Matsubara, Kazuo

    2014-01-01

    Riboflavin, also known as vitamin B2, is transported across the biological membrane into various organs by transport systems. Riboflavin transporter RFVT3 is expressed in the small intestine and has been suggested to localize in the apical membranes of the intestinal epithelial cells. In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [(3)H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na(+) depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [(3)H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor methylene blue and significantly decreased by transfection of RFVT3-small-interfering RNA. In the gastrointestinal tract, RFVT3 was expressed in the jejunum and ileum. Mouse jejunal and ileal permeabilities of [(3)H]riboflavin were measured by the in situ closed-loop method and were significantly reduced by methylene blue. These results strongly suggest that RFVT3 would functionally be involved in riboflavin absorption in the apical membranes of intestinal epithelial cells.

  4. Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation.

    PubMed

    Yeap, Yan Yan; Trevaskis, Natalie L; Quach, Tim; Tso, Patrick; Charman, William N; Porter, Christopher J H

    2013-05-06

    The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by coadministration with lipids in food or lipid-based oral formulations. Coadministration with lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phases remain poorly understood. Classically, drug absorption is believed to be a product of the drug concentration in free solution and the apparent permeability across the absorptive membrane. Solubilization in colloidal phases such as mixed micelles increases dissolution rate and total solubilized drug concentrations, but does not directly enhance (and may reduce) the free drug concentration. In the absence of changes to cellular permeability (which is often high for lipophilic, PWSD), significant changes to membrane flux are therefore unexpected. Realizing that increases in effective dissolution rate may be a significant driver of increases in drug absorption for PWSD, we explore here two alternate mechanisms by which membrane flux might also be enhanced: (1) collisional drug absorption where drug is directly transferred from lipid colloidal phases to the absorptive membrane, and (2) supersaturation-enhanced drug absorption where bile mediated dilution of lipid colloidal phases leads to a transient increase in supersaturation, thermodynamic activity and absorption. In the current study, collisional uptake mechanisms did not play a significant role in the absorption of a model PWSD, cinnarizine, from lipid colloidal phases. In contrast, bile-mediated dilution of model intestinal mixed micelles and vesicles led to drug supersaturation. For colloids that were principally micellar, supersaturation was maintained for a period sufficient to promote absorption. In contrast, for primarily vesicular systems, supersaturation resulted in rapid drug precipitation and no increase in drug absorption. This work suggests that ongoing

  5. Intestinal absorption of 5 chromium compounds in young black ducks (Anas rubripes)

    USGS Publications Warehouse

    Eastin, W.C.; Haseltine, S.D.; Murray, H.C.

    1980-01-01

    An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4 )2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3 )3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr in solution may be an important factor in determining absorption of Cr compounds from the small intestine.

  6. Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure.

    PubMed

    Seidner, Douglas L; Schwartz, Lauren K; Winkler, Marion F; Jeejeebhoy, Khursheed; Boullata, Joseph I; Tappenden, Kelly A

    2013-03-01

    Short bowel syndrome-associated intestinal failure (SBS-IF) as a consequence of extensive surgical resection of the gastrointestinal (GI) tract results in a chronic reduction in intestinal absorption. The ensuing malabsorption of a conventional diet with associated diarrhea and weight loss results in a dependency on parenteral nutrition and/or intravenous fluids (PN/IV). A natural compensatory process of intestinal adaptation occurs in the years after bowel resection as the body responds to a lack of sufficient functional nutrient-processing intestinal surface area. The adaptive process improves bowel function but is a highly variable process, yielding different levels of symptom control and PN/IV independence among patients. Intestinal rehabilitation is the strategy of maximizing the absorptive capacity of the remnant GI tract. The approaches for achieving this goal have been limited to dietary intervention, antidiarrheal and antisecretory medications, and surgical bowel reconstruction. A targeted pharmacotherapy has now been developed that improves intestinal absorption. Teduglutide is a human recombinant analogue of glucagon-like peptide 2 that promotes the expansion of the intestinal surface area and increases the intestinal absorptive capacity. Enhanced absorption has been shown in clinical trials by a reduction in PN/IV requirements in patients with SBS-IF. This article details the clinical considerations and best-practice recommendations for intestinal rehabilitation, including optimization of fluids, electrolytes, and nutrients; the integration of teduglutide therapy; and approaches to PN/IV weaning.

  7. Absorption and intestinal metabolism of SDZ-RAD and rapamycin in rats.

    PubMed

    Crowe, A; Bruelisauer, A; Duerr, L; Guntz, P; Lemaire, M

    1999-05-01

    The new immunosuppressive agent, SDZ-RAD, and its analog rapamycin were examined for intestinal absorption, metabolism, and bioavailability in Wistar rats. Intestinal first-pass metabolism studies from rat jejunum showed that at 0.5 mg of SDZ-RAD/kg rat, 50% of the parent compound was metabolized in the intestinal mucosa, and this decreased to around 30% when SDZ-RAD was increased to 5.0 mg/kg rat. Results for rapamycin at the low dose were similar to those for SDZ-RAD, but at the higher dose only 1 to 14% of the total rapamycin absorbed was metabolized by the intestine. After i.v. administration of 1 mg/kg SDZ-RAD or rapamycin, the area under the concentration curve (AUC) for rapamycin was twice that of SDZ-RAD, resulting in a systemic clearance of 6.2 ml/min and 3.0 ml/min for SDZ-RAD and rapamycin, respectively. However, the AUC for oral absorption was similar for the two compounds: 140 and 172 ng*h/ml for SDZ-RAD and rapamycin, respectively. Because blood clearance was faster for SDZ-RAD after i.v. administration, the absolute oral bioavailability for SDZ-RAD was 16% compared with 10% for rapamycin. Overall, the data suggest that intestinal first pass is a major site of metabolism for SDZ-RAD and rapamycin and that intestinal absorption of SDZ-RAD was much faster than that of rapamycin. This allowed it to counteract the combined actions of faster systemic clearance and increased intestinal metabolism, resulting in comparable absolute exposure when given orally. Also, the coadministration of cyclosporin A with SDZ-RAD was shown to dramatically increase blood AUCs for SDZ-RAD, probably through saturating intestinal metabolism mechanisms.

  8. The kinetics of intestinal calcium absorption in the rat: an analytical and model building study.

    PubMed

    de Labriolle-Vaylet, C; Bouvet, D; Brezillon, P; Milhaud, G; Staub, J F

    1986-04-01

    The experimental data obtained from in vivo single pass perfusion of duodenal, jejunal, and ileal intestinal segments of 33- and 50-day-old rats have been used to test a series of models for calcium absorption. Each model was checked for the statistical validity and goodness-of-fit with the experimental data. The model adopted for the duodenum and jejunum had two major components, one saturable and the other nonsaturable, and a minor secretory component. This model was not applicable to ileal calcium absorption. Here the secretory component appeared to be much more important, and the absorption parameters varied in such a manner as to suggest that this intestinal segment was capable of short term autoregulation of dietary calcium absorption.

  9. Intestinal folate binding protein (FBP) and folate absorption in the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1986-03-01

    The folate in milk is bound to high affinity FBPs but it is unknown whether this binding affects intestinal transport of milk folate in the suckling rat. The authors examined the FBP activity of segments of the GI tract in fed and fasting states. Under fed conditions, the FBP activity in the mucosa of the stomach and proximal small intestine were similar (0.28 and 0.32 pMole folic acid binding/mg protein, N.S.). Both demonstrated less activity than the mucosa of the distal small intestine (1.31 pMole/mg protein, P < .001). A 6 hr fast produced no change in the FBP activity in the stomach or proximal small intestine but resulted in a 42% decrease in the distal small intestine (p < .01). Intestinal transport of unbound and FB-bound H/sup 3/pteryolmonoglutamate (H/sup 3/PGA) was examined in suckling rats by the intestinal loop model. Unbound H/sup 3/PGA demonstrated greater lumenal disappearance in the proximal segment of the small intestine compared to the distal segment (79% vs. 56%, P < .001) whereas the bound H/sup 3/PGA demonstrated greater lumenal disappearance in the distal segment (36% vs. 21%, p < .005). That porton of FBP activity in the distal small intestine that disappears with fasting may represent FBP absorbed from the lumen of the intestine. The FBP-bound folate in milk appears to be absorbed in the suckling rat by a mechanism that favors the distal small intestine and is different from the mechanism responsible for absorption of the unbound folate.

  10. Mechanisms of guanylin action on water and ion absorption at different regions of seawater eel intestine.

    PubMed

    Ando, Masaaki; Wong, Marty K S; Takei, Yoshio

    2014-09-15

    Guanylin (GN) inhibited water absorption and short-circuit current (Isc) in seawater eel intestine. Similar inhibition was observed after bumetanide, and the effect of bumetanide was abolished by GN or vice versa, suggesting that both act on the same target, Na(+)-K(+)-2Cl(-) cotransporter (NKCC), which is a key player for the Na(+)-K(+)-Cl(-) transport system responsible for water absorption in marine teleost intestine. However, effect of GN was always greater than that of bumetanide: 10% greater in middle intestine (MI) and 40% in posterior intestine (PI) for Isc, and 25% greater in MI and 34% in PI for water absorption. After treatment with GN, Isc decreased to zero, but 20-30% water absorption still remained. The remainder may be due to the Cl(-)/HCO3 (-) exchanger and Na(+)-Cl(-) cotransporter (NCC), since inhibitors for these transporters almost nullified the remaining water absorption. Quantitative PCR analysis revealed the presence of major proteins involved in water absorption; the NKCC2β and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCCβ genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2β was MI > PI, and that of NCCβ was MI < PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na(+)-K(+)-Cl(-) transport system governed by NKCC2β, but also regulates unknown ion transporters different from GN-insensitive SLC26A6 and NCC. A candidate is cystic fibrosis transmembrane conductance regulator Cl(-) channel, as demonstrated in mammals, but its expression is low in eel intestine, and its role may be minor, as indicated by the small effect of its inhibitors.

  11. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    PubMed

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  12. Morphine-neural interactions on canine intestinal absorption and blood flow.

    PubMed Central

    Mailman, D.

    1984-01-01

    Intestinal Na and H2O fluxes and blood flow were determined in extrinsically denervated or innervated ileum of fed dogs during intra-arterial (0.2, 2, 20 micrograms min-1) or intraluminal (4, 40, 400 micrograms ml-1) morphine sulphate infusion. 3H2O and 22Na were used to determine unidirectional fluxes and 3H2O clearances were used to determine total segmental and absorptive site blood flow. Net Na and H2O absorption decreased with time in innervated gut segments but were unchanged in denervated segments. Intra-arterial morphine prevented the decrease in net Na and H2O absorption in innervated segments due to increases in unidirectional absorptive fluxes. Intra-arterial morphine did not affect absorption in denervated segments. Intraluminal morphine increased net Na and H2O absorption from both innervated and denervated ileal segments due to increases in the unidirectional absorptive fluxes. Absorptive site blood flow was linearly related to unidirectional absorptive Na fluxes in each group although not with the same slopes. The increment in absorptive site blood flow vs. absorptive Na flux was greatest with luminal morphine, intermediate with intra-arterial morphine and in denervated segments without morphine and least in innervated segments. It was concluded that intra-arterial morphine inhibits an antiabsorptive effect of extrinsic nerves and that intraluminal morphine promotes an absorptive effect which could be direct or mediated through intrinsic nerves. PMID:6704589

  13. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

    PubMed Central

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan

    2016-01-01

    ABSTRACT The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. IMPORTANCE The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd

  14. Coexisted components of Salvia miltiorrhiza enhance intestinal absorption of cryptotanshinone via inhibition of the intestinal P-gp.

    PubMed

    Dai, Haixue; Li, Xiaorong; Li, Xiaoli; Bai, Lu; Li, Yuhang; Xue, Ming

    2012-11-15

    Cryptotanshinone, derived from the roots of Salvia miltiorrhiza Bge and Salvia przewalskii Maxim, is the major active component and possesses significant antibacterial, antidermatophytic, antioxidant, anti-inflammatory and anticancer activities. The objective of this study was to investigate the intestinal absorptive characteristics of cryptotanshinone as well as the absorptive behavior influenced by co-administration of the diterpenoid tanshinones and danxingfang using an in vitro everted rat gut sac model. The results showed a good linear correlation between cryptotanshinone of absorption and the incubation time from 10 to 70min. The concentration dependence showed that a non-linear correlation existed between the cryptotanshinone absorption and the concentration at 100 μg/ml. Coexisting diterpenoid tanshinones and danxingfang could significantly enhance the absorption of cryptotanshinone. Coexisting diterpenoid tanshinones and danxingfang, which influenced cryptotanshinone's absorption, manifested as similar to that of the P-glycoprotein inhibitor. The underlying mechanism of the improvement of oral bioavailability was proposed that coexisting diterpenoid tanshinones and danxingfang could decrease the efflux transport of cryptotanshinone by P-glycoprotein.

  15. Involvement of Concentrative Nucleoside Transporter 1 in Intestinal Absorption of Trifluridine Using Human Small Intestinal Epithelial Cells.

    PubMed

    Takahashi, Koichi; Yoshisue, Kunihiro; Chiba, Masato; Nakanishi, Takeo; Tamai, Ikumi

    2015-09-01

    TAS-102, which is effective for refractory metastatic colorectal cancer, is a combination drug of anticancer trifluridine (FTD; which is derived from pyrimidine nucleoside) and FTD-metabolizing enzyme inhibitor tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5. To evaluate the intestinal absorption mechanism of FTD, the uptake and transcellular transport of FTD by human small intestinal epithelial cell (HIEC) monolayer as a model of human intestinal epithelial cells was investigated. The uptake and membrane permeability of FTD by HIEC monolayers were saturable, Na(+) -dependent, and inhibited by nucleosides. These transport characteristics are mostly comparable with those of concentrative nucleoside transporters (CNTs). Moreover, the uptake of FTD by CNT1-expressing Xenopus oocytes was the highest among human CNT transporters. The obtained Km and Vmax values of FTD by CNT1 were 69.0 μM and 516 pmol/oocyte/30 min, respectively. The transcellular transport of FTD by Caco-2 cells, where CNT1 is heterologously expressed, from apical to basolateral side was greater than that by Mock cells. In conclusion, these results demonstrated that FTD exhibits high oral absorption by the contribution of human CNT1.

  16. Absorption of theophylline from the small and large intestine of the neonatal piglet.

    PubMed

    Murray, R D; Breech, L; Ailabouni, A; Zingerelli, J; Nahata, M C

    1993-01-01

    In this study, the newborn piglet model was used to assess theophylline absorption from various areas of the GI tract. 13 piglets, ages 9-14 days, had their intestines surgically exposed. Four segments of equal length (jejunum, ileum, right colon and left colon) were simultaneously perfused with a saline solution containing [3H]-polyethylene glycol 4000 to measure water shifts and theophylline at a total dose of 5 mg/kg, a typical neonatal dose. Absorption of theophylline, appearance in serum, and the effects of the drug on water and electrolyte movement in the intestinal segments were monitored. Serum concentrations of theophylline after an intravenous and oral dose were also studied in 2 piglets. The data showed excellent absorption of the drug from all intestinal segments studied (jejunum 0.97 +/- 0.16, ileum 0.7 +/- 0.13, right colon 0.7 +/- 0.13, and left colon 0.88 +/- 0.19 micrograms/cm/min), despite a concomitant secretion of sodium chloride and water. No statistical differences in absorptive capacity were seen among segments. The results suggest that as little as 100 cm of residual intestine could, theoretically, absorb a 5 mg dose of theophylline if presented slowly. These findings have ramifications for neonates who may receive theophylline orally or rectally.

  17. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    PubMed

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications.

  18. Effect of abdominal surgery on the intestinal absorption of lipophilic drugs: possible role of the lymphatic transport.

    PubMed

    Gershkovich, Pavel; Itin, Constantin; Yacovan, Avihai; Amselem, Shimon; Hoffman, Amnon

    2009-06-01

    Although abdominal surgery is a routine procedure in clinical practice and in preclinical investigation, little is known regarding its effect on the intestinal absorption of drugs. The aim of this study was to investigate the effect of abdominal surgery on the intestinal absorption of highly lipophilic compounds with different absorption mechanisms following oral administration. The 2 compounds that were tested were biopharmaceutical classification system (BCS) class 2 model lipophilic cannabinoid derivatives, dexanabinol and PRS-211,220. Although dexanabinol is mostly absorbed via passive diffusion to the portal blood, PRS-211,220 is absorbed mostly via lymphatic transport. In this work, we compared the absorption of these compounds after abdominal surgery in rat with the absorption data obtained from naïve animals. The outcomes of this investigation showed that the abdominal surgery mostly affected the absorption process on the preenterocyte level, as indicated by the 2-fold increase in the extent of intestinal absorption of dexanabinol, which is a compound with a low degree of intestinal lymphatic transport. However, the lymphatic transport was not affected by the surgical procedure as evident by the absence of change in the extent of absorption of PRS-211,220, which is transported to the systemic circulation mainly by intestinal lymphatics. In conclusion, abdominal surgery can significantly affect the intestinal absorption of lipophilic drugs; however, intestinal lymphatic transport seems to be less affected by the abdominal surgery.

  19. [Intestinal absorption of aloe-emodin using single-passintestinal perfusion method in rat].

    PubMed

    Wang, Jinrong; Wang, Ping; Yang, Yongmao; Meng, Xianli; Zhang, Yan

    2011-09-01

    The intestinal absorption of aloe-emodin was investigated using the single pass intestinal perfusion (SPIP) technique in S/D rats. SPIP was performed in each isolated segment of the intestine (i.e., duodenum, jejunum, ileum and colon) and the different concentrations inhibitor group of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) with the concentrations of aloe-emodin (0.238 mg x L(-1)) at a flow rate of 0.28 mL x min(-1). The effective absorption rate constant (Ka) and apparent absorption coefficient (Papp) of aloe-emodin for each segment were determined before and after treated with different concentrations of inhibitors of P-gp and MRP2 respectively. Aloe-emodin exhibits a high intestinal permeability except the the ileum, indicative that the compounds are well absorbed. Decreases of Ka and Papp values in the duodenum, jejunum, colon and ileum, furthermore, the duodenum has significant increased compared with the ileum, there are have no significant difference in other isolated region of the intestine. Compared with the group which have no inhibitor of P-gp, the Ka and Papp were significantly increased in inhibitor of P-gp groups. Compared with the group of no inhibitor of MRP2, the Ka and Papp were significantly increased in inhibitor of MRP2 groups with the highest and the middle concentration. The results suggested that the inhibitors of P-gp and MRP2 all can promote the intestinal absorption of aloe-emodin.

  20. Intestinal Absorption of Hemoglobin Iron-Heme Cleavage by Mucosal Heme Oxygenase

    PubMed Central

    Raffin, Steven B.; Woo, Choong H.; Roost, Kenneth T.; Price, David C.; Schmid, Rudi

    1974-01-01

    Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-α, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic 55Fe from 55Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined. PMID:4436436

  1. Intestinal absorption of fucoidan extracted from the brown seaweed, Cladosiphon okamuranus.

    PubMed

    Nagamine, Takeaki; Nakazato, Kyoumi; Tomioka, Satoru; Iha, Masahiko; Nakajima, Katsuyuki

    2014-12-25

    The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro.

  2. [Effect of phosphate upon calcium intestinal absorption (author's transl)].

    PubMed

    Fournier, P; Dupuis, Y; Digaud, A; Fournier, A

    1976-11-01

    Adult rats receive 5 to 50 mM CaCl2 solutions in which glycerophosphate or sodium diacid phosphate may be added in variable quantity. These solutions are administered by gavage or in situ ligatured jejunal loop. The inhibition of calcium absorption dependent on simultaneously administered phosphate doses is well characterized: high for the lowest concentration, the inhibiting effect of phosphate doses decreases more and more reaching a limit from which phosphate supplementation has no effect. These observations discarding an intervention of phosphate by calcium insolubilization seem to demonstrate that the control supplied by phosphates on calcium absorption is of enzymatic character. Facts related to the respective effects of calcium and phosphates on the action of alkaline phosphatases lead to discuss a possible intervention of these enzymes upon calcium transfer.

  3. Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models.

    PubMed

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    2009-01-01

    Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 microM of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level.

  4. Enhanced intestinal absorption of daidzein by borneol/menthol eutectic mixture and microemulsion.

    PubMed

    Shen, Qi; Li, Xi; Li, Wenji; Zhao, Xinyi

    2011-12-01

    In the present study, the effect of a borneol/menthol eutectic mixture (25:75) and microemulsion on the absorption of daidzein in rat intestinal membrane was evaluated. The microemulsion formulation was composed of ethyl oleate (oil), Cremophor RH40 (surfactant), PEG400 (co-surfactant), and water. The borneol/menthol eutectic mixture and its microemulsion were found to enhance the intestinal absorption of daidzein in vitro. A diffusion chamber system with isolated rat intestinal membranes was used. In contrast, verapamil (0.3 mM), a typical P-glycoprotein inhibitor, showed no effect on the absorption of daidzein by this system. A pharmacokinetic study was conducted in rats. After oral administration of daidzein at a dose of 10 mg/kg in the form of either borneol/menthol eutectic mixtures or suspension, the relative bioavailability of borneol/menthol eutectic mixtures and microemulsion was enhanced by about 1.5- and 3.65-fold, respectively, compared with a daidzein suspension. In conclusion, a borneol/menthol eutectic mixture can enhance the absorption of daidzein, although the mechanism of absorption enhancement is still unclear.

  5. Intestinal perfusion indicates high reliance on paracellular nutrient absorption in an insectivorous bat Tadarida brasiliensis.

    PubMed

    Price, Edwin R; Brun, Antonio; Fasulo, Verónica; Karasov, William H; Caviedes-Vidal, Enrique

    2013-02-01

    Flying vertebrates have been hypothesized to have a high capacity for paracellular absorption of nutrients. This could be due to high permeability of the intestines to nutrient-sized molecules (i.e., in the size range of amino acids and glucose, MW 75-180 Da). We performed intestinal luminal perfusions of an insectivorous bat, Tadarida brasiliensis. Using radio-labeled molecules, we measured the uptake of two nutrients absorbed by paracellular and transporter-mediated mechanisms (L-proline, MW 115 Da, and D-glucose, MW 180 Da) and two carbohydrates that have no mediated transport (L-arabinose, MW 150 Da, and lactulose, MW 342 Da). Absorption of lactulose (0.61±0.06 nmol min(-1) cm(-1)) was significantly lower than that of the smaller arabinose (1.09±0.04 nmol min(-1) cm(-1)). Glucose absorption was significantly lower than that of proline at both nutrient concentrations (10mM and 75 mM). Using the absorption of arabinose to estimate the portion of proline absorption that is paracellular, we calculated that 25.1±3.0% to 66.2±7.8% of proline absorption is not transporter-mediated (varying proline from 1 mM to 75 mM). These results confirm our predictions that 1) paracellular absorption is molecule size selective, 2) absorption of proline would be greater than glucose absorption in an insectivore, and 3) paracellular absorption represents a large fraction of total nutrient absorption in bats.

  6. In vivo regulation of intestinal absorption of amino acids by leptin.

    PubMed

    Fanjul, Carmen; Barrenetxe, Jaione; De Pablo-Maiso, Lorena; Lostao, María Pilar

    2015-01-01

    Leptin is secreted by the gastric mucosa and is able to reach the intestinal lumen and bind to its receptors located in the apical membranes of enterocytes. We have previously demonstrated that apical leptin inhibits uptake of amino acids in rat intestine in vitro and in Caco-2 cells. The aim of the present work was to investigate the effect of leptin on absorption of amino acids using in vivo techniques, which generate situations closer to physiological conditions. In vivo intestinal absorption of amino acids in rats was measured by isolating a jejunal loop and using the single-pass perfusion system. Disappearance of glutamine (Gln), proline (Pro), and β-alanine (β-Ala) from the perfusate, in the absence or presence of leptin, was measured using a radioactivity method. Luminal leptin (25 nM) inhibited the absorption of 2 mM Pro, 5 mM β-Ala, and 5 mM Gln by approximately 45% after 5-15 min; the effect remained constant until the end of the experiment (80 min) and was rapidly and completely reversed when leptin was removed from the perfusion medium. Moreover, leptin was able to regulate the absorption of galactose and Gln in the same animal, indicating a direct action of the hormone on the specific transporters implicated in the uptake of each nutrient. The results of the present work indicate that luminal leptin decreases absorption of amino acids in vivo in a short-term manner and in a reversible way. These results, together with our previous findings, make it evident that leptin can be considered as a hormone which provides the intestine with a control mechanism to handle absorption of nutrients.

  7. Intestinal absorption and biological effects of orally administered amorphous silica particles

    PubMed Central

    2014-01-01

    Although amorphous silica nanoparticles are widely used in the production of food products (e.g., as anticaking agents), there is little information available about their absorption and biological effects after oral exposure. Here, we examined the in vitro intestinal absorption and in vivo biological effects in mice of orally administered amorphous silica particles with diameters of 70, 300, and 1,000 nm (nSP70, mSP300, and mSP1000, respectively) and of nSP70 that had been surface-modified with carboxyl or amine groups (nSP70-C and nSP70-N, respectively). Analysis of intestinal absorption by means of the everted gut sac method combined with an inductively coupled plasma optical emission spectrometer showed that the intestinal absorption of nSP70-C was significantly greater than that of nSP70. The absorption of nSP70-N tended to be greater than that of nSP70; however, the results were not statistically significant. Our results indicate that silica nanoparticles can be absorbed through the intestine and that particle diameter and surface properties are major determinants of the degree of absorption. We also examined the biological effects of the silica particles after 28-day oral exposure in mice. Hematological, histopathological, and biochemical analyses showed no significant differences between control mice and mice treated with the silica particles, suggesting that the silica nanoparticles evaluated in this study are safe for use in food production. PMID:25288919

  8. Studies on the Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Waldron-Edward, Deirdre; Paul, T. M.; Skoryna, Stanley C.

    1964-01-01

    A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to be available to the body. Studies were carried out by measuring bone uptake of Sr89 and Ca45 when various amounts of sodium alginate were fed with the diet. Long-term studies were made in which two different levels of radioactivity were used, to determine the pattern of Sr89 deposition with continuous intake of binding agent. It was found that administration of sodium alginate as a jelly overcomes the problem of constipation and effectively reduces Sr89 uptake, up to 83%. This fact represents a significant finding with respect to the use of the compound in human subjects. Addition of sodium alginate to drinking water is effective with low levels of Sr89 intake. This naturally occurring water-soluble macromolecular substance possesses several advantages in use for the suppression of absorption of radioactive strontium when compared with synthetic ion exchange resins: there is no disturbance of electrolyte balance; efficiency is not reduced by treatment over a prolonged period of time; and finally, the product is palatable. PMID:14222668

  9. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    PubMed

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  10. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

    PubMed

    Luo, Menghua; Fernández-Estívariz, Concepción; Manatunga, Amita K; Bazargan, Niloofar; Gu, Li H; Jones, Dean P; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Leader, Lorraine M; Galloway, John R; Ziegler, Thomas R

    2007-01-01

    Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared

  11. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    PubMed

    Kannisto, Kristina; Gåfvels, Mats; Jiang, Zhao-Yan; Slätis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gösta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol.

  12. Whey protein hydrolysates enhance water absorption in the perfused small intestine of anesthetized rats.

    PubMed

    Ito, Kentaro; Yamaguchi, Makoto; Noma, Teruyuki; Yamaji, Taketo; Itoh, Hiroyuki; Oda, Munehiro

    2016-08-01

    We evaluated the effect of whey protein hydrolysates (WPH) on the water absorption rate in the small intestine using a rat small intestine perfusion model. The rate was significantly higher with 5 g/L WPH than with 5 g/L soy protein hydrolysates or physiological saline (p < 0.05). WPH dose-dependently increased the water absorption rate in the range of 1.25-10.0 g/L. WPH showed a significantly higher rate than an amino acid mixture whose composition was equal to that of WPH (p < 0.05). The addition of 4-aminomethylbenzoic acid, an inhibitor of PepT1, significantly suppressed WPH's enhancement of water absorption (p < 0.05). The rate of water absorption was significantly correlated with that of peptides/amino acids absorption in WPH (r = 0.82, p < 0.01). These data suggest that WPH have a high water absorption-promoting effect, to which PepT1 contributes.

  13. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells--A Review.

    PubMed

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-09-08

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells.

  14. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review

    PubMed Central

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  15. Intestinal absorption of dietary fat from a liquid diet perfused in rats at a submaximum level.

    PubMed

    Simko, V; Kelley, R E

    1988-02-01

    The small intestine of rats was perfused in vivo for 2 h with a nutritionally complete liquid diet (68% calories from fat as corn oil). As the perfusion increased from 106 mg/2 h, the intestinal disappearance of the 14C-triolein marker remained proportional to the load up to 2,359 mg fat/2 h. Despite a decrease in absorption from 70 to 17%, this represents a very large fat intake. Fat absorption improved when medium-chain triglycerides or octanoic acid replaced corn oil (both p less than 0.01). Linoleic acid was absorbed from the diet less than corn oil (p less than 0.01). Dry ox bile reduced fat absorption (p less than 0.05); lipase and an antacid had no effect. Corn oil perfused alone was absorbed better than from the diet (p less than 0.01). Data with 14C-triolein was confirmed by dry-weight disappearance of the diet and by net intestinal water balance. Usual feeding underutilizes a large reserve for fat absorption. This reserve should be considered in therapeutic nutrition.

  16. Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

    PubMed

    Liang, Kai; Zhai, Shuiting; Zhang, Zhidong; Wang, Guoquan; Fu, Xiaoyang; Li, Tianxiao

    2016-07-01

    In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different.

  17. Studies on different iron source absorption by in situ ligated intestinal loops of broilers.

    PubMed

    Jia, Y F; Jiang, M M; Sun, J; Shi, R B; Liu, D S

    2015-02-01

    The objective of this study was to investigate the iron source absorption in the small intestine of broiler. In situ ligated intestinal loops of 70 birds were poured into one of seven solutions, including inorganic iron (FeSO4, Fe2(SO4)3), organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)), the mixtures (FeSO4 with glycine (Fe+Gly(II)), Fe2(SO4)3 with glycine (Fe+Gly(III)), and no Fe source (control). The total volume of 3-mL solution (containing 1 mg of elemental Fe) was injected into intestinal loops, and then 120-min incubation was performed. Compared with inorganic iron groups, in which higher FeSO4 absorption than Fe2(SO4)3 was observed, supplementation with organic Fe glycine chelate significantly increased the Fe concentration in the duodenum and jejunum (P < 0.05), however, decreased DMT1 and DcytB messenger RNA (mRNA) levels (P < 0.05). Organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)) increased serum iron concentration (SI), compared with inorganic 3 valence iron groups (Fe2(SO4)3 and Fe+Gly(III)) (P < 0.05); moreover, lower TIBC value was observed for the chelate (P < 0.05); however, mixture of inorganic iron and glycine did not have a positive role at DMT1 and DcytB mRNA levels, SI and Fe concentrations in the small intestine. Those results indicated that the absorption of organic Fe glycine chelate was more effective than that of inorganic Fe, and the orders of iron absorption in the small intestine were: Fe-Gly(II), Fe-Gly(III) > FeSO4, Fe+Gly(II) > Fe2(SO4)3, Fe+Gly(III). Additionally, the simple mixture of inorganic iron and glycine could not increase Fe absorption, and the duodenum was the main site of Fe absorption in the intestines of broilers and the ileum absorbed iron rarely.

  18. Clay ingestion enhances intestinal triacylglycerol hydrolysis and non-esterified fatty acid absorption.

    PubMed

    Habold, Caroline; Reichardt, François; Le Maho, Yvon; Angel, Fabielle; Liewig, Nicole; Lignot, Jean-Hervé; Oudart, Hugues

    2009-07-01

    Consumption by animals and humans of earthy materials such as clay is often related to gut pathologies. Our aim was to determine the impact of kaolinite ingestion on glucose and NEFA transport through the intestinal mucosa. The expression of hexose transporters (Na/glucose co-transporter 1 (SGLT1), GLUT2, GLUT5) and of proteins involved in NEFA absorption (fatty acid transporter/cluster of differentiation 36 (FAT/CD36), fatty acid transport protein 4 (FATP4) and liver fatty acid binding protein (L-FABP)) was measured (1) in rats whose jejunum was perfused with a solution of kaolinite, and (2) in rats who ate spontaneously kaolinite pellets during 7 and 28 d. Also, we determined TAG and glucose absorption in the kaolinite-perfused group, and pancreatic lipase activity, gastric emptying and intestinal transit in rats orally administered with kaolinite. Glucose absorption was not affected by kaolinite perfusion or ingestion. However, kaolinite induced a significant increase in intestinal TAG hydrolysis and NEFA absorption. The cytoplasmic expression of L-FABP and FATP4 also increased due to kaolinite ingestion. NEFA may enter the enterocytes via endocytosis mainly since expression of NEFA transporters in the brush-border membrane was not affected by kaolinite. After uptake, rapid binding of NEFA by L-FABP and FATP4 could act as an intracellular NEFA buffer to prevent NEFA efflux. Increased TAG hydrolysis and NEFA absorption may be due to the adsorption properties of clay and also because kaolinite ingestion caused a slowing down of gastric emptying and intestinal transit.

  19. Intestinal fluid absorption in anadromous salmonids: importance of tight junctions and aquaporins

    PubMed Central

    Sundell, Kristina S.; Sundh, Henrik

    2012-01-01

    The anadromous salmonid life cycle includes both fresh water (FW) and seawater (SW) stages. The parr-smolt transformation (smoltification) pre-adapt the fish to SW while still in FW. The osmoregulatory organs change their mode of action from a role of preventing water inflow in FW, to absorb ions to replace water lost by osmosis in SW. During smoltification, the drinking rate increases, in the intestine the ion and fluid transport increases and is further elevated after SW entry. In SW, the intestine absorbs ions to create an inwardly directed water flow which is accomplished by increased Na+, K+-ATPase (NKA) activity in the basolateral membrane, driving ion absorption via ion channels and/or co-transporters. This review will aim at discussing the expression patterns of the ion transporting proteins involved in intestinal fluid absorption in the FW stage, during smoltification and after SW entry. Of equal importance for intestinal fluid absorption as the active absorption of ions is the permeability of the epithelium to ions and water. During the smoltification the increase in NKA activity and water uptake in SW is accompanied by decreased paracellular permeability suggesting a redirection of the fluid movement from a paracellular route in FW, to a transcellular route in SW. Increased transcellular fluid absorption could be achieved by incorporation of aquaporins (AQPs) into the enterocyte membranes and/or by a change in fatty acid profile of the enterocyte lipid bilayer. An increased incorporation of unsaturated fatty acids into the membrane phospholipids will increase water permeability by enhancing the fluidity of the membrane. A second aim of the present review is therefore to discuss the presence and regulation of expression of AQPs in the enterocyte membrane as well as to discuss the profile of fatty acids present in the membrane phospholipids during different stages of the salmonid lifecycle. PMID:23060812

  20. Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model.

    PubMed

    Jiang, Cui-Ping; He, Xin; Yang, Xiao-Lin; Zhang, Su-Li; Li, Hui; Song, Zi-Jing; Zhang, Chun-Feng; Yang, Zhong-Lin; Li, Ping

    2014-01-01

    To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 × 10(-4) cm/s and the absorption rate constant (Ka) was 0.62 × 10(-2) s(-1). Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms.

  1. The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.

    PubMed

    Chan, Kelvin; Liu, Zhong Qiu; Jiang, Zhi Hong; Zhou, Hua; Wong, Yuen Fan; Xu, Hong-Xi; Liu, Liang

    2006-02-20

    Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

  2. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  3. Very low density lipoproteins in intestinal lymph: role in triglyceride and cholesterol transport during fat absorption

    PubMed Central

    Ockner, Robert K.; Hughes, Faith B.; Isselbacher, Kurt J.

    1969-01-01

    The role of nonchylomicron very low density lipoproteins (VLDL, Sf 20-400) in the transport of triglyceride and cholesterol was studied during lipid absorption. Various long chain fatty acids were infused intraduodenally in the form of mixed fatty acid—mono-olein-taurocholate micelles; control animals received saline or taurocholate. As compared with controls, all fatty acids (palmitic, oleic, linoleic) resulted in significant increases in chylomicron (Sf > 400) triglyceride. In addition, palmitic acid resulted in a twofold increase in VLDL triglyceride, whereas with the absorption of oleic or linoleic acid VLDL triglyceride did not change significantly. Differences in triglyceride fatty acid composition between chylomicrons and VLDL were observed during lipid absorption. Although the absolute amount of endogenous cholesterol in intestinal lymph was not significantly affected by lipid absorption under these conditions, its lipoprotein distribution differed substantially among the lipid-infused groups. During palmitate absorption, VLDL cholesterol was similar to that in the taurocholate-infused controls, and was equal to chylomicron cholesterol. In contrast, during oleate and linoleate absorption the VLDL cholesterol fell markedly, and was less than half of the chylomicron cholesterol in these groups. The half-time of plasma survival of VLDL cholesterol-14C was found to be twice that of chylomicron cholesterol-14C. These studies demonstrate that dietary long chain fatty acids differ significantly in their effects upon the transport of triglyceride and cholesterol by lipoproteins of rat intestinal lymph. These findings, together with the observed differences in rates of removal of chylomicrons and VLDL from plasma, suggest that variations in lipoprotein production at the intestinal level may be reflected in differences in the subsequent metabolism of absorbed dietary and endogenous lipids. PMID:5355348

  4. Calorie Restriction Increases P-Glycoprotein and Decreases Intestinal Absorption of Digoxin in Mice.

    PubMed

    Renaud, Helen J; Klaassen, Curtis D; Csanaky, Iván L

    2016-03-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [(3)H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [(3)H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum-fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance.

  5. In vitro study of transporters involved in intestinal absorption of inorganic arsenic.

    PubMed

    Calatayud, Marta; Barrios, Julio A; Vélez, Dinoraz; Devesa, Vicenta

    2012-02-20

    Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs.

  6. Iron regulatory proteins control a mucosal block to intestinal iron absorption.

    PubMed

    Galy, Bruno; Ferring-Appel, Dunja; Becker, Christiane; Gretz, Norbert; Gröne, Hermann-Josef; Schümann, Klaus; Hentze, Matthias W

    2013-03-28

    Mammalian iron metabolism is regulated systemically by the hormone hepcidin and cellularly by iron regulatory proteins (IRPs) that orchestrate a posttranscriptional regulatory network. Through ligand-inducible genetic ablation of both IRPs in the gut epithelium of adult mice, we demonstrate that IRP deficiency impairs iron absorption and promotes mucosal iron retention via a ferritin-mediated "mucosal block." We show that IRP deficiency does not interfere with intestinal sensing of body iron loading and erythropoietic iron need, but rather alters the basal expression of the iron-absorption machinery. IRPs thus secure sufficient iron transport across absorptive enterocytes by restricting the ferritin "mucosal block" and define a basal set point for iron absorption upon which IRP-independent systemic regulatory inputs are overlaid.

  7. Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

    USGS Publications Warehouse

    Serafin, J.A.

    1984-01-01

    Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique. bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards. Mallards absorbed less dieldrin and mercury than black-crowned night-herons. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

  8. Intestinal glucose absorption in calves as affected by different carbohydrate sources.

    PubMed

    Klinger, S; Noci, B; Müller, K; Breves, G

    2013-04-01

    From numerous recent studies, it has been demonstrated that the development of the forestomach system in ruminants and thus microbial carbohydrate fermentation do not exclude the potential of the small intestines for enzymatic carbohydrate digestion and subsequent monosaccharide absorption. However, the role of regulatory nutritional factors is still under discussion. Therefore, we investigated the kinetic parameters of intestinal Na(+) -dependent glucose absorption and SGLT1 expression using isolated brush border membrane vesicles (BBMV) from the jejunum of 10-week-old calves kept on either hay, concentrate or corn silage-based diets in addition to milk replacer. While the maximal transport capacity was significantly higher for concentrate and corn silage-fed animals, SGLT1 protein expression was highest in BBMV isolated from hay-fed animals. This observation differs from the prevalent conception that induction of Na(+) -dependent glucose uptake via SGLT1 is based on an increased number of transporters at the brush border membrane.

  9. Influence of dietary fat on the intestinal absorption of lipophilic compounds in goldfish (Carassius auratus).

    PubMed

    Sharifi, M; Connell, W D; Gabric, A

    1997-12-01

    Dietary uptake of a mixture of pp'DDT and four chlorobenzenes from diets with different lipid contents was measured in goldfish (Carassius auratus) in order to investigate the mechanism of intestinal absorption of organic compounds. The results of the experiments suggest that intestinal absorption is basically controlled by chemical diffusion rather than lipid coassimilation. The extent of dietary uptake as indicated by biomagnification factor was strongly correlated with the chemical log Kow, indicating that uptake of the chemicals from the gastrointestinal fluid is similar to the uptake from other aqueous environments and lipid content of the food in the range used in these experiments (2.9-10.9%) could not influence the uptake of lipophilic chemicals.

  10. Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans

    SciTech Connect

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-03-01

    The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

  11. Influence of phosvitin and calcium gluconate concentration on permeation and intestinal absorption of calcium ions.

    PubMed

    Dolińska, Barbara; Łopata, Katarzyna; Mikulska, Agnieszka; Leszczyńska, Lucyna; Ryszka, Florian

    2012-06-01

    The effect of egg yolk phosvitin on the permeation and absorption of calcium was investigated in vitro in relation to calcium gluconate concentration. Obtained results indicate that phosvitin significantly reduces the intestinal calcium absorption from 1 and 10 mM of calcium gluconate solution. It is associated with the formation of the complex of Ca (II) ions with phosvitin. The process of calcium permeation increases under phosvitin influence when calcium gluconate concentrations rise up to 10 mM. At a higher concentration of calcium gluconate (20 mM), no effect of phosvitin was seen on permeation of calcium ions.

  12. Effects of quercetin and menadione on intestinal calcium absorption and the underlying mechanisms.

    PubMed

    Marchionatti, Ana M; Pacciaroni, Adriana; Tolosa de Talamoni, Nori G

    2013-01-01

    Quercetin (QT) could be considered as a potential therapeutic agent for different diseases due to its antioxidant, anti-inflammatory, antiviral and anticancer properties. This study was designed to investigate the ability of QT to protect the chick intestine against menadione (MEN) induced injury in vivo and in vitro. Four-week old chicks (Gallus gallus) were treated i.p. with 2.5μmol of MEN/kg b.w. or with i.l. 50μM QT or both. QT protected the intestinal Ca(2+) absorption against the inhibition caused by MEN, but QT alone did not modify. Glutathione (GSH) depletion provoked by MEN in chick enterocytes was abolished by QT treatment, whereas QT alone did not modify the intestinal GSH content. The enhancement of GSH peroxidase activity produced by MEN was blocked by QT treatment. In contrast, superoxide dismutase activity remained high after simultaneous treatment of enterocytes with MEN and QT. The flavonol also avoided changes in the mitochondrial membrane permeability (swelling) produced by MEN. The FasL/Fas/caspase-3 pathway was activated by MEN, effect that was abrogated by QT. In conclusion, QT may be useful in preventing inhibition of chick intestinal Ca(2+) absorption caused by MEN or other substances that deplete GSH, by blocking the oxidative stress and the FasL/Fas/caspase-3 pathway activation.

  13. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin.

    PubMed

    Huo, Xiaokui; Liu, Qi; Wang, Changyuan; Meng, Qiang; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Liu, Kexin

    2013-11-20

    Bestatin is an immunomodulator with antitumor activity. This study was performed to investigate the effect of P-gp on the intestinal absorption and antiproliferative activity of bestatin. Our results showed that P-gp inhibitors significantly increased rat intestinal absorption of bestatin in vivo and in vitro. The net efflux ratio of bestatin was 2.2 across mock-/MDR1-MDCK cell monolayers and was decreased by P-gp inhibitors, indicating bestatin was a substrate of P-gp. Furthermore, the IC50 values of bestatin on U937 and K562 cells were decreased dramatically and the intracellular concentrations of bestatin were increased by incubation of cells with verapamil or Cyclosporin A. K562/ADR cells exhibited a higher IC50 value and a lower intracellular level of bestatin. The bestatin level in K562/ADR cells was partially restored by incubation with doxorubicin. However, P-gp and APN mRNA levels were not changed by bestatin. These results suggested that the intestinal absorption and accumulation in cancer cells for bestatin were limited by P-gp-mediated efflux. Additional attention should be paid to the alternative exposure of bestatin when bestatin was coadministered with drugs as P-gp substrates in clinic.

  14. Effect of chito-oligosaccharide on the intestinal absorptions of phenylethanoid glycosides in Fructus Forsythiae extract.

    PubMed

    Zhou, Wei; Tan, Xiaobin; Shan, Jinjun; Liu, Ting; Cai, Baochang; Di, Liuqing

    2014-10-15

    Phenylethanoid glycosides, the main active ingredients in Fructus Forsythiae extract possesses strong antibacterial, antioxidant and antiviral effects, and their contents were higher largely than that of other ingredients such as lignans and flavones, but their absolute bioavailability orally was significantly low, which influenced clinical efficacies of its oral preparations seriously. In the present study, the absorption mechanism of phenylethanoid glycosides was studied using in vitro Caco-2 cell model. And the effect of chito-oligosaccharide (COS) on the intestinal absorption of phenylethanoid glycosides in Fructus Forsythiae extract was investigated using in vitro, in situ and in vivo models. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenylethanoid glycosides in Fructus Forsythiae extract so with that in monomers was mainly restricted by the tight junctions, and influenced by efflux transporters (P-gp and MRP2). Meanwhile, the absorption of phenylethanoid glycosides in Fructus Forsythiae extract could be improved by COS. Besides, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenylethanoid glycosides compared to the control group (p<0.05), and was all safe for the Caco-2 cells. The observations from single-pass intestinal perfusion in situ model showed that the intestinal absorption of phenylethanoid glycosides can be enhanced by COS. Meanwhile, the absorption enhancing effect of phenylethanoid glycosides might be saturable in different intestine sites. In pharmacokinetics study, COS at dosage of 25mg/kg improved the bioavailability of phenylethanoid glycosides in Fructus Forsythiae extract to the greatest extent, and was safe for gastrointestine from morphological observation. In addition

  15. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.

    PubMed

    Yan, Chengyun; Gu, Jiwei; Lv, Yuguang; Shi, Weiguo; Jing, Hongying

    2017-03-16

    In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1-1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1-0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.

  16. Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

    PubMed

    Cai, Zheng; Huang, Juan; Luo, Hui; Lei, Xiaolu; Yang, Zhaoxiang; Mai, Yang; Liu, Zhongqiu

    2013-07-01

    Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.

  17. In vivo application of chitosan to facilitate intestinal acyclovir absorption in rats.

    PubMed

    Masuda, Ayumi; Goto, Yuko; Kurosaki, Yuji; Aiba, Tetsuya

    2012-07-01

    The effect of chitosan on the intestinal absorption of acyclovir (ACV) was evaluated in rats, and factors influencing its facilitative effect on the ACV absorption were examined. When ACV solution containing 1% chitosan with an average molecular weight of 150 kDa was administered into the upper jejunum, a significant increase in the plasma ACV concentration was observed, with the peak ACV concentration being eight times greater than that observed with the chitosan-free solution. The chitosan-free ACV solution, whose viscosity was adjusted to remain unchanged with polyethylene glycol, did not cause an increase in the plasma concentration, and neither did the chitosan-free solutions substitutionally containing low molecular cationic compounds, triethanolamine and kanamycin. When chitosan was digested with chitosanase to shorten its polycationic polysaccharide structure, chitosan subjected to 150-min digestion retained its facilitative effect on ACV absorption, but that subjected to 420-min digestion no longer caused facilitation, in which its average molecular weight was reduced to around 10 kDa. It is therefore indicated that intestinal ACV absorption can be facilitated with chitosan, and that it is necessary for chitosan to have a certain length of polycationic polysaccharide structure to exert such facilitation.

  18. Proliposome powders for enhanced intestinal absorption and bioavailability of raloxifene hydrochloride: effect of surface charge.

    PubMed

    Velpula, Ashok; Jukanti, Raju; Janga, Karthik Yadav; Sunkavalli, Sharath; Bandari, Suresh; Kandadi, Prabhakar; Veerareddy, Prabhakar Reddy

    2013-12-01

    The primary goal of the present study was to investigate the combined prospective of proliposomes and surface charge for the improved oral delivery of raloxifene hydrochloride (RXH). Keeping this objective, the present systematic study was focused to formulate proliposomes by varying the ratio of hydrogenated soyphosphatidylcholine and cholesterol. Furthermore, to assess the role of surface charge on improved absorption of RXH, anionic and cationic vesicles were prepared using dicetyl phosphate and stearylamine, respectively. The formulations were characterized for size, zeta potential and entrapment efficiency. The improved dissolution characteristics assessed from dissolution efficiency, mean dissolution rate were higher for proliposome formulations. The solid state characterization studies indicate the transformation of native crystalline form of the drug to amorphous and/or molecular state. The higher effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of proliposomes and cationic surface charge for augment in absorption across gastro intestinal barrier. To draw the conclusions, in vivo pharmacokinetic study carried out in rats indicate a threefold enhancement in the rate and extent of absorption of RXH from cationic proliposome formulation which unfurl the potential of proliposomes and role of cationic charge for improved oral delivery of RXH.

  19. A kinetic approach to the study of absorption of solutes by isolated perfused small intestine

    PubMed Central

    Fisher, R. B.; Gardner, M. L. G.

    1974-01-01

    1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine. 2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid. 3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions. 4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume. 5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8·3 mM. 6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min. 7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min. 8. The Km for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion. 9. These findings emphasize problems in interpreting results from other types of intestinal preparation. 10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions. ImagesPlate 1 PMID:4422346

  20. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    PubMed

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

  1. Characterization of the oral absorption of several aminopenicillins: determination of intrinsic membrane absorption parameters in the rat intestine in situ

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Amidon, G. L.

    1992-01-01

    The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane parameters were determined using a modified boundary layer model (fitted value +/- S.E.): Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 1.14 +/- 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.

  2. A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption

    PubMed Central

    Widjaja-Adhi, M. Airanthi K.; Lobo, Glenn P.; Golczak, Marcin; Von Lintig, Johannes

    2015-01-01

    Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency. Surprisingly, responses to dietary supplementation with these compounds are quite variable between individuals. Genome-wide studies have associated common genetic polymorphisms in the BCO1 gene with this variability. The BCO1 gene encodes an enzyme that is expressed in the intestine and converts provitamin A carotenoids to vitamin A-aldehyde. However, it is not clear how this enzyme can impact the bioavailability and metabolism of other carotenoids such as xanthophyll. We here provide evidence that BCO1 is a key component of a regulatory network that controls the absorption of carotenoids and fat-soluble vitamins. In this process, conversion of β-carotene to vitamin A by BCO1 induces via retinoid signaling the expression of the intestinal homeobox transcription factor ISX. Subsequently, ISX binds to conserved DNA-binding motifs upstream of the BCO1 and SCARB1 genes. SCARB1 encodes a membrane protein that facilitates absorption of fat-soluble vitamins and carotenoids. In keeping with its role as a transcriptional repressor, SCARB1 protein levels are significantly increased in the intestine of ISX-deficient mice. This increase results in augmented absorption and tissue accumulation of xanthophyll carotenoids and tocopherols. Our study shows that fat-soluble vitamin and carotenoid absorption is controlled by a BCO1-dependent negative feedback regulation. Thus, our findings provide a molecular framework for the controversial relationship between genetics and fat-soluble vitamin status in the human population. PMID:25701869

  3. Prediction of Human intestinal absorption of compounds using artificial intelligence techniques.

    PubMed

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-04-04

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. In current work, we are presenting a comprehensive study of prediction of absorption. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds with prediction accuracy of 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development.

  4. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    SciTech Connect

    Limsuwan, T.; Lovell, R.T.

    1981-12-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks.

  5. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells[S

    PubMed Central

    Awada, Manar; Soulage, Christophe O.; Meynier, Anne; Debard, Cyrille; Plaisancié, Pascale; Benoit, Bérengère; Picard, Grégory; Loizon, Emmanuelle; Chauvin, Marie-Agnès; Estienne, Monique; Peretti, Noël; Guichardant, Michel; Lagarde, Michel; Genot, Claude; Michalski, Marie-Caroline

    2012-01-01

    Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to −19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine. PMID:22865918

  6. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells.

    PubMed

    Awada, Manar; Soulage, Christophe O; Meynier, Anne; Debard, Cyrille; Plaisancié, Pascale; Benoit, Bérengère; Picard, Grégory; Loizon, Emmanuelle; Chauvin, Marie-Agnès; Estienne, Monique; Peretti, Noël; Guichardant, Michel; Lagarde, Michel; Genot, Claude; Michalski, Marie-Caroline

    2012-10-01

    Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine.

  7. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei

    PubMed Central

    Yan, Xiang Mei; Kim, Chung-Hyo; Lee, Chul Kyu; Shin, Jang Sik; Cho, Il Hwan

    2010-01-01

    To investigate the intestinal absorption of a fibrinolytic and proteolytic lumbrokinase extracted from Eisenia andrei, we used rat everted gut sacs and an in situ closed-loop recirculation method. We extracted lumbrokinase from Eisenia andrei, and then raised polyclonal antibody against lumbrokinase. Fibrinolytic activity and proteolytic activity in the serosal side of rat everted gut sacs incubated with lumbrokinase showed dose- and time-dependent patterns. Immunological results obtained by western blotting serosal side solution using rat everted gut sacs method showed that lumbrokinase proteins between 33.6 and 54.7 kDa are absorbed mostly by the intestinal epithelium. Furthermore, MALDI-TOF mass spectrometric analysis of plasma fractions obtained by in situ recirculation method confirmed that lumbrokinase F1 is absorbed into blood. These results support the notion that lumbrokinase can be absorbed from mucosal lumen into blood by oral administration. PMID:20473377

  8. Vesicular transport and apotransferrin in intestinal iron absorption, as shown in the Caco-2 cell model.

    PubMed

    Moriya, Mizue; Linder, Maria C

    2006-02-01

    The potential roles of vesicular transport and apotransferrin (entering from the blood) in intestinal Fe absorption were investigated using Caco-2 cell monolayers with tight junctions in bicameral chambers as a model. As shown previously, addition of 39 microM apotransferrin (apoTf) to the basolateral fluid during absorption studies markedly stimulated overall transport of 1 microM (59)Fe from the apical to the basal chamber and stimulated its basolateral release from prelabeled cells, implicating endo- and exocytosis. Rates of transport more than doubled. Uptake was also stimulated, but only 20%. Specific inhibitors of aspects of vesicular trafficking were applied to determine their potential effects on uptake, retention, and basolateral (overall) transport of (59)Fe. Nocodazole and 5'-(4-fluorosulfonylbenzoyl)-adenosine each reduced uptake and basolateral transport up to 50%. Brefeldin A inhibited about 10%. Tyrphostin A8 (AG10) reduced uptake 35% but markedly stimulated basolateral efflux, particularly that dependent on apoTf. Cooling of cells to 4 degrees C (which causes depolymerization of microtubules and lowers energy availability) profoundly inhibited uptake and basolateral transfer of Fe (7- to 12-fold). Apical efflux (which was substantial) was not temperature affected. Our results support the involvement of apoTf cycling in intestinal Fe absorption and indicate that as much as half of the iron uses apoTf and non-apoTf-dependent vesicular pathways to cross the basolateral membrane and brush border of enterocytes.

  9. Oral IGF-I enhances nutrient and electrolyte absorption in neonatal piglet intestine.

    PubMed

    Alexander, A N; Carey, H V

    1999-09-01

    The effect of orally administered insulin-like growth factor-I (IGF-I) on small intestinal structure and function was studied in 5-day-old colostrum-deprived piglets. Human recombinant IGF-I (3.5 mg. kg(-1). day(-1)) or control vehicle was given orogastrically for 4 days. Body weights, jejunal and ileal mucosa wet and dry weights, and serum IGF-I levels were similar in the two groups. Small intestinal villus height and crypt depth and jejunal enterocyte microvillar dimensions were also similar between groups. Oral IGF-I produced higher rates of jejunal ion transport because of increased basal Na+ absorption. Short-circuit current responses to mucosal addition of D-glucose and L-alanine and net transepithelial absorption of 3-O-methylglucose were increased by IGF-I. Carrier-mediated uptake of D-glucose per milligram in everted jejunal sleeves was greater in IGF-I-treated piglets because of a significantly greater maximal rate of uptake. We conclude that rates of net Na+ and Na+-dependent nutrient absorption are enhanced in piglets treated with oral IGF-I, and this effect is independent of changes in mucosal mass or surface area.

  10. Low zinc status and absorption exist in infants with jejunostomies or ileostomies which persists after intestinal repair

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer s...

  11. Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes.

    PubMed

    Young, Richard L; Chia, Bridgette; Isaacs, Nicole J; Ma, Jing; Khoo, Joan; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K

    2013-10-01

    We previously established that the intestinal sweet taste receptors (STRs), T1R2 and T1R3, were expressed in distinct epithelial cells in the human proximal intestine and that their transcript levels varied with glycemic status in patients with type 2 diabetes. Here we determined whether STR expression was 1) acutely regulated by changes in luminal and systemic glucose levels, 2) disordered in type 2 diabetes, and 3) linked to glucose absorption. Fourteen healthy subjects and 13 patients with type 2 diabetes were studied twice, at euglycemia (5.2 ± 0.2 mmol/L) or hyperglycemia (12.3 ± 0.2 mmol/L). Endoscopic biopsy specimens were collected from the duodenum at baseline and after a 30-min intraduodenal glucose infusion of 30 g/150 mL water plus 3 g 3-O-methylglucose (3-OMG). STR transcripts were quantified by RT-PCR, and plasma was assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and in type 2 diabetic patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 × 10(4) and +5.8 × 10(4) copies, respectively) but decreased in healthy subjects during hyperglycemia (-1.4 × 10(4) copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 × 10(5) copies). Plasma 3-OMG concentrations were significantly higher in type 2 diabetic patients than in healthy control subjects during acute hyperglycemia. Intestinal T1R2 expression is reciprocally regulated by luminal glucose in health according to glycemic status but is disordered in type 2 diabetes during acute hyperglycemia. This defect may enhance glucose absorption in type 2 diabetic patients and exacerbate postprandial hyperglycemia.

  12. The use of low molecular weight protamine chemical chimera to enhance monomeric insulin intestinal absorption.

    PubMed

    He, Huining; Sheng, Jianyong; David, Allan E; Kwon, Young Min; Zhang, Jian; Huang, Yongzhuo; Wang, Jianxin; Yang, Victor C

    2013-10-01

    Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a non-toxic yet potent cell-penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogenous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five-folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery.

  13. Disordered Control of Intestinal Sweet Taste Receptor Expression and Glucose Absorption in Type 2 Diabetes

    PubMed Central

    Young, Richard L.; Chia, Bridgette; Isaacs, Nicole J.; Ma, Jing; Khoo, Joan; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K.

    2013-01-01

    We previously established that the intestinal sweet taste receptors (STRs), T1R2 and T1R3, were expressed in distinct epithelial cells in the human proximal intestine and that their transcript levels varied with glycemic status in patients with type 2 diabetes. Here we determined whether STR expression was 1) acutely regulated by changes in luminal and systemic glucose levels, 2) disordered in type 2 diabetes, and 3) linked to glucose absorption. Fourteen healthy subjects and 13 patients with type 2 diabetes were studied twice, at euglycemia (5.2 ± 0.2 mmol/L) or hyperglycemia (12.3 ± 0.2 mmol/L). Endoscopic biopsy specimens were collected from the duodenum at baseline and after a 30-min intraduodenal glucose infusion of 30 g/150 mL water plus 3 g 3-O-methylglucose (3-OMG). STR transcripts were quantified by RT-PCR, and plasma was assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and in type 2 diabetic patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 × 104 and +5.8 × 104 copies, respectively) but decreased in healthy subjects during hyperglycemia (−1.4 × 104 copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 × 105 copies). Plasma 3-OMG concentrations were significantly higher in type 2 diabetic patients than in healthy control subjects during acute hyperglycemia. Intestinal T1R2 expression is reciprocally regulated by luminal glucose in health according to glycemic status but is disordered in type 2 diabetes during acute hyperglycemia. This defect may enhance glucose absorption in type 2 diabetic patients and exacerbate postprandial hyperglycemia. PMID:23761104

  14. The Use of Low Molecular Weight Protamine Chemical Chimera to Enhance Monomeric Insulin Intestinal Absorption

    PubMed Central

    He, Huining; Sheng, Jianyong; David, Allan E.; Kwon, Young Min; Zhang, Jian; Huang, Yongzhuo; Wang, Jianxin; Yang, Victor C.

    2013-01-01

    Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a nontoxic yet potent cell penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogeneous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery. PMID:23863452

  15. A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine

    SciTech Connect

    Bergstedt, S.E.; Hayashi, H.; Kritchevsky, D.; Tso, P. )

    1990-09-01

    Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri(9,10 (n)-3H)oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl (1,3-14C)tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.

  16. Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.

    PubMed

    Lindahl, Anders; Sjöberg, Asa; Bredberg, Ulf; Toreson, Helena; Ungell, Anna-Lena; Lennernäs, Hans

    2004-01-01

    The first purpose of this study was to investigate the in vivo absorption, biliary secretion, and first-pass effect of fluvastatin following regional intestinal dosing in the rat. We also examined the membrane transport mechanisms and made in silico predictions of the relative importance of various intestinal regions to the human absorption of fluvastatin. Fluvastatin was administered intravenously (2, 10, and 20 micromol/kg) and into the duodenum (1.46, 2.92, 7.32, and 14.6 micromol/kg), jejunum (14.6 micromol/kg), ileum (1.46 and 14.6 mciromol/kg), and colon (1.46 and 14.6 micromol/kg) as a solution to conscious rats. In a separate group of rats, bile was collected after an i.v. dose of fluvastatin (2 micromol/kg). In the Caco-2 model the bidirectional transport of fluvastatin (16 microM) was investigated with and without various efflux inhibitors (verapamil, vinblastine, probenecid, and indomethacin, 160 microM). The human in vivo absorption of fluvastatin from an oral immediate release tablet and that from an oral extended release tablet (both 40 mg) were simulated in GastroPlus. Neither the dose nor the intestinal region influenced the bioavailability of fluvastatin significantly. The rate of absorption was, however, affected by both the dose and the site of administration; duodenum = jejunum > colon > ileum, and higher following the high dose. Increasing the i.v. dose from 2 to 20 micromol/kg decreased the clearance (26 +/- 3 to 12 +/- 1 mL/min/kg), the hepatic extraction (66 +/- 8 to 30 +/- 2%), and the volume of distribution (7.3 +/- 0.3 to 2.1 +/- 0.7 L/kg) for fluvastatin (p < 0.05). Neither bile cannulation nor bile sampling affected the pharmacokinetics. Fluvastatin was secreted into the bile, probably by active transport. The in vitro permeability for fluvastatin was high (>10 x 10(-6) cm/s). Indomethacin, but not the other inhibitors, affected the transport in both directions suggesting mrp2 to be involved. In silico, 93% of the dose was absorbed from

  17. Soybean impairs Na(+)-dependent glucose absorption and Cl- secretion in porcine small intestine.

    PubMed

    Boudry, Gaëlle; Lallès, Jean-Paul; Malbert, Charles Henri; Grøndahl, Marie Louise; Unmack, Martin Andreas; Skadhauge, Erik

    2003-01-01

    Recent evidence indicates that soybean, which is widely used in animal nutrition, could directly alter intestinal ion and nutrient transport. However, the mechanisms involved are still unknown. The aim of the study was to investigate the effect of three differently treated soybean products on the glucose and Cl- transport capacity in porcine small intestine by the Ussing chamber technique. Jejunal and ileal piglet epithelial tissues were pre-incubated with extracts of raw soybean flour (RSF), heated soybean flour (HSF), or ethanol heat-treated soybean protein concentrate (SPC). The Na(+)-dependent glucose co-absorption capacity was then measured as an increase in the short-circuit current (ISC) after luminal addition of D-glucose. The effect of the soybean products on cAMP-dependent Cl- secretion was measured as the increase in ISC after the addition of the phosphodiesterase inhibitor, theophylline, while nervous regulation of Cl- secretion was investigated by the addition of the enteric neurotransmitters; 5-hydroxytryptamine (5-HT), substance P and vasoactive intestinal polypeptide (VIP). Incubation with RSF and HSF induced a 30% decrease of the Na(+)-dependent glucose absorption capacity in the jejunum. The effect was similar for RSF in the ileum. Theophylline-induced secretion was decreased by 30% after incubation with RSF, HSF and SPC but only in the jejunum. 5-HT-, substance P- and VIP-induced secretion were not altered by incubation with soybean extracts except in the HSF-incubated where the substance P-induced secretion was significantly reduced. In conclusion, soybean contains ethanol-sensitive heat-insensitive compounds impairing Na(+)-dependent glucose absorption in the jejunum and ileum, and ethanol- and heat-insensitive compounds causing an acute impairment of cAMP-dependent jejunal secretion.

  18. Enhancing effects of chitosan and chitosan hydrochloride on intestinal absorption of berberine in rats.

    PubMed

    Chen, Wei; Fan, Dongjiao; Meng, Lingkuo; Miao, Yuqiang; Yang, Shenshen; Weng, Yan; He, Haibing; Tang, Xing

    2012-01-01

    Berberine chloride (BBR) is a plant alkaloid that has been used for centuries for treatment of inflammation, dysentery, and liver diseases. It is poorly absorbed from the gastrointestinal (GI) tract and its various clinical uses are limited because of its poor bioavailability. The object of the present study was to investigate the absorption enhancing effect of chitosan on BBR. Mixtures of BBR and chitosan were prepared and the absorption enhancement was investigated in rats. The results showed a dose-dependent absorption enhancement produced by chitosan. Formulations containing 0.5%, 1.5%, and 3.0% chitosan resulted in improvement of AUC(0-36 h) values by 1.9, 2.2, 2.5 times. The absorption enhancing ability of chitosan may be due to its ability to improve the BBR paracellular pathway in the intestinal tract. Chitosan hydrochloride, a salt of chitosan, was also investigated in this study. However, the addition of 2.0% and 3.3% chitosan hydrochloride to BBR solution did not produce any increase in either C(max) or AUC(0-36 h) of BBR. Subsequent solubility studies suggested that the reduced berberine chloride solubility in chitosan hydrochloride may limit the enhancement ability. This study showed that the optimum formulation producing the highest BBR absorption is the BBR solution containing 3.0% chitosan.

  19. Molecular and cellular studies on the absorption, function, and safety of food components in intestinal epithelial cells.

    PubMed

    Satsu, Hideo

    2017-03-01

    The intestinal tract comes into direct contact with the external environment despite being inside the body. Intestinal epithelial cells, which line the inner face of the intestinal tract, have various important functions, including absorption of food substances, immune functions such as cytokine secretion, and barrier function against xenobiotics by means of detoxification enzymes. It is likely that the functions of intestinal epithelial cells are regulated or modulated by these components because they are frequently exposed to food components at high concentrations. This review summarizes our research on the interaction between intestinal epithelial cells and food components at cellular and molecular levels. The influence of xenobiotic contamination in foods on the cellular function of intestinal epithelial cells is also described in this review.

  20. Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane.

    PubMed

    Khafagy, El-Sayed; Iwamae, Ruisha; Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-11-01

    We have reported that the cell-penetrating peptide (CPP) penetratin acts as a potential absorption enhancer in oral insulin delivery systems and that this action occurs through noncovalent intermolecular interactions. However, the region-dependent role of CPPs in intestinal insulin absorption has not been clarified. To identify the intestinal region where CPPs have the most effect in increasing insulin absorption, the region-dependent action of penetratin was investigated using in situ closed intestinal loops in rats. The order of the insulin area under the insulin concentration-time curve (AUC) increase effect by L-penetratin was ileum > jejunum > duodenum > colon. By contrast, the AUC order after coadministration of insulin with D-penetratin was colon > duodenum ≥ jejunum and ileum. We also compared the effects of the L- and D-forms of penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs used in this study, L- and D-PenetraMax produced the largest insulin AUCs. An absorption study using ilea pretreated with CPPs showed that PenetraMax had no irreversible effect on the intestinal epithelial membrane. The degradation of insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid. The half-life (t 1/2) of insulin increased from 14.5 to 23.7 and 184.7 min in the presence of L- and D-PenetraMax, respectively. These enzymatic degradation-resistant effects might contribute partly to the increased ileal absorption of insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the ability of the L- and D-forms of penetratin to increase intestinal insulin absorption was maximal in the ileum and the colon, respectively, and that D-PenetraMax is a powerful but transient enhancer of oral insulin absorption.

  1. Human chorionic gonadotropin promotes expression of protein absorption factors in the intestine of goldfish (Carassius auratus).

    PubMed

    Zhou, Y; Hao, G; Zhong, H; Wu, Q; Lu, S Q; Zhao, Q; Liu, Z

    2015-07-27

    Protein use is crucial for the ovulation and spawning of fish. Currently, limited information is available regarding the expression of protein absorption factors during the breeding seasons of teleosts and thus how various proteins involved in this process is not well-understood. The expression of CDX2, CREB, gluatamate dehydrogenase, LAT2, aminopeptidase N, PepT1, and SP1 were significantly elevated from the non-breeding season to the breeding season in female goldfish, and all proteins except PepT1 and SP1 were elevated in male goldfish. Injection of human chorionic gonadotropin upregulated the expression of all proteins except for aminopeptidase N in female goldfish and SP1 in male goldfish, suggesting a luteinizing hormone-inductive effect on protein absorption factors. Protein use in the intestine is increased during the breeding seasons as a result of increased luteinizing hormone.

  2. In vivo measurement of the absorption of strontium in the rumen and small intestine of sheep as an index of calcium absorption capacity.

    PubMed

    Hyde, Michelle L; Fraser, David R

    2014-09-14

    In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon simultaneous administration of an oral dose of stable Sr and radioactive calcium (r 0·98). The Ca absorption capacity of the rumen and small intestine was determined separately by either directing the solution into the rumen or by diverting it into the post-ruminal tract by vasopressin-induced closure of the ruminoreticular groove. The animals were treated with 1α-hydroxyvitamin D3 administered via subcutaneously implanted mini-osmotic pumps. The effect of elevated plasma 1,25-dihydroxycholecalciferol concentrations on the Ca absorption capacity of the alimentary tract was then determined. An increased rate of Sr absorption was observed in both the rumen and small intestine of sheep after treatment, although it is unclear whether the rumen possesses the same vitamin D-dependent Ca absorption pathway as the small intestine.

  3. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs.

    PubMed

    Iqbal, Jahangir; Boutjdir, Mohamed; Rudel, Lawrence L; Hussain, M Mahmood

    2014-11-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production.

  4. Effect of dietary phosphorus on intestinal phosphorus absorption in growing Holstein steers.

    PubMed

    Feng, X; Ronk, E; Hanigan, M D; Knowlton, K F; Schramm, H; McCann, M

    2015-05-01

    The effect of dietary P intake on intestinal P absorption was evaluated in growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%, DM basis) were fed to 8 steers (174±10kg of BW) fitted with permanent duodenal and ileal cannulas in a replicated 4×4 Latin square with 14-d periods. Ytterbium-labeled corn silage and cobalt-EDTA were used as particulate and liquid phase markers, respectively, to measure digesta flow. Duodenal and ileal samples and spot urine samples were collected every 9 h from d 11 to 14. Total fecal collection was conducted on d 11 to 14 with fecal bags. Blood samples were collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX in SAS with a model including treatment, square, period, and interaction of treatment and square. Preplanned contrasts were used to evaluate linear and quadratic treatment effects. Results were reported as least squares means. Dry matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80, 7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a net basis from the large intestine, but this was not affected by treatment and was a small proportion of total P absorption. Blood inorganic P increased linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P secretion was unchanged (mean=5.79g/d), suggesting that rumen function was prioritized during short-term P deficiency. These data showing an absence of change in absorption efficiency and salivary P secretion in the face of short-term P deficiency may be used to improve published

  5. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

    PubMed Central

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

    2015-01-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

  6. Clonidine and lidamidine (WHR-1142) stimulate sodium and chloride absorption in the rabbit intestine.

    PubMed

    Durbin, T; Rosenthal, L; McArthur, K; Anderson, D; Dharmsathaphorn, K

    1982-06-01

    The effects of clonidine and lidamidine on ion transport in the intestine of the rabbit were determined. In the ileum both clonidine (10(-6) M) and lidamidine (10(-3) M) (a) decreased the short circuit current (-1.9 +/- 0.3 and -2.0 +/- 0.4 muEq/h . cm2, respectively) and potential difference; (b) increased net sodium absorption (2.0 +/- 0.6 and 1.8 +/- 0.4 muEq/h . cm2) and chloride absorption (3.4 +/- 0.5 and 3.4 +/- 0.6 muEq/h . cm2); and (c) increased tissue conductance (8.7 +/- 1.7 and 10.0 +/- 1.6 mmho/cm2). The increase in net sodium and chloride absorption was primarily due to an increase in mucosal-to-serosal movement of the ions and a decrease in serosal-to-mucosal movement of chloride. The action of clonidine on the short circuit current was quantitatively similar to the action of epinephrine. Both were readily reversed by yohimbine, a specific alpha 2-adrenergic antagonist. Further, methoxamine, an alpha 1-adrenergic agonist has no effect on the short circuit current up to the concentration of 10(-5) M; and prazosin, an alpha 1-adrenergic antagonist, did not affect the change of the short circuit current induced by epinephrine. The results indicate the presence of alpha 2-adrenergic receptors on the intestine and suggest that alpha 2-adrenergic stimulation may account for the effect of epinephrine on ion transport. Lidamidine was studied because it is structurally related to clonidine and has many similar actions. Yohimbine transiently reversed the effect of lidamidine. alpha 1-Adrenergic or dopaminergic antagonists did not reverse the effect of lidamidine, suggesting that it may affect alpha 2-adrenergic receptors. The results indicate that both clonidine and lidamidine stimulate electrolyte absorption and may be clinically useful.

  7. Human Milk Oligosaccharides in Premature Infants: Absorption, Excretion and Influence on the Intestinal Microbiota

    PubMed Central

    Underwood, Mark A.; Gaerlan, Stephanie; De Leoz, M. Lorna A.; Dimapasoc, Lauren; Kalanetra, Karen M.; Lemay, Danielle G.; German, J. Bruce; Mills, David A.; Lebrilla, Carlito B.

    2015-01-01

    Background Human milk oligosaccharides (HMOs) shape the intestinal microbiota in term infants. In premature infants, alterations in the intestinal microbiota (dysbiosis) are associated with risk of necrotizing enterocolitis and sepsis and the influence of HMOs on the microbiota is unclear. Methods Milk, urine, and stool specimens from 14 mother-premature infant dyads were investigated by mass spectrometry for HMO composition. The stools were analyzed by next-generation sequencing (NGS) to complement a previous analysis. Results Percentages of fucosylated and sialylated HMOs were highly variable between individuals but similar in urine, feces and milk within dyads. Differences in urine and fecal HMO composition suggest variability in absorption. Secretor status of the mother correlated with the urine and fecal content of specific HMO structures. Trends toward higher levels of Proteobacteria and lower levels of Firmicutes, were noted in premature infants of non-secretor mothers. Specific HMO structures in the milk, urine and feces were associated with alterations in fecal Proteobacteria and Firmicutes. Conclusion HMOs may influence the intestinal microbiota in premature infants. Specific HMOs, for example those associated with secretor mothers, may have a protective effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis while other HMOs may increase dysbiosis in this population. PMID:26322410

  8. EFFECTS OF PUROMYCIN ON THE STRUCTURE OF RAT INTESTINAL EPITHELIAL CELLS DURING FAT ABSORPTION

    PubMed Central

    Friedman, Harold I.; Cardell, Robert R.

    1972-01-01

    This report provides information on the morphology of rat intestinal epithelial cells during fat absorption. In addition, the role of protein metabolism in this process has been evaluated by blocking its synthesis with puromycin and studying the fine structure of mucosal cells from rats at various times after fat intubation. The results indicate that SER-derived vesicles, containing fat droplets, migrate from the apical cytoplasm of the absorptive cell and fuse with saccules or vacuoles of the Golgi complex. Arguments are made that the Golgi complex is important in completing chylomicron formation and in providing appropriate enveloping membranes for the chylomicron. Such membranes may be necessary for Golgi vacuoles to fuse with the lateral cell membranes and release chylomicra. Puromycin treatment causes the absorptive cell to accumulate increased quantities of lipid that are devoid of membrane during fat absorption. In addition, puromycin-treated cells contain much less RER and Golgi membranes are strikingly decreased in number. In this paper we discuss the consequences of these abnormalities and suggest that continued protein synthesis by the RER is required in order to generate Golgi membranes. If such membranes are absent the cell's ability to discarge chylomicra is impaired and lipid accumulates. PMID:4331298

  9. Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3-Monochloropropanediol Esters.

    PubMed

    Kaze, Naoki; Watanabe, Yomi; Sato, Hirofumi; Murota, Kaeko; Kotaniguchi, Miyako; Yamamoto, Hiroshi; Inui, Hiroshi; Kitamura, Shinichi

    2016-08-01

    The regioisomers of the di- and mono-oleate of monochloropropanediol (MCPD) have been synthesized and subsequently hydrolyzed with pancreatic lipase and pancreatin to estimate the intestinal digestion and absorption of these compounds after their intake. The hydrolysates were analyzed by HPLC using a corona charged aerosol detection system, which allowed for the separation and detection of the different regioisomers of the MCPD esters. The hydrolysates were also analyzed by GC-MS to monitor the free MCPD. The results indicated that the two acyl groups of 2-MCPD-1,3-dioleate were smoothly hydrolyzed by pancreatic lipase and pancreatin to give free 2-MCPD. In contrast, the hydrolysis of 3-MCPD-1,2-dioleate proceeded predominantly at the primary position to produce 3-MCPD-2-oleate. 2-MCPD-1-oleate and 3-MCPD-1-oleate were further hydrolyzed to free 2- and 3-MCPD by pancreatic lipase and pancreatin, although the hydrolysis of 3-MCPD-2-oleate was 80 % slower than that of 3-MCPD-1-oleate. The intestinal absorption characteristics of these compounds were evaluated in vitro using a Caco-2 cell monolayer. The results revealed that the MCPD monooleates, but not the MCPD dioleates, were hydrolyzed to produce the free MCPD in the presence of the Caco-2 cells. The resulting free MCPD permeated the Caco-2 monolayer most likely via a diffusion mechanism because their permeation profiles were independent of the dose. Similar permeation profiles were obtained for 2- and 3-MCPDs.

  10. Oleyl alcohol inhibits intestinal long-chain fatty acid absorption in rats.

    PubMed

    Murota, K; Kawada, T; Matsui, N; Sakakibara, M; Takahashi, N; Fushiki, T

    2000-12-01

    Long-chain fatty acids are important nutrients, but obesity is the most common nutritional disorder in humans. In this study we investigated the effect of oleyl alcohol on the intestinal long-chain fatty acid absorption in rats. We administered [14C]oleic acid and oleyl alcohol as lipid emulsion intraduodenally in unanesthetized lymph-cannulated rats and measured the lymphatic output of oleic acid. Second, we orally administered lipid emulsion with a stomach tube and measured the luminal and mucosal oleic acid residues. Furthermore, rats were fed oleyl alcohol as a dietary component for 20 days, and fecal lipid and the weight of adipose tissues were measured. In lymph-cannulated rats, triglyceride and [14C]oleic acid output in the lymph were significantly lower in the presence of oleyl alcohol when compared with the absence of oleyl alcohol in a dose-dependent manner. The radioactivity remaining in the intestinal lumen was more strongly detected in rats that had been orally administered oleyl alcohol than in the controls. The feces of rats fed an oleyl-alcohol-added diet contained much higher amounts of lipids, and the weights of their adipose tissues were significantly lower than in the control group. These results suggest that oleyl alcohol inhibits the rat gastrointestinal absorption of long-chain fatty acids in vivo.

  11. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

    PubMed

    Aslam, Mohamad F; Frazer, David M; Faria, Nuno; Bruggraber, Sylvaine F A; Wilkins, Sarah J; Mirciov, Cornel; Powell, Jonathan J; Anderson, Greg J; Pereira, Dora I A

    2014-08-01

    The ferritin core is composed of fine nanoparticulate Fe(3+) oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe(3+) polyoxohydroxide (nanoFe(3+)). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe(2+) sulfate (FeSO4), nanoFe(3+), or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe(3+) was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe(3+) are equally bioavailable in WT mice, and at wk 8 the mean ± SEM hemoglobin increase was 18 ± 7 g/L in the FeSO4 group and 30 ± 5 g/L in the nanoFe(3+) group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe(3+) is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.

  12. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids☆

    PubMed Central

    Harrison, Earl H.

    2012-01-01

    Vitamin A is an essential nutrient for humans and is converted to the visual chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in animal-derived foods is found as long chain acyl esters of retinol and these are digested to free fatty acids and retinol before uptake by the intestinal mucosal cell. The retinol is then reesterified to retinyl esters for incorporation into chlylomicrons and absorbed via the lymphatics or effluxed into the portal circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids such as β-carotene are found in plant-derived foods. These and other carotenoids are transported into the mucosal cell by scavenger receptor class B type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by oxygenase and reductase enzymes and the retinol so produced is available for absorption via the two pathways described above. The efficiency of vitamin A and carotenoid intestinal absorption is determined by the regulation of a number of proteins involved in the process. Polymorphisms in genes for these proteins lead to individual variability in the metabolism and transport of vitamin A and carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. PMID:21718801

  13. Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese.

    PubMed

    Shawki, Ali; Anthony, Sarah R; Nose, Yasuhiro; Engevik, Melinda A; Niespodzany, Eric J; Barrientos, Tomasa; Öhrvik, Helena; Worrell, Roger T; Thiele, Dennis J; Mackenzie, Bryan

    2015-10-15

    Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and (54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of (59)Fe was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.

  14. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

    PubMed

    Lesjak, Marija; Hoque, Rukshana; Balesaria, Sara; Skinner, Vernon; Debnam, Edward S; Srai, Surjit K S; Sharp, Paul A

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.

  15. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  16. Regional distribution and variation of gamma-globulin absorption from the small intestine of the neonatal calf

    SciTech Connect

    Fetcher, A.; Gay, C.C.; McGuire, T.C.; Barbee, D.D.; Parish, S.M.

    1983-11-01

    125I-labeled immunoglobulin (Ig)G1 in colostral whey was used to determine the region of maximum absorption of Ig from the small intestine of the neonatal calf and the variation in Ig absorption among calves at the intestinal level. In experiment 1, 5 segments (approx 5%, 35%, 60%, 80%, and 95% of the duodenocecal length) were formed in the small intestine of 9 colostrum-deprived calves shortly after birth. These segments were injected with colostral whey containing 125I-IgG1 4 hours after birth, and uptake, transfer, and absorption (defined as uptake plus transfer) were determined for each segment 2 hours later. Raw data were adjusted for the milligrams of IgG1 injected per gram of intestinal tissue to obtain the least squares mean (LSM) value. The LSM values for absorption of IgG1 from distal segments 3, 4, and 5 were significantly greater (P less than 0.05) than those values for proximal segments 1 and 2. The region of the maximum IgG1 absorption was the lower small intestine, 60% to 80% of the duodenocecal length. There was also an indication of independence between uptake and transfer in each of the segments. Significant differences (P less than 0.05) were present among calves in the LSM values for uptake and absorption, but not for transfer. In experiment 2, thoracic ducts of 8 newborn calves were cannulated 4 to 5 hours after birth. At 6 hours after birth, colostral whey with 125I-IgG1 was injected into an intestinal segment (approx 60% to 80% of the duodenocecal length).

  17. Increased intestinal endotoxin absorption during enteric nematode but not protozoal infections through a mast cell-mediated mechanism.

    PubMed

    Farid, Ayman Samir; Jimi, Fumiko; Inagaki-Ohara, Kyoko; Horii, Yoichiro

    2008-06-01

    It is known that hypersensitivity reactions in the gastrointestinal tract, which are primarily mediated by mast cells, are associated with a secretory response of the epithelium and often increased permeability to macromolecules. Studies to date have not examined the effects of hyperpermeability on the absorption of toxic substances normally present in the intestinal lumen such as bacterial LPS. In the present study, we observed that Strongyloides venezuelensis infection in mice decreases the mRNA expression of intestinal epithelial cell junctional molecules (occludin and zonula occludens 1) and increases portal endotoxin levels 4 h after intragastric administration of LPS (20 mg/kg body weight). Furthermore, an increase in the flux of immunoglobulin G into the intestinal lumen was observed 10 days postinfection (PI). An increased rate of LPS absorption was also seen in mice infected with Nippostrongylus brasiliensis on day 14 PI and rats concurrently infected with S. venezuelensis and N. brasiliensis on day 20 PI. On the other hand, infection with Eimeria vermiformis and Eimeria pragensis was not observed to enhance LPS absorption 4 h after intragastric administration of LPS (20 mg/kg body weight), although E. vermiformis infection did inhibit the epithelial cell mRNA expression of zonula occludens 1, but not occludin, on day 9 PI, resulting in a reduced immunoglobulin G flux than that produced by S. venezuelensis infection. Our results suggest that mastocytosis accompanying intestinal nematode infection increases the intestinal absorption of LPS into the portal circulation by suppressing the expression of tight junction molecules.

  18. P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats.

    PubMed

    Liu, Hongming; Sun, Hua; Wu, Zhufeng; Zhang, Xingwang; Wu, Baojian

    2014-08-01

    1. The promising anticancer agent SNX-2112 (a novel Hsp90 inhibitor) is poorly bioavailable after oral administration. Here, we aim to determine the role of P-glycoprotein (P-gp) in the intestinal absorption of SNX-2112. 2. We found that SNX-2112 significantly stimulated P-gp ATPase activity in in vitro ATPase assay with a small EC50 (the half-maximal effective concentration) value of 0.32 µM. 3. In the single-pass perfused rat intestine model, absorption of SNX-2112 was not favored in the small intestine with a [Formula: see text] (the wall permeability) value of 0.38-0.64. By contrast, the compound was well absorbed in the colon with a [Formula: see text] value of 1.19. The P-gp inhibitors cyclosporine and elacridar (i.e. GF120918A) markedly enhanced SNX-2112 absorption in all four intestinal segments (i.e. duodenum, jejunum, ileum and colon) and the fold change ranged from 3.1 to 14.1. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of SNX-2112 by a 2.5-fold after oral administration. 4. This is the first report that P-gp-mediated efflux is a limiting factor for intestinal absorption of SNX-2112 in rats.

  19. Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption.

    PubMed

    Annaert, Pieter; Brouwers, Joachim; Bijnens, Ann; Lammert, Frank; Tack, Jan; Augustijns, Patrick

    2010-01-31

    The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, while the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults.

  20. Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine.

    PubMed

    Ito, Yukako; Venkatesan, Natarajan; Hirako, Noriko; Sugioka, Nobuyuki; Takada, Kanji

    2007-06-07

    Erythropoietin (EPO) loaded carbon nanotubes (CNTs) with surfactant as an absorption enhancer were prepared for the oral delivery of EPO using two types of CNTs, long and short fiber length CNTs, and the effect of CNT fiber length on the absorption efficiency of EPO was studied. After Labrasol, PEG-8 caprylic/capric glycerides, as absorption enhancer was adsorbed into long fiber CNTs of which mean fiber length was 20-80 microm, as a carrier, EPO and casein as protease inhibitor and Explotab (sodium starch glycolate) as a disintegrating agent, were mixed. The resulting solid preparation was administered into the rat jejunum and serum EPO levels were measured by ELISA. The dose of EPO, CNTs, casein and Explotab were 100 IU/kg, 5mg/kg, 25mg/kg and 2.5mg/kg, respectively. Serum EPO level reached to C(max), 69.0+/-3.9 mIU/ml, at 3.5+/-0.1h and AUC was 175.7+/-13.8 mIU h/ml. These values were approximately half of that obtained with short fiber length CNTs of which C(max) was 143.1+/-15.2 mIU/ml and AUC was 256.3+/-9.7 mIU h/ml. When amphoteric surfactant, Lipomin LA, sodium beta-alkylaminopropionic acid, was used to accelerate the disaggregation of long fiber length CNTs, C(max) was 36.0+/-4.9 and AUC was 96.9+/-11.9, which showed less bioavailability (BA) of EPO. These results suggest that the short fiber length CNTs deliver more both EPO and absorption enhancer to the absorptive cells of the rat small intestine and the aggregation of CNTs is not the critical factor for the oral delivery of EPO.

  1. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption.

    PubMed

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P

    2015-09-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.

  2. HPLC analysis of in vivo intestinal absorption and oxidative metabolism of salicylic acid in the rat.

    PubMed

    Kuzma, Mónika; Nyúl, Eszter; Mayer, Mátyás; Fischer, Emil; Perjési, Pál

    2016-12-01

    In vivo absorption and oxidative metabolism of salicylic acid in rat small intestine was studied by luminal perfusion experiment. Perfusion through the lumen of proximal jejunum with isotonic medium containing 250 μm sodium salicylate was carried out. Absorption of salicylate was measured by a validated HPLC-DAD method which was evaluated for a number of validation characteristics (specificity, repeatability and intermediate precision, limit of detection, limit of quantification, linearity and accuracy). The method was linear over the concentration range 0.5-50 μg/mL. After liquid-liquid extraction of the perfusion samples oxidative biotransformation of salicylate was also investigated by HPLC-MS. The method was linear over the concentration range 0.25-5.0 μg/mL. Two hydroxylated metabolites of salicylic acid (2,5-dihydroxybenzoic acid and 2,3-dihydroxybenzoic acid) were detected and identified. The mean recovery of extraction was 72.4% for 2,3-DHB, 72.5% for 2,5-DHB and 50.1% for salicylic acid, respectively. The methods were successfully applied to investigate jejunal absorption and oxidative metabolism of sodium salicylate in experimental animals. The methods provide analytical background for further metabolic studies of salycilates under modified physiological conditions.

  3. The Relation between Peristaltic and Segmental Contraction, Mixing, and Absorption in the Small Intestine

    NASA Astrophysics Data System (ADS)

    Banco, Gino; Brasseur, James; Wang, Yanxing; Ailiani, Amit; Neuberger, Thomas; Webb, Andrew

    2009-11-01

    The physiology and mechanics of the small intestine originates with lumen-scale fluid motions generated by enterically controlled muscle wall contractions. Although complex in appearance, we have shown with principle component decomposition of gut motion from a rat model that simpler component structure may integrate to produce basic peristaltic and segmental motions. To couple these measured modes with fluid mixing and nutrient absorption we have developed 2-D and axisymmetric models of the gut using the lattice-Boltzmann framework with scalar and second order moving boundary conditions. Previous models indicated that peristalsis is detrimental to absorption and therefore that gut motility is likely bimodal, transitioning between peristalsis and segmental modes to optimize the transport of chyme vs. nutrient absorption. However we have since discovered that more complex control is possible due to potential transitions between ``trapped'' vs. ``nontrapped'' peristaltic fluid motions, depending on occlusion ratio. These transitions lead to an important distinction between 2-D and axisymmetric models and indicate that gut motility may be more finely controlled than previously thought. [Supported by NSF

  4. A mechanism-based approach for absorption modeling: the Gastro-Intestinal Transit Time (GITT) model.

    PubMed

    Hénin, Emilie; Bergstrand, Martin; Standing, Joseph F; Karlsson, Mats O

    2012-06-01

    Absorption models used in the estimation of pharmacokinetic drug characteristics from plasma concentration data are generally empirical and simple, utilizing no prior information on gastro-intestinal (GI) transit patterns. Our aim was to develop and evaluate an estimation strategy based on a mechanism-based model for drug absorption, which takes into account the tablet movement through the GI transit. This work is an extension of a previous model utilizing tablet movement characteristics derived from magnetic marker monitoring (MMM) and pharmacokinetic data. The new approach, which replaces MMM data with a GI transit model, was evaluated in data sets where MMM data were available (felodipine) or not available (diclofenac). Pharmacokinetic profiles in both datasets were well described by the model according to goodness-of-fit plots. Visual predictive checks showed the model to give superior simulation properties compared with a standard empirical approach (first-order absorption rate + lag-time). This model represents a step towards an integrated mechanism-based NLME model, where the use of physiological knowledge and in vitro–in vivo correlation helps fully characterize PK and generate hypotheses for new formulations or specific populations.

  5. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.

    PubMed

    Ma, Jing; Chang, Jessica; Checklin, Helen L; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2010-09-01

    It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0.9% saline) or control (0.9% saline) at 4 ml/min for 150 min (T = - 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2.5 %), were co-infused intraduodenally (T = 0-120 min; 4.2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P < 0.005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.

  6. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    PubMed

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters.

  7. Effects of borneol on the intestinal transport and absorption of two P-glycoprotein substrates in rats.

    PubMed

    He, Huijuan; Shen, Qi; Li, Jian

    2011-07-01

    As the most prevalent route of delivery, oral administration has the challenge of potentially low bioavailability in part because P-glycoprotein (P-gp) in the intestinal tract affects absorption. Therefore, absorption enhancers or P-gp inhibitors are strategies to solve this problem. The aim of the present study was to investigate the effects of borneol on transportation of colchicine and rhodamine123, two P-gp substrates, in rats. In vitro transportation was assessed with a diffusion chamber system with isolated rat intestines. Different concentrations of borneol (10, 40 and 80 μg/mL) were prepared in solutions with two P-gp substrates compared with blank solutions. The in vivo effects on colchicine were assessed by a pharmacokinetic study. Borneol enhanced the absorptive transport of two P-gp substrates, which was relevant to the concentration. A pharmacokinetic study showed that in the presence of borneol, a significant increase in C(max) and AUC(0→8) of colchicine occurred when compared to colchicine alone. The study showed that borneol affected two P-gp substrates in the intestine, possibly by inhibiting the effects of P-gp and enhancing intestinal absorption of drugs. Therefore, borneol could be developed as a P-gp inhibitor and absorptive enhancer.

  8. Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth

    PubMed Central

    Simon, Trang; Cook, Victoria R.; Rao, Anuradha; Weinberg, Richard B.

    2011-01-01

    Apolipoprotein A-IV (apoA-IV) is synthesized by intestinal enterocytes during lipid absorption and secreted into lymph on the surface of nascent chylomicrons. A compelling body of evidence supports a central role of apoA-IV in facilitating intestinal lipid absorption and in regulating satiety, yet a longstanding conundrum is that no abnormalities in fat absorption, feeding behavior, or weight gain were observed in chow-fed apoA-IV knockout (A4KO) mice. Herein we reevaluated the impact of apoA-IV expression in C57BL6 and A4KO mice fed a high-fat diet. Fat balance and lymph cannulation studies found no effect of intestinal apoA-IV gene expression on the efficiency of fatty acid absorption, but gut sac transport studies revealed that apoA-IV differentially modulates lipid transport and the number and size of secreted triglyceride-rich lipoproteins in different anatomic regions of the small bowel. ApoA-IV gene deletion increased expression of other genes involved in chylomicron assembly, impaired the ability of A4KO mice to gain weight and increase adipose tissue mass, and increased the distal gut hormone response to a high-fat diet. Together these findings suggest that apoA-IV may play a unique role in integrating feeding behavior, intestinal lipid absorption, and energy storage. PMID:21840868

  9. Viable, lyophilized lactobacilli do not increase iron absorption from a lactic acid-fermented meal in healthy young women, and no iron absorption occurs in the distal intestine.

    PubMed

    Bering, Stine; Sjøltov, Laila; Wrisberg, Seema S; Berggren, Anna; Alenfall, Jan; Jensen, Mikael; Højgaard, Liselotte; Tetens, Inge; Bukhave, Klaus

    2007-11-01

    Lactic acid-fermented foods have been shown to increase Fe absorption in human subjects, possibly by lowering pH, activation of phytases, production of organic acids, or by the viable lactic acid bacteria. In this study the effect of a heat-inactivated lactic acid-fermented oat gruel with and without added viable, lyophilized Lactobacillus plantarum 299v on non-haem Fe absorption was investigated. Furthermore, Fe absorption in the distal intestine was determined. In a randomized, double-blinded crossover trial eighteen healthy young women aged 22 (SD 3) years with low Fe status (serum ferritin < 30 microg/l) were served the two test gruels, extrinsically labelled with 59Fe and served with two enterocoated capsules (containing 55Fe(II) and 55Fe(III), respectively) designed to disintegrate in the ileum. The meals were consumed on two consecutive days, e.g. in the order AA followed by BB in a second period. Non-haem Fe absorption was determined from 59Fe whole-body retention and isotope activities in blood samples. The concentrations of Fe, lactate, phytate, and polyphenols, and the pH were similar in the heat-inactivated lactic acid-fermented oat gruels with and without added L. plantarum 299v, and no difference in Fe absorption was observed between the test gruels (1.4 and 1.3%, respectively). Furthermore, no absorption of Fe in the distal intestine was observed. In conclusion, addition of viable, lyophilized lactobacillus to a heat-inactivated lactic acid-fermented oat gruel does not affect Fe absorption, and no absorption seems to occur in the distal part of the intestine from low Fe bioavailability meals in these women.

  10. [Rat intestine absorption kinetics study on cucurbitacin B-sodium deoxycholate/phospholipid mixed nanomicelles with in vitro everted gut sacs model].

    PubMed

    Cheng, Ling; Shen, Bao-de; Li, Juan-juan; Qiu, Ling; Shen, Gang; Zhang, Li-hong; Han, Jin; Yuan, Hai-long

    2015-07-01

    To investigate the absorption kinetics of Cu B-SDC/PLC-MMs in rat different intestinal segments and compared with the absorption of Cu B suspension. The in vitro everted gut sacs model was established to study the absorption characteristics of Cu B-SDC/ PLC-MMs in rat duodenum, jejunum, ileum and colon, and the content of cucurbitacin B was detected by HPLC method, and the effects of concentrations on intestinal absorption were evaluated as well. The results showed that the absorption of Cu B-SDC/PLC-MMs was linearity at different intestine segment and different concentrations (R2 > 0.9), which was consistent with zero order rate process. The Ka of different intestine segments showed a concentration-dependent increasing along with the raised concentration of Cu B-SDC/ PLC-MMs, indicating that it was likely to be a mechanism of passive absorption. The best absorption site of Cu B-SDC/PLC-MMs was ileum, and its absorptions in different intestinal segments were superior to cucurbitacin B suspension. SDC/PLC-MMs could significantly enhance the intestinal absorption of cucurbitacin B, and the study of intestinal absorption kinetics of Cu B-SDC/PLC-MMs had gave a support to its further reasonable solidfication.

  11. Oxalate catabolism in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalic acid is found in most plant species and can serve beneficial roles that protect the plant from a variety of environmental stresses. Excessive amounts of oxalate, however, can be detrimental to plant health. Thus, careful coordination of oxalate metabolism is needed. Despite the important impa...

  12. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status.

    PubMed

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-08-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2 D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m(2)). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2 D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = -0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to

  13. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status

    PubMed Central

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m2). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = −0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to the decline in BMD after RYGB, and strategies to

  14. Gastric emptying and intestinal absorption of ingested water and saline by hypovolemic rats.

    PubMed

    Stricker, Edward M; Bykowski, Michael R; Hossler, Carrie A Smith; Curtis, Kathleen S; Smith, James C

    2009-12-07

    Recent experiments showed that in a one-bottle test conducted 16h after sc injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water or 0.30 M NaCl in an initial drinking episode but did not empty the ingested fluid from the stomach or absorb it from the small intestine very rapidly, certainly not as rapidly as when 0.15M NaCl was consumed (Smith et al., Am J Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of water and 0.30 M NaCl ingestion and the movement of consumed fluid through the gastrointestinal tract when PEG-treated rats were given a two-bottle delayed-access test. We found that both fluids always were consumed in the first drinking episode, that the fluid mixture ingested was equivalent to 0.10-0.15M NaCl, and that gastric emptying rate and net fluid absorption from the small intestine usually were much faster than when PEG-treated rats drank either water or hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic rats in the same episode adaptively facilitated the movement into the circulation of a near-isotonic fluid that is ideal for restoring plasma volume deficits.

  15. Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine.

    PubMed

    Barrand, M A; Callingham, B A; Hider, R C

    1987-03-01

    The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-ligand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 micrograms dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7-700 micrograms, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7-70 micrograms but not at 700 micrograms suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition.

    PubMed

    Alqahtani, Saeed; Qosa, Hisham; Primeaux, Brian; Kaddoumi, Amal

    2015-09-05

    The known mechanism by which orlistat decreases the absorption of dietary cholesterol is by inhibition of intestinal lipases. The aim of this study was to investigate the ability of orlistat to limit cholesterol absorption by inhibition of the cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) as another mechanism of action. In situ rat intestinal perfusion studies were conducted to study the effect of orlistat on jejunal cholesterol absorption. Inhibition kinetic parameters were calculated from in vitro inhibition studies using Caco2 and NPC1L1 transfected cell lines. The in situ studies demonstrated that intestinal perfusion of orlistat (100µM) was able to reduce cholesterol absorption by three-fold when compared to control (i.e. in the absence of orlistat, P<0.01). In vitro studies using Caco2 cells demonstrated orlistat to reduce the cellular uptake of cholesterol by 30%. Additionally, orlistat reduced the cellular uptake of cholesterol in dose dependent manner in NPC1L1 transfected cell line with an IC50=1.2µM. Lineweaver-Burk plot indicated a noncompetitive inhibition of NPC1L1 by orlistat. Beside the already established mechanism by which orlistat reduces the absorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein.

  17. Effects of intraluminal hydrostatic pressure on L-methionine absorption in the obstructed small intestine of the rat

    SciTech Connect

    Enochsson, L.; Nylander, G.

    1986-03-01

    The effects of elevated intraluminal hydrostatic pressure on the active absorption of the amino acid selenium 75 L-methionine has been analyzed in the normal and obstructed small intestine. An intestinal loop of defined position and length was included in a recircling perfusion system from which the elimination rate of the radiolabeled amino acid was measured. Preset pressure levels within the system were maintained by a servo-controlled unit, which added or subtracted volume to keep the pressure constant. The rate of amino acid elimination increased when the nonobstructed loop was subjected to a pressure of 10 cm H2O but decreased when exposed to 20cm H2O. Using a loop of intestine subjected to 48 hours of obstruction, amino acid elimination was greatly retarded compared with that of the nonobstructed loop. By increasing the intraluminal pressure to 10 and 20 cm H2O, the elimination rate increased, equalling that of the nonobstructed gut. The results suggest that intestinal obstruction per se decreases active absorption secondary to impaired intestinal viability. Moderately increased intraluminal pressure adds a driving force to L-methionine absorption, the mechanism of which is obscure.

  18. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  19. Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.

    PubMed

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam

    2016-01-15

    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption.

  20. Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicor...

  1. Optimization of the Caco-2 permeability assay to screen drug compounds for intestinal absorption and efflux.

    PubMed

    Press, Barry

    2011-01-01

    In vitro permeability assays are a valuable tool for scientists during lead compound optimization. As a majority of discovery projects are focused on the development of orally bioavailable drugs, correlation of in vitro permeability data to in vivo absorption results is critical for understanding the structural-physicochemical relationship (SPR) of drugs exhibiting low levels of absorption. For more than a decade, the Caco-2 screening assay has remained a popular, in vitro system to test compounds for both intestinal permeability and efflux liability. Despite advances in artificial membrane technology and in silico modeling systems, drug compounds still benefit from testing in cell-based epithelial monolayer assays for lead optimization. This chapter provides technical information for performing and optimizing the Caco-2 assay. In addition, techniques are discussed for dealing with some of the most pressing issues surrounding in vitro permeability assays (i.e., low aqueous solubility of test compounds and low postassay recovery). Insights are offered to help researchers avoid common pitfalls in the interpretation of in vitro permeability data, which can often lead to the perception of misleading results for correlation to in vivo data.

  2. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    NASA Astrophysics Data System (ADS)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  3. Lipid absorption defects in intestine-specific microsomal triglyceride transfer protein and ATP-binding cassette transporter A1-deficient mice.

    PubMed

    Iqbal, Jahangir; Parks, John S; Hussain, M Mahmood

    2013-10-18

    We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92-95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations.

  4. Luminal Glucose Does Not Enhance Active Intestinal Calcium Absorption in mice: Evidence Against a Role for Cav1.3 as a Mediator of Calcium Uptake During Absorption

    PubMed Central

    Reyes-Fernandez, Perla C.; Fleet, James C.

    2015-01-01

    Intestinal Ca absorption occurs through a 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels following a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine week-old male C57BL/6J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), Calbindin D9k (CaBPD9k) and Cav1.3 mRNA levels were measured in the duodenum, jejunum and ileum. TRPV6 and CaBPD9k expression were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs while Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (p=0.003), serum 1,25(OH)2D3 (p<0.001) and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (p=0.6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo. PMID:26403486

  5. Intestinal nutrient absorption - A biomarker for deleterious heavy metals in aquatic environments

    SciTech Connect

    Farmanfarmaian, A. )

    1988-09-01

    The deleterious effects of heavy metals on absorptive processes at the membrane surface will be summarized. Among the deleterious heavy metal chlorides (HgCl{sub 2}, CH{sub 3}HgCl, CdCl{sub 2}, CoCl{sub 2}, SrCl{sub 2}) tested HgCl{sub 2}, CH{sub 3}HgCl, and CdCl{sub 2} inhibit the absorption of several amino acids and sugars (L-leucine, L-methionine, L-isoleucine, L-lysine, cyclolencine, D-glucose, and D-galactose). The dose dependent inhibition of L-leucine uptake by HgCl{sub 2} is shown in a number of fish from different collection sites representing nektonic plankton feeders as well as demersal carnivores. The same type of data is shown for both HgCl{sub 2} and HC{sub 3}HgCl in the case of the commercially important summer flounder. Since the overall rate of intestinal absorption of amino acids and sugars involves the three processes of simple diffusion, protein-mediated facilitated diffusions, and protein-mediated sodium dependent active transport, the inhibition of the overall rate may not be sensitive enough as a biomarker. However, the active component, which alone accumulates essential amino acids in the tissue, appears to be very sensitive and can be used as a biomarker. The terminal tissue-to-medium (T/M) ratio of L-leucine concentration shows a 2-3 fold accumulation in the absence of mercury. Since the diffusional components can at best equilibrate L-leucine across the membrane % inhibition of the active component can be calculated after subtracting 1 from the experimental T/M values. The resulting inhibition is very sever ranging from approximately 50-100% for HgCl{sub 2} and 20-70% for CH{sub 3}HgCl over a range of 5-20 ppm of mercury.

  6. Effect of giardiasis combined with low-protein diet on intestinal absorption of glucose and electrolytes in gerbils.

    PubMed

    Gomes, Maria Aparecida; de Oliveira, Dirce Ribeiro; de Freitas, Sabrina Emanuele; de Pinho Viana, Marcelo; Borges, Elizabeth Lage

    2012-08-01

    Studies have shown that symptomatic infection by Giardia lamblia causes acute or chronic diarrhea, dehydration, abdominal pain and malabsorption, leading to undernutrition and weight loss. The aim of the present study was to evaluate the effects of giardiasis and its combination with a low-protein diet on the intestinal absorption of glucose and electrolytes in gerbils. The intestinal absorption of glucose, sodium and potassium was investigated in male gerbils weighing 46-64 g (n≥5). A Tyrode solution containing twice the glucose, sodium and potassium concentration (pH 7.4) was infused through the intestinal loops for 40 min. Glucose absorption was not significantly affected by diet and infection. However, there was a significant increase in sodium absorption in the Giardia-infected group (57.2±6.1, p<0.05) in comparison to the control, low-protein diet and low-protein diet+Giardia-infected groups (8.9±6.5, 2.8±11.1 and 0.8±7.9, respectively; p<0.05). Moreover, potassium was absorbed in the Giardia-infected group (0.45±0.30), while the other groups exhibited potassium secretion. A low-protein diet and Giardia infection had no influence over glucose absorption. However, Giardia infection increased sodium and potassium uptake, suggesting a compensatory mechanism for maintaining homeostasis after likely hypernatremia and hypokalemia caused by the diarrhea that accompanies giardiasis.

  7. Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption

    NASA Astrophysics Data System (ADS)

    Verma, Rajeshwar P.; Hansch, Corwin; Selassie, Cynthia D.

    2007-01-01

    Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials. The present study provides comparative QSAR analysis on PAMPA/modified PAMPA for high throughput profiling of drugs with respect to Caco-2 cells and human intestinal absorption.

  8. The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

    SciTech Connect

    Laftah, A.H.; Simpson, R.J. Peters, T.J.; Raja, K.B.

    2008-06-15

    The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption.

  9. Characterization of intestinal absorption of quinidine, a P-glycoprotein substrate, given as a powder in rats.

    PubMed

    Mori, N; Iwamoto, H; Yokooji, T; Murakami, T

    2012-05-01

    The characteristics of intestinal absorption of quinidine, a P-glycoprotein (P-gp) substrate in biopharmaceutics classification system (BCS) Class I, after oral administration as a powder in No. 9 HPMC capsule (diameter 2.6 mm; length 8.4 mm, volume 25 microl) was examined in rats from the following viewpoints: (i) main absorption site of quinidine, (ii) effect of dosage amounts (or luminal concentrations) of quinidine (10 mg vs 0.1 mg/kg), (iii) contribution of P-gp in quinidine absorption (0.1 mg/kg), and (iv) effect of gastric pH on quinidine absorption. Quinidine administered orally at a dose of 10 mg/kg was discharged from the stomach steadily with time and disappeared rapidly from the proximal intestine, where P-gp expression was low. In contrast, quinidine administered at a dose of 0.1 mg/kg remained longer in the gastrointestinal lumen than that administered at a dose of 10 mg/kg. The pretreatment with cyclosporine A, a P-gp inhibitor, greatly increased the intestinal absorption of quinidine given at a dose of 0.1 mg/kg. The gastric pH in untreated control rats was pH 3.6, and the treatment with ranitidine (10mg/kg, ip), a H2 blocker, increased to pH 6.4. The recovered amounts of quinidine 30 min after administration were 21.1% of dose in control rats and 94.7% in ranitidine-treated rats. The value of plasma AUC(0-6h) of quinidine in ranitidine-treated rats was about 40% that in untreated control rats. In conclusion, quinidine was rapidly and efficiently absorbed at the proximal intestine under ordinary circumstances. However, the oral bioavailability was modulated by various factors including the dose (or luminal concentration at the absorption site), presence of P-gp inhibitors, and gastrointestinal pH.

  10. Pinolenic Acid in Structured Triacylglycerols Exhibits Superior Intestinal Lymphatic Absorption As Compared to Pinolenic Acid in Natural Pine Nut Oil.

    PubMed

    Chung, Min-Yu; Woo, Hyunjoon; Kim, Juyeon; Kong, Daecheol; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2017-03-01

    The positional distribution pattern of fatty acids (FAs) in the triacylglycerols (TAGs) affects intestinal absorption of these FAs. The aim of this study was to compare lymphatic absorption of pinolenic acid (PLA) present in structured pinolenic TAG (SPT) where PLA was evenly distributed on the glycerol backbone, with absorption of pine nut oil (PNO) where PLA was predominantly positioned at the sn-3 position. SPT was prepared via the nonspecific lipase-catalyzed esterification of glycerol with free FA obtained from PNO. Lymphatic absorption of PLA from PNO and from SPT was compared in a rat model of lymphatic cannulation. Significantly (P < 0.05) greater amounts of PLA were detected in lymph collected for 8 h from an emulsion containing SPT (28.5 ± 0.7% dose) than from an emulsion containing PNO (26.2 ± 0.6% dose), thereby indicating that PLA present in SPT has a greater capacity for lymphatic absorption than PLA from PNO.

  11. Influence of prolactin and calcium gluconate concentration on permeation and intestinal absorption of Ca(II) ions.

    PubMed

    Ryszka, Florian; Klimas, Rimantas; Dolinska, Barbara; Lopata, Katarzyna

    2012-08-01

    The in vitro permeation and absorption of calcium ions across the small intestine were measured at different concentrations of calcium gluconate solutions (1.0, 10.0 and 20.0 mM) with or without prolactin. The calcium ions permeated through the small intestine from a donor environment to an acceptor environment that mimicked the conditions in the stomach to ileum segment of the digestive tract. The permeation and absorption of calcium were directly dependent on the calcium concentration of the solutions. At 10 and 20 mM permeation was significantly higher than that at 1.0 mM (p < 0.05). In the presence of prolactin both permeation and absorption increase considerably. At the lowest concentration (1.0 mM) simulating calcium deficiency, there was compensation by the small intestine, suggesting that such deficiency stimulates its mobilization from intestinal tissue. Prolactin enhances the calcium mobilization process even at sufficient calcium intakes. It is suggested that prolactin takes part in regulation of calcium homeostasis in the organism.

  12. Mechanisms underlying the effects of inulin-type fructans on calcium absorption in the large intestine of rats.

    PubMed

    Raschka, Ladislav; Daniel, Hannelore

    2005-11-01

    Inulin-type fructans (inulin, oligofructose, fructooligosaccharides) in the diet do increase intestinal calcium absorption in animals and humans, but the underlying mechanism has not been identified. We therefore assessed the effects of fermentation of inulin-type fructans on transepithelial calcium transport in rat large intestine. Transepithelial calcium fluxes in vitro (Ussing chamber), effects on gene expression, mucosal morphology, and composition of luminal contents were determined in rats fed a standard diet and/or a diet containing 10% (w/w) 1/1 inulin-oligofructose mixture (INOF). Net transepithelial calcium transport in large intestine of rats fed a standard diet was increased by high mucosal calcium concentrations, the presence of 100 mmol/L mucosal short-chain fatty acids (SCFAs), the presence of 10 g/L INOF at the mucosal side, but not by reducing mucosal pH. Tissues from rats fed INOF did not show altered calcium transport when compared to controls. However, when flux data were based on the total caecal surface area, INOF-fed rats nearly doubled absorption rate in caecum. INOF feeding altered transcript levels of several mucosal genes that can be linked to transcellular and paracellular calcium transport processes. In addition, a decreased luminal pH in caecum with markedly increased caecal pools of total, soluble, and ionized calcium resulted from INOF ingestion. Thus, inulin-type fructans increase the large intestinal calcium absorption by different mechanisms including enhanced pools of soluble and ionized calcium, an increase in the absorptive surface predominantly in caecum, the increased concentrations of SCFAs, and by direct interaction with the intestinal tissue.

  13. [Analysis and comparison of intestinal absorption of components of Gegenqinlian decoction in different combinations based on pharmacokinetic parameters].

    PubMed

    Zhang, Yi-Zhu; An, Rui; Yuan, Jin; Wang, Yue; Gu, Qing-Qing; Wang, Xin-Hong

    2013-10-01

    To analyse and compare the characteristics of the intestinal absorption of puerarin, baicalin, berberine and liquiritin in different combinations of Gegenqinlian decoction based on pharmacokinetic parameters, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was applied for the quantification of four components in rat's plasma. And pharmacokinetic parameters were determined from the plasma concentration-time data with the DAS software package. The influence of different combinations on pharmacokinetics of four components was studied to analyse and compare the absorption difference of four components, together with the results of the in vitro everted gut model and the rat single pass intestinal perfusion model. The results showed that compared with other combinations, the AUC values of puerarin, baicalin and berberine were increased significantly in Gegenqinlian decoction group, while the AUC value of liquiritin was reduced. Moreover, the absorption of four components was increased significantly supported by the results from the in vitro everted gut model and the rat single pass intestinal perfusion model, which indicated that the Gegenqinlian decoction may promote the absorption of four components and accelerate the metabolism of liquiritin by the cytochrome P450.

  14. Water absorption and bicarbonate secretion in the intestine of the sea bream are regulated by transmembrane and soluble adenylyl cyclase stimulation.

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Power, Deborah M; Canário, Adelino V M; Fuentes, Juan

    2012-12-01

    In the marine fish intestine luminal, HCO₃⁻ can remove divalent ions (calcium and magnesium) by precipitation in the form of carbonate aggregates. The process of epithelial HCO₃⁻ secretion is under endocrine control, therefore, in this study we aimed to characterize the involvement of transmembrane (tmACs) and soluble (sACs) adenylyl cyclases on the regulation of bicarbonate secretion (BCS) and water absorption in the intestine of the sea bream (Sparus aurata). We observed that all sections of sea bream intestine are able to secrete bicarbonate as measured by pH-Stat in Ussing chambers. In addition, gut sac preparations reveal net water absorption in all segments of the intestine, with significantly higher absorption rates in the anterior intestine that in the rectum. BCS and water absorption are positively correlated in all regions of the sea bream intestinal tract. Furthermore, stimulation of tmACs (10 μM FK + 500 μM IBMX) causes a significant decrease in BCS, bulk water absorption and short circuit current (Isc) in a region dependent manner. In turn, stimulation of sACs with elevated HCO₃⁻ results in a significant increase in BCS, and bulk water absorption in the anterior intestine, an action completely reversed by the sAC inhibitor KH7 (200 μM). Overall, the results reveal a functional relationship between BCS and water absorption in marine fish intestine and modulation by tmACs and sAC. In light of the present observations, it is hypothesized that the endocrine effects on intestinal BCS and water absorption mediated by tmACs are locally and reciprocally modulated by the action of sACs in the fish enterocyte, thus fine-tuning the process of carbonate aggregate production in the intestinal lumen.

  15. Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues: theoretical development and applications

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Leesman, G. D.; Amidon, G. L.

    1993-01-01

    A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS).

  16. Digestion and absorption of sugars and sugar substitutes in rat small intestine.

    PubMed

    Tsuji, Y; Yamada, K; Hosoya, N; Moriuchi, S

    1986-02-01

    The bioavailability of newly developed sugar substitutes was observed by measuring the transmural potential difference (delta PD) evoked by Na+-dependent active transport of glucose, which is supposed to be produced by the hydrolysis of sugar substitutes. delta PD was measured using everted intestinal sac prepared from jejunum of adult rats and compared with the digestibility of sugar substitutes in the mucosal homogenate of everted sac. delta PDs evoked by glucose, maltose or maltosylfructose had almost the same levels, however, the delta PD evoked by sucrose was a little lower. delta PDs evoked by maltitol or palatinose were low, and delta PDs evoked by fructo-oligosaccharides were negligible. The hydrolyzing activities of these sugars and sugar substitutes by the mucosal homogenate were correlated with the delta PDs. A significant positive correlation was observed between delta PDmax of various sugars and sugar substitutes and the Vmax of their corresponding hydrolyzing activities. Also, a significant positive correlation was observed between Kt and Km values of these sugars. These results suggest that the absorption of sugar substitutes is dependent on digestibility by membrane digestive enzymes.

  17. Evaluation of Oxalate Concentration in the U.S. Spinach Germplasm Collection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In addition to its high nutrient content, spinach (Spinacia oleracea L.) is also known to have greater amount of oxalic acid than most crops. Oxalic acid may form crystals with minerals to reduce the bioavailability and absorption of calcium and iron in diets, and calcium oxalate may deposit in the...

  18. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo.

    PubMed Central

    Nøhr, Martha Kampp; Thale, Zia I; Brodin, Birger; Hansen, Steen H; Holm, René; Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin in Caco-2 cells. Oral coadministration of vigabatrin and infant formula significantly reduced Cmax and prolonged tmax of vigabatrin absorption. Ligands for the proton-coupled amino acid transporter PAT1, sarcosine, and proline/l-tryptophan had similar effects on the pharmacokinetic profile of vigabatrin. The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems reasonable that infant formula may also directly affect the intestinal absorption rate of vigabatrin possibly via PAT1. PMID:25505585

  19. Involvement of concentrative nucleoside transporter 1 in intestinal absorption of trifluorothymidine, a novel antitumor nucleoside, in rats.

    PubMed

    Okayama, Takashige; Yoshisue, Kunihiro; Kuwata, Keizo; Komuro, Masahito; Ohta, Shigeru; Nagayama, Sekio

    2012-02-01

    ααα-Trifluorothymidine (TFT), an anticancer nucleoside analog, is a potent thymidylate synthase inhibitor. TFT exerts its antitumor activity primarily by inducing DNA fragmentation after incorporation of the triphosphate form of TFT into the DNA. Although an oral combination of TFT and a thymidine phosphorylase inhibitor has been clinically developed, there is little information regarding TFT absorption. Therefore, we investigated TFT absorption in the rat small intestine. After oral administration of TFT in rats, more than 75% of the TFT was absorbed. To identify the uptake transport system, uptake studies were conducted by using everted sacs prepared from rat small intestines. TFT uptake was saturable, significantly reduced under Na(+)-free conditions, and strongly inhibited by the addition of an endogenous pyrimidine nucleoside. From these results, we suggested the involvement of concentrative nucleoside transporters (CNTs) in TFT absorption into rat small intestine. In rat small intestines, the mRNAs coding for rat CNT1 (rCNT1) and rCNT2, but not for rCNT3, were predominantly expressed. To investigate the roles of rCNT1 and rCNT2 in TFT uptake, we conducted uptake assays by using Xenopus laevis oocytes injected with rCNT1 complementary RNA (cRNA) and rCNT2 cRNA. TFT uptake by X. laevis oocytes injected with rCNT1 cRNA, and not rCNT2 cRNA, was significantly greater than that by water-injected oocytes. In addition, in situ single-pass perfusion experiments performed using rat jejunum regions showed that thymidine, a substrate for CNT1, strongly inhibited TFT uptake. In conclusion, TFT is absorbed via rCNT1 in the intestinal lumen in rats.

  20. The molecular mechanism of intestinal levodopa absorption and its possible implications for the treatment of Parkinson's disease.

    PubMed

    Camargo, Simone M R; Vuille-dit-Bille, Raphael N; Mariotta, Luca; Ramadan, Tamara; Huggel, Katja; Singer, Dustin; Götze, Oliver; Verrey, François

    2014-10-01

    Levodopa (L-DOPA) is the naturally occurring precursor amino acid for dopamine and the main therapeutic agent for neurologic disorders due to dopamine depletion, such as Parkinson's disease. l-DOPA absorption in small intestine has been suggested to be mediated by the large neutral amino acids transport machinery, but the identity of the involved transporters is unknown. Clinically, coadministration of l-DOPA and dietary amino acids is avoided to decrease competition for transport in intestine and at the blood-brain barrier. l-DOPA is routinely coadministered with levodopa metabolism inhibitors (dopa-decarboxylase and cathechol-O-methyl transferase inhibitors) that share structural similarity with levodopa. In this systematic study involving Xenopus laevis oocytes and Madin-Darby canine kidney epithelia expression systems and ex vivo preparations from wild-type and knockout mice, we identified the neutral and dibasic amino acids exchanger (antiporter) b(0,+)AT-rBAT (SLC7A9-SLC3A1) as the luminal intestinal l-DOPA transporter. The major luminal cotransporter (symporter) B(0)AT1 (SLC6A19) was not involved in levodopa transport. L-Leucine and L-arginine competed with levodopa across the luminal enterocyte membrane as expected for b(0,+)AT-rBAT substrates, whereas dopa-decarboxylase and cathechol-O-methyl transferase inhibitors had no effect. The presence of amino acids in the basolateral compartment mimicking the postprandial phase increased transepithelial levodopa transport by stimulating basolateral efflux via the antiporter LAT2-4F2 (SLC7A8-SLC3A2). Additionally, the aromatic amino acid uniporter TAT1 (SLC16A10) was shown to play a major role in l-DOPA efflux from intestinal enterocytes. These results identify the molecular mechanisms mediating small intestinal levodopa absorption and suggest strategies for optimization of delivery and absorption of this important prodrug.

  1. Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

    PubMed

    Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

    2015-12-01

    This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the P(app) and K(a) of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions.

  2. [Analysis of oxalic acid and oxalates].

    PubMed

    Leskovar, P

    1979-08-01

    It is reported on individual methods for the estimation of the oxalic acid in body fluids, particularly in the urine. The case in question is a survey of the oxalate estimation methods, which, however, has no pretensions to completeness. The at present most actualestimation methods are brought somewhat more in detail. The data are not sufficient for the laboratorytechnical performance of the individual methods, this would transgress the possibilities of the work. However, the original papers are cited which contain all the necessary details. Some technical difficulties and disturbances in the individual estimation methods are also entered. Despite excellent work of several teams the problems of standardization, of the absolutely reliable reference methoda as well as of an objective consideration of advantages and disadvantages of individual, often subjectively judged methods is not yet solved. Comparing these methods, one gets the impression that several reliable methods of the same value are established. It seems that this estimation method brings the greatest progress which will reliably establish so small quantities of oxalate as they are in the blood or in the liquor. By this also the oxalate clearance and the renal oxalate treatment becomes more exactly establishable than up to now.

  3. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.

    PubMed

    Takada, Tappei; Yamanashi, Yoshihide; Konishi, Kentaro; Yamamoto, Takehito; Toyoda, Yu; Masuo, Yusuke; Yamamoto, Hideaki; Suzuki, Hiroshi

    2015-02-18

    Vitamin K (VK) is a micronutrient that facilitates blood coagulation. VK antagonists, such as warfarin, are used in the clinic to prevent thromboembolism. Because VK is not synthesized in the body, its intestinal absorption is crucial for maintaining whole-body VK levels. However, the molecular mechanism of this absorption is unclear. We demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In vitro studies using NPC1L1-overexpressing intestinal cells and in vivo studies with Npc1l1-knockout mice revealed that intestinal VK absorption is NPC1L1-dependent and inhibited by ezetimibe, an NPC1L1-selective inhibitor clinically used for dyslipidemia. In addition, in vivo pharmacological studies demonstrated that the coadministration of ezetimibe and warfarin caused a reduction in hepatic VK levels and enhanced the pharmacological effect of warfarin. Adverse events caused by the coadministration of ezetimibe and warfarin were rescued by oral VK supplementation, suggesting that the drug-drug interaction effects observed were the consequence of ezetimibe-mediated VK malabsorption. This mechanism was supported by a retrospective evaluation of clinical data showing that, in more than 85% of warfarin-treated patients, the anticoagulant activity was enhanced by cotreatment with ezetimibe. Our findings provide insight into the molecular mechanism of VK absorption. This new drug-drug interaction mechanism between ezetimibe (a cholesterol transport inhibitor) and warfarin (a VK antagonist and anticoagulant) could inform clinical care of patients on these medications, such as by altering the kinetics of essential, fat-soluble vitamins.

  4. Role of 1,25-Dihydroxyvitamin D3 on Intestinal Phosphate Absorption in Rats with a Normal Vitamin D Supply

    PubMed Central

    Rizzoli, R.; Fleisch, H.; Bonjour, J-P.

    1977-01-01

    In vitamin D-deficient rats, impaired intestinal phosphorus (P) absorption can be corrected by 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]. In the present study, it was investigated whether changes in 1,25-(OH)2D3 production can influence intestinal P transport also in animals with a normal supply of vitamin D. The intestinal P absorption was evaluated in rats using both the in situ duodenal loop technique and the determination of the overall gastrointestinal absorption under three conditions known to influence the production of 1,25-(OH)2D3: (a) variation in dietary P, (b) thyroparathyroidectomy (TPTX) with or without administration of parathyroid hormone (PTH), and (c) treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). In all circumstances changes in duodenal absorption paralleled the changes in the overall fractional absorption. (a) Lowering dietary P stimulated P absorption. (b) TPTX decreased P absorption. This effect was corrected either by the administration of PTH or by the administration of 1,25-(OH)2D3. (c) EHDP, when given at a dose known to inhibit 1,25-(OH)2D3 formation, decreased the duodenal P absorption in both intact and TPTX animals. This effect was corrected by 1,25-(OH)2D3. In the TPTX-EHDP-treated animals, the administration of PTH did not rectify the low duodenal P absorption. These results support the thesis that, in rats with normal vitamin D supply, variations in the endogenous production of 1,25-(OH)2D3 change the rate of P absorption. However, these changes are in such magnitude that they are of relatively small importance when compared to the effect of variation in the dietary intake of P. These results also strongly suggest that the action of PTH on duodenal P transport is mediated by its effect on 1,25-(OH)2D3 production, inasmuch as the effect of the hormone is abolished after blocking the renal 1-hydroxylation with EHDP. PMID:893667

  5. The role of Niemann-Pick C1 - Like 1 (NPC1L1) in intestinal sterol absorption.

    PubMed

    Turley, Stephen D

    2008-04-01

    The absorption of cholesterol by the proximal small intestine represents a major pathway for the entry of cholesterol into the body pools. This cholesterol is derived primarily from the bile and the diet. In adult humans, typically several hundred milligrams of cholesterol reach the liver from the intestine daily, with the potential to impact the plasma low density lipoprotein-cholesterol (LDL-C) concentration. There are three main phases involved in cholesterol absorption. The first occurs intraluminally and culminates in micellar solubilization of unesterified cholesterol which facilitates its movement up to the brush border membrane (BBM) of the enterocyte. The second phase involves the transport of cholesterol across the BBM by Niemann-Pick C1 Like-1 (NPC1L1), while the third phase entails a series of steps within the enterocyte involving the esterification of cholesterol and its incorporation, along with other lipids and apolipoprotein B48 (apo B48), into nascent chylomicrons (CM). The discovery of the role of NPC1L1 in intestinal sterol transport occurred directly as a consequence of efforts to identify the molecular target of ezetimibe, a novel, potent, and specific inhibitor of sterol absorption that is now widely used in combination therapy with statins for the management of hypercholesterolemia in the general population. Some aspects of the role of NPC1L1 in cholesterol absorption nevertheless remain controversial and are the subject of ongoing research. For example, one report suggests that NPC1L1 is located not in the plasma membrane but intracellularly where it is thought to be involved in cytosolic trafficking of cholesterol, while another concludes that a protein other than NPC1L1 is responsible for the high affinity binding of cholesterol on intestinal BBM. However, other new studies which show that the in vivo responsiveness of different species to ezetimibe correlates with NPC1L1 binding affinity further support the widely held belief that NPC1L1

  6. PTHrP regulates water absorption and aquaporin expression in the intestine of the marine sea bream (Sparus aurata, L.).

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Canário, Adelino V M; Power, Deborah M; Fuentes, Juan

    2015-03-01

    Water ingestion by drinking is fundamental for ion homeostasis in marine fish. However, the fluid ingested requires processing to allow net water absorption in the intestine. The formation of luminal carbonate aggregates impacts on calcium homeostasis and requires epithelial HCO3(-) secretion to enable water absorption. In light of its endocrine importance in calcium handling and the indication of involvement in HCO3(-) secretion the present study was designed to expose the role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion, water absorption and the regulation of aqp1 gene expression in the anterior intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34) was added to anterior intestine of the sea bream mounted in Ussing chambers. The effect achieved a maximum inhibition of 60% of basal secretion rates, showing a threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) or the phospholipase C inhibitor (U73122, 10 μmol l(-1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in both cases. In parallel, bulk water absorption measured in intestinal sacs was sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect of 60-65% inhibition from basal rates and shows threshold significant effects at hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was completely abolished in the presence of the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 μmol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP acts as a key

  7. Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

    PubMed Central

    Cho, Hyun-Jong; Park, Jin Woo; Yoon, In-Soo; Kim, Dae-Duk

    2014-01-01

    Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel. PMID:24531717

  8. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells.

  9. The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity

    PubMed Central

    Tang, Lieqi; Cheng, Catherine Y.; Sun, Xiangrong; Pedicone, Alexandra J.; Mohamadzadeh, Mansour; Cheng, Sam X.

    2016-01-01

    Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be

  10. Absorption of iron from ferritin is independent of heme iron and ferrous salts in women and rat intestinal segments.

    PubMed

    Theil, Elizabeth C; Chen, Huijun; Miranda, Constanza; Janser, Heinz; Elsenhans, Bernd; Núñez, Marco T; Pizarro, Fernando; Schümann, Klaus

    2012-03-01

    Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC (59)Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without non-ferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained >90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency.

  11. Gastric emptying, intestinal absorption of electrolytes and exercise performance in electrolyte-supplemented horses.

    PubMed

    Lindinger, Michael I; Ecker, Gayle L

    2013-01-01

    Horses lose considerably more electrolytes through sweating during prolonged exercise than can be readily replaced through feeds. The present study tested an oral electrolyte supplement (ES) designed to replace sweat electrolyte losses. We measured gastric emptying of 3 litres of ES (using gamma imaging of (99)Tc-sulfide colloid), the absorption of Na(+) and K(+) from the gastrointestinal tract using (24)Na(+) and (42)K(+), and the distribution of these ions in the body by measuring radioactivity within plasma and sweat during exercise. Three litres of ES emptied from the stomach as fast as water, with a half-time of 47 min, and appeared in plasma by 10 min after administration (n = 4 horses). Peak values of plasma (24)Na(+) and (42)K(+) radioactivity occurred at 20-40 min, and a more rapid disappearance of K(+) radioactivity from plasma was indicative of movement of K(+) into cells (n = 3 horses). In a randomized crossover experiment (n = 4 horses), 1 h after administration of placebo (water), 1 or 3 litres of ES containing (24)Na(+), horses exercised on a treadmill at 30% of peak oxygen uptake until voluntary fatigue. The (24)Na(+) appeared in sweat at 10 min of exercise, and when horses received 3 litres of ES the duration to voluntary fatigue was increased in all horses by 33 ± 10%. It is concluded that an oral ES designed to replace sweat ion losses was rapidly emptied from the gastrointestinal tract, rapidly absorbed in the upper intestinal tract and rapidly distributed within the body. The ES clearly served as a reservoir to replace sweat ion losses during exercise, and administration of ES prior to exercise resulted in increased duration of submaximal exercise.

  12. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    PubMed

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+),K(+)-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  13. Soybean β-Conglycinin Induces Inflammation and Oxidation and Causes Dysfunction of Intestinal Digestion and Absorption in Fish

    PubMed Central

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    β-conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na+,K+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects. PMID:23520488

  14. Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans.

    PubMed

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2014-11-01

    Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As a novel in vitro system for the evaluation of drug absorption, we characterized a human small intestinal epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation from ISCs consistently conferred the capability of maturation of enterocytes to HIECs over 25 passages. The morphologically matured HIEC monolayer consisted of polarized columnar epithelia with dense microvilli, tight junctions, and desmosomes 8 days after seeding onto culture inserts. Transepithelial electrical resistance across the monolayer was 9-fold lower in HIECs (98.9 Ω × cm(2)) than in Caco-2 cells (900 Ω × cm(2)), which indicated that the looseness of the tight junctions in the HIEC monolayer was similar to that in the human small intestine (approximately 40 Ω × cm(2)). No significant differences were observed in the overall gene expression patterns of the major drug-metabolizing enzymes and transporters between the HIEC and Caco-2 cell monolayers. Furthermore, the functions of P-glycoprotein and breast cancer resistance protein in the HIEC monolayer were confirmed by the vectorial transport of marker substrates and their disappearance in the presence of specific inhibitors. The apparent drug permeability values of paracellularly transported compounds (fluorescein isothiocyanate-dextran 4000, atenolol, and terbutaline) and nucleoside transporter substrates (didanosine, ribavirin, and doxifluridine) in the HIEC monolayer were markedly higher than those of Caco-2 cells, whereas transcellularly transported drugs (pindolol and midazolam) were equally well permeated. In conclusion, the HIEC monolayer can serve as a novel and superior alternative to the conventional Caco-2 cell monolayer for predicting oral absorption in humans.

  15. The rule of unity for human intestinal absorption 2: application to pharmaceutical drugs that are marketed as salts.

    PubMed

    Patel, Raj B; Admire, Brittany; Yalkowsky, Samuel H

    2015-01-01

    The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA <0.5) and those that are well absorbed (FA ≥ 0.5). Inspection of the data as well as a receiver operative characteristic (ROC) plot shows that a single critical MAP value can be used for predicting efficient human absorption of drugs. This forms the basis of a simple rule of unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

  16. Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption.

    PubMed

    Moran, A W; Al-Rammahi, M; Zhang, C; Bravo, D; Calsamiglia, S; Shirazi-Beechey, S P

    2014-01-01

    Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep

  17. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S; Feng, Jingjing; Joshi, Sneha S

    2010-07-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.

  18. An evaluation of in vitro intestinal absorption of iron, calcium and potassium in chickens receiving gold nanoparticles.

    PubMed

    Sembratowicz, I; Ognik, K; Stępniowska, A

    2016-08-01

    This study evaluated the effect of oral administration of colloidal gold nanoparticles on accumulation of gold in the small intestine and intestinal absorption of iron, calcium and potassium under in vitro conditions. The gold nanoparticles are non-ionic, nanocrystalline, chemically pure particles 5 nm in size, produced in a physical process. In total, 126 one day-old Ross 308 chicks were assigned to 7 experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive gold nanoparticles. Groups: Au-5(7), Au-10(7) and Au-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg l(-1) for group Au-5(7), 10 mg l(-1) for group Au-10(7) and 15 mg l(-1) for group Au-15(7) in 8-14, 22-28 and 36-42 d of life. The birds in groups Au-5(3), Au-10(3) and Au-15(3) received gold nanoparticles in the same amounts, but only in 8-10, 22-24 and 36-38 d of life. The study revealed that nanogold supplied via ingestion leads to dose- and time-dependent accumulation of gold in the intestinal walls. Nanogold present in the jejunum has a negative impact on the absorption of calcium, iron and potassium under in vitro conditions.

  19. Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption.

    PubMed

    Ghosal, Abhisek; Lambrecht, Nils; Subramanya, Sandeep B; Kapadia, Rubina; Said, Hamid M

    2013-01-01

    The Slc5a6 gene expresses a plasma membrane protein involved in the transport of the water-soluble vitamin biotin; the transporter is commonly referred to as the sodium-dependent multivitamin transporter (SMVT) because it also transports pantothenic acid and lipoic acid. The relative contribution of the SMVT system toward carrier-mediated biotin uptake in the native intestine in vivo has not been established. We used a Cre/lox technology to generate an intestine-specific (conditional) SMVT knockout (KO) mouse model to address this issue. The KO mice exhibited absence of expression of SMVT in the intestine compared with sex-matched littermates as well as the expected normal SMVT expression in other tissues. About two-thirds of the KO mice died prematurely between the age of 6 and 10 wk. Growth retardation, decreased bone density, decreased bone length, and decreased biotin status were observed in the KO mice. Microscopic analysis showed histological abnormalities in the small bowel (shortened villi, dysplasia) and cecum (chronic active inflammation, dysplasia) of the KO mice. In vivo (and in vitro) transport studies showed complete inhibition in carrier-mediated biotin uptake in the intestine of the KO mice compared with their control littermates. These studies provide the first in vivo confirmation in native intestine that SMVT is solely responsible for intestinal biotin uptake. These studies also provide evidence for a casual association between SMVT function and normal intestinal health.

  20. In vitro-in vivo correlation of the effect of supersaturation on the intestinal absorption of BCS Class 2 drugs.

    PubMed

    Higashino, Haruki; Hasegawa, Tsubasa; Yamamoto, Mari; Matsui, Rie; Masaoka, Yoshie; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji

    2014-03-03

    The aim of this study was to establish an in vitro method for evaluating the effect of supersaturation on oral absorption of poorly water-soluble drugs in vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model drugs. Supersaturation of each drug was induced by diluting its stock solution by fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then dissolution and precipitation profile of the drug was observed in vitro. The crystalline form of the precipitate was checked by differential scanning calorimetry (DSC). For comparison, control suspension was prepared by suspending a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal absorption of the drug was observed in rats by determined the plasma concentration after intraduodenal administration of drug suspensions. For all drugs, suspensions prepared by solvent-shift method showed significantly higher dissolved concentration in vitro than that prepared by powder-suspending method, clearly indicated the induction of supersaturation. DSC analysis revealed that crystalline form of the precipitate profoundly affects the extent and the duration of supersaturation. A rat in vivo study confirmed that the supersaturation of these drugs increased the fraction absorbed from the intestine, which corresponded well to the in vitro dissolution and precipitation profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption study was performed in rats pretreated with 1-aminobenzotriazole, a potent inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the high luminal concentration of ketoconazole caused by supersaturation saturated the metabolic enzymes and further increased the systemic exposure of the absorbed drug. The additional effects of supersaturation on the absorption of ketoconazole are consistent with previous studies in humans under differing gastric pH conditions. In conclusion, effects of supersaturation on

  1. Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

    PubMed Central

    Tsukamoto, Ikuko; Hossain, Akram; Yamaguchi, Fuminori; Hirata, Yuko; Dong, Youyi; Kamitori, Kazuyo; Sui, Li; Nonaka, Machiko; Ueno, Masaki; Nishimoto, Kazuyuki; Suda, Hirofumi; Morimoto, Kenji; Shimonishi, Tsuyoshi; Saito, Madoka; Song, Tao; Konishi, Ryoji; Tokuda, Masaaki

    2014-01-01

    Background The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 μg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal

  2. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect.

    PubMed

    Koo, Sung I; Noh, Sang K

    2007-03-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases [e.g., coronary heart disease (CHD)]. The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly (-)-epigallocatechin gallate, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents.

  3. Green Tea as Inhibitor of the Intestinal Absorption of Lipids: Potential Mechanism for its Lipid-Lowering Effect1

    PubMed Central

    Koo, Sung I.; Noh, Sang K.

    2007-01-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases (CHD). The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly EGCG, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents. PMID:17296491

  4. Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

    PubMed

    Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-12-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.

  5. Study on the release of fenofibrate nanosuspension in vitro and its correlation with in situ intestinal and in vivo absorption kinetics in rats.

    PubMed

    Xu, Yuanlong; Wang, Yonglu; Li, Xue Ming; Huang, Qinqin; Chen, Wei; Liu, Ran; Chen, BaoAn; Wei, Ping

    2014-07-01

    As an oral delivery carrier for poorly water soluble drugs, the nanosuspension was prepared by melt emulsification method combined with high-pressure homogenization. The objective of this study was to clarify the absorption mechanism in rats of fenofibrate nanosuspension using the model of in situ gut perfusion. The release rate of drug from nanosuspension was fast which about 70% of the drug would be released within 5 minutes. The absorption of fenofibrate nanosuspension in the gastrointestinal (GI) tract was studied by the in situ closed loop method in rats. It was found that the absorption process in intestine was first-process with passive diffusion mechanism, and the whole intestine was the major segment for the drug absorption. Additionally, GI absorption in situ studies indicated that the fenofibrate nanosuspension had great success in regard to enhancement of intestinal absorption compared to the fenofibrate suspension of coarse powder. The pharmacokinetic characteristics were studied in rats after oral administration of fenofibrate nanosuspension or suspension at the dosage of 27 mg/kg. The plasma concentration-time curve was fitted to the one-compartment model. The correlation between in vitro dissolution (P), in situ intestinal absorption (F) and in vivo absorption (Fa) in rats was investigated with the results as follows: Fa = 6.2061P-456.38(r = 0.9559), F = 3.6911P-2.2169(r = 0.970), F = 0.5095P + 44.189(r = 0.9609). The highest level A could be obtained from the in vitro--in vivo correlation (IVIVC) between dissolution percentage and intestinal absorption of the fenofibrate nanosuspension in rats. Consequently, the in situ intestinal perfusion model could be used to predict the in vivo pharmacokinetic characteristics in rats.

  6. Modulation of NaCl absorption by [HCO(3)(-)] in the marine teleost intestine is mediated by soluble adenylyl cyclase.

    PubMed

    Tresguerres, Martin; Levin, Lonny R; Buck, Jochen; Grosell, Martin

    2010-07-01

    Intestinal HCO(3)(-) secretion and NaCl absorption are essential for counteracting dehydration in marine teleost fish. We investigated how these two processes are coordinated in toadfish. HCO(3)(-) stimulated a luminal positive short-circuit current (I(sc)) in intestine mounted in Ussing chamber, bathed with the same saline solution on the external and internal sides of the epithelium. The I(sc) increased proportionally to the [HCO(3)(-)] in the bath up to 80 mM NaHCO(3), and it did not occur when NaHCO(3) was replaced with Na(+)-gluconate or with NaHCO(3) in Cl(-)-free saline. HCO(3)(-) (20 mM) induced a approximately 2.5-fold stimulation of I(sc), and this [HCO(3)(-)] was used in all subsequent experiments. The HCO(3)(-)-stimulated I(sc) was prevented or abolished by apical application of 10 muM bumetanide (a specific inhibitor of NKCC) and by 30 microM 4-catechol estrogen [CE; an inhibitor of soluble adenylyl cyclase (sAC)]. The inhibitory effects of bumetanide and CE were not additive. The HCO(3)(-)-stimulated I(sc) was prevented by apical bafilomycin (1 microM) and etoxolamide (1 mM), indicating involvement of V-H(+)-ATPase and carbonic anhydrases, respectively. Immunohistochemistry and Western blot analysis confirmed the presence of an NKCC2-like protein in the apical membrane and subapical area of epithelial intestinal cells, of Na(+)/K(+)-ATPase in basolateral membranes, and of an sAC-like protein in the cytoplasm. We propose that sAC regulates NKCC activity in response to luminal HCO(3)(-), and that V-H(+)-ATPase and intracellular carbonic anhydrase are essential for transducing luminal HCO(3)(-) into the cell by CO(2)/HCO(3)(-) hydration/dehydration. This mechanism putatively coordinates HCO(3)(-) secretion with NaCl and water absorption in toadfish intestine.

  7. CTG-loaded liposomes as an approach for improving the intestinal absorption of asiaticoside in Centella Total Glucosides.

    PubMed

    Wang, Jiayu; Ma, Changhua; Guo, Chengjie; Yuan, Ruijuan; Zhan, Xueyan

    2016-07-25

    Centella Total Glucosides (CTG),obtained from Centella asiatica (L.), have been shown to possess a multitude of pharmacological activities, however, oral administeration of CTG failed to fulfill their therapeutic potentials due to the low bioavailability. In this study, the author prepared the liposomes encapsulated CTG using the ethanol injection method in order to enhance their intestinal absorption. The average particle size and the polydispersityindex(PDI) of CTG-loaded liposome in a batch are 137.0nm and 0.283, and the CTG-loaded amounts in CTG-loaded liposomes were 0.177mgmL(-1) and the zeta potential of CTG-loaded lipsomes is -21.2mV. The TEM images of CTG-loaded lipsomes showed that CTG-loaded liposomes are round and maintain high structural integrity, and their DSC thermograms indicated that CTG might be incorporated into the aqueous phase of DPPC to become more stable. The everted rat gut sac model was used to study the absorption characteristic of CTG-loaded solution in rat intestines. The cumulative absorption amount (Q) and the cumulative absorption percentage (P%) of asiaticoside in the CTG-loaded liposome was significantly higher than that in CTG (P<0.05), both the steady-state infiltration rate (Jss, μgcm(-2)s(-1)) and the permeability coefficient (Papp, cms(-1)) of asiaticoside in CTG-loaded liposomes were significantly higher than those in CTG (P<0.05), which revealed that the liposomes encapsulated CTG can promote the absorption of asiaticoside in the ileum of the rats by enhancing its transmembrane permeability. The above study will provide the experimental evidence and a reference for the development of the oral dosage forms of Centella total glucosides.

  8. Availability to rats of iron from spinach: Effects of oxalic acid.

    PubMed

    Van Campen, D R; Welch, R M

    1980-08-01

    The availability to rats of iron from two varieties of spinach was determined. Also, the absorption of Fe was compared between FeCl3 and Fe-oxalate and the effects of adding 0.75% oxalate to the diet were determined. Absorption of iron from both varieties of spinach was comparable to that from FeCl3 and the iron was equally available from Fe-oxalate and FeCl3. The addition of 0.75% oxalic acid to the diet did not depress iron absorption and, if anything, appeared to enhance iron utilization by rats.

  9. A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption.

    PubMed

    Augustijns, Patrick; Wuyts, Benjamin; Hens, Bart; Annaert, Pieter; Butler, James; Brouwers, Joachim

    2014-06-16

    The purpose of this paper is to collate all recently published solubility data of orally administered drugs in human intestinal fluids (HIF) that were aspirated from the upper small intestine (duodenum and jejunum). The data set comprises in total 102 solubility values in fasted state HIF and 37 solubility values in fed state HIF, covering 59 different drugs. Despite differences in the protocol for HIF sampling and subsequent handling, this summary of HIF solubilities provides a critical reference data set to judge the value of simulated media for intestinal solubility estimation. In this regard, the review includes correlations between the reported solubilizing capacity of HIF and fasted or fed state simulated intestinal fluid (FaSSIF/FeSSIF). Correlating with HIF solubilities enables the optimal use of solubility measurements in simulated biorelevant media to obtain accurate estimates of intestinal solubility during drug development. Considering the fraction of poorly soluble new molecular entities in contemporary drug discovery, adequate prediction of intestinal solubility is critical for efficient lead optimization, early candidate profiling, and further development.

  10. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.

    PubMed

    Miyata, Masaaki; Hayashi, Kenjiro; Yamakawa, Hiroki; Yamazoe, Yasushi; Yoshinari, Kouichi

    2015-01-01

    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  11. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    PubMed Central

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONS Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  12. Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations

    SciTech Connect

    Hirayama, H.; Xu, X.; Pang, K.S. )

    1989-08-01

    Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid ({sup 14}C)glucose absorption against a concentration gradient and a lack of ({sup 3}H)-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.

  13. Weaning induces both transient and long-lasting modifications of absorptive, secretory, and barrier properties of piglet intestine.

    PubMed

    Boudry, Gaëlle; Péron, Vincent; Le Huërou-Luron, Isabelle; Lallès, Jean Paul; Sève, Bernard

    2004-09-01

    This study investigated intestinal physiology of piglets at weaning. Piglets (n = 60) weaned at 21 d were food deprived for 2 d and then tube-fed using 2 different diets (a conventional diet vs. a wheat-enriched diet). They were slaughtered at d 0, 2, 5, 8, or 15 postweaning. Jejunum, ileum, and colon were mounted in Ussing chambers. In addition, segments of the proximal jejunum of 4 growing pigs were studied 35 d after weaning. Secretory function was assessed by basal short-circuit current (Isc) and secretagogue-stimulated Isc. Glucose absorption was measured by the increase in Isc after the addition of glucose. Epithelial barrier function was measured by transmucosal resistance (R) and horseradish peroxidase (HRP) fluxes across the epithelium. There were no significant differences between the pigs fed the 2 diets for any of the parameters studied. As already reported, a transient villous atrophy was observed. At the same time, we observed an increased basal Isc in jejunum and colon, increased glucose absorption and a dramatic drop of R in jejunum. These parameters had returned to preweaning values by d 5. Weaning was also followed by long-lasting modifications. In jejunum, responses to the secretagogues and glucose absorption were decreased at wk 2 after weaning and were not different between d 15 and 35. Ileal transmucosal resistance increased on d 5 and was stable thereafter. HRP flux in jejunum declined on d 2 and stayed at this low level throughout the experiment. We conclude that weaning induces transient dramatic changes in intestinal physiology but is also a period of maturation of the intestine.

  14. Redistribution of cathepsin B activity from the endosomal-lysosomal pathway in chick intestine within 3 min of calcium absorption.

    PubMed

    Nemere, I; Norman, A W

    1991-06-01

    Earlier work has suggested that calcium-containing lysosomes are involved in 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated intestinal absorption of the divalent cation. In the present report immunofluorescent labelling studies on fixed frozen sections of chick intestine were undertaken to determine whether lysosomes could respond to calcium transport conditions in less than 5 min. Tissue prepared from vitamin D-deficient chicks dosed with vehicle or 1.3 nmol of 1,25(OH)2D3 15 h prior to use was immunofluorescently labelled for cathepsin B, a lysosomal protease. In the absence of calcium absorption, punctate staining was found in the region below the terminal web, and more diffusely in the cytoplasm. The intensity of staining was noticeably greater in sections from 1,25(OH)2D3-treated than control chicks. In sections prepared after 3 min of calcium absorption, cathepsin B staining was localized near the basal and lateral membranes of the epithelial cells. After 30 min of transport, the protease was found in the villus core regardless of vitamin D status; however, immunoreactivity within the epithelial cells of 1,25(OH)2D3-treated chick intestine had returned to pretransport intensity, whereas that of controls had not. To further investigate the specificity of the cathepsin B antibody, the intracellular compartmentalization of the protease was determined by biochemical methods. Using dosing procedures and calcium transport times equivalent to those for the immunofluorescent studies mucosae were collected by scraping, homogenized, and subcellular fractions prepared by a combination of differential and Percoll gradient centrifugation. In the absence of calcium transport, cathepsin B-specific activity was enhanced in whole homogenates, endocytic vesicles, and a lysosomal fraction prepared from intestinal epithelium of 1,25(OH)2D3-treated chicks, relative to vitamin D-deficient controls. After 3 min of calcium absorption, a profound (approximately 4-fold) decrease in

  15. Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption.

    PubMed

    Subramanian, Veedamali S; Lambrecht, Nils; Lytle, Christian; Said, Hamid M

    2016-02-15

    Riboflavin (RF) is indispensable for normal cell metabolism, proliferation, and growth. The RFVT-3 protein (product of the Slc52a3 gene) is expressed in the gut with the expression being restricted to the apical membrane domain of the polarized intestinal epithelial cells. The relative contribution of RFVT-3 to total carrier-mediated RF uptake in the native intestine, however, is not clear. We addressed this issue in the current investigation using a conditional (intestinal-specific) RFVT-3 knockout (cKO) mouse model developed by the Cre/Lox approach. All RFVT-3 cKO mice were found to be RF deficient and showed a significant growth and development retardation; also, nearly two-thirds of them died prematurely between the age of 6 and 12 wk. In vivo (intestinal and colonic loops) and in vitro (native isolated intestinal epithelial cells) uptake studies showed a severe inhibition in carrier-mediated RF uptake in the cKO mice compared with control littermates. We also observed a significant increase in the level of expression of oxidative stress-responsive genes in the intestine of the cKO mice compared with control littermates. Supplementation of the RFVT-3 cKO mice with pharmacological doses of RF led to a complete correction of the growth retardation and to normalization in the level of expression of the oxidative stress-responsive genes in the gut. These results show, for the first time, that the RFVT-3 system is the main transporter involved in carrier-mediated RF uptake in the native mouse small and large intestine, and that its dysfunction impairs normal RF body homeostasis.

  16. Absorption characteristic of paeoniflorin-6'-O-benzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats.

    PubMed

    Yang, Xiao-Dan; Wang, Chun; Zhou, Peng; Yu, Jun; Asenso, James; Ma, Yong; Wei, Wei

    2016-09-01

    1. Paeoniflorin-6'-O-benzene sulfonate (CP-25) was synthesized to improve the poor oral absorption of paeoniflorin (Pae). 2. This study was performed to investigate the absorptive behavior and mechanism of CP-25 in in situ single-pass intestinal perfusion in rats, using Pae as a control. 3. The results showed that intestinal absorption of CP-25 was neither segmental nor sex dependent. However, the main segment of intestine that absorbed Pae was the duodenum. Furthermore, passive transport was confirmed to be the main absorption pattern of CP-25. More importantly, the absorption of CP-25 was much higher than Pae in the small intestine. 4. Among the ABC transporter inhibitors, the absorption rate of Pae increased in the presence of P-gp inhibitors verapamil and GF120918, which indicated that Pae was a substrate of P-glycoprotein (P-gp), however, such was not observed in the presence of breast cancer resistance protein and multidrug resistance-associated protein 2. Finally, the ABC transporter inhibitors did not have any significant impact on CP-25 as demonstrated in the parallel studies. 5. CP-25 could improve the poor absorption of Pae, which may be attributed to both the lipid solubility enhancement and its resistance to P-gp-mediated efflux.

  17. Intestinal first-pass metabolism by cytochrome p450 and not p-glycoprotein is the major barrier to amprenavir absorption.

    PubMed

    Dufek, Matthew B; Bridges, Arlene S; Thakker, Dhiren R

    2013-09-01

    Recent studies showed that P-glycoprotein (P-gp) increases the portal bioavailability (FG) of loperamide by sparing its intestinal first-pass metabolism. Loperamide is a drug whose oral absorption is strongly attenuated by intestinal P-gp-mediated efflux and first-pass metabolism by cytochrome P450 3A (CYP3A). Here the effect of the interplay of P-gp and Cyp3a in modulating intestinal first-pass metabolism and absorption was investigated for another Cyp3a/P-gp dual substrate amprenavir, which is less efficiently effluxed by P-gp than loperamide. After oral administration of amprenavir, the portal concentrations and FG of amprenavir were approximately equal in P-gp competent and P-gp deficient mice. Mechanistic studies on the effect of P-gp on Cyp3a-mediated metabolism of amprenavir using intestinal tissue from P-gp competent and P-gp deficient mice (Ussing-type diffusion chamber) revealed that P-gp-mediated efflux caused only a slight reduction of oxidative metabolism of amprenavir. Studies in which portal concentrations and FG were measured in P-gp competent and P-gp deficient mice whose cytochrome P450 (P450) enzymes were either intact or inactivated showed that intestinal first-pass metabolism attenuates the oral absorption of amprenavir by approximately 10-fold, whereas P-gp efflux has a relatively small effect (approximately 2-fold) in attenuating the intestinal absorption. Cumulatively, these studies demonstrate that P-gp has little influence on the intestinal first-pass metabolism and FG of amprenavir and that intestinal P450-mediated metabolism plays the dominant role in attenuating the oral absorption of this drug.

  18. Efficient electron-induced removal of oxalate ions and formation of copper nanoparticles from copper(II) oxalate precursor layers

    PubMed Central

    Rückriem, Kai; Grotheer, Sarah; Vieker, Henning; Penner, Paul; Beyer, André; Gölzhäuser, Armin

    2016-01-01

    Summary Copper(II) oxalate grown on carboxy-terminated self-assembled monolayers (SAM) using a step-by-step approach was used as precursor for the electron-induced synthesis of surface-supported copper nanoparticles. The precursor material was deposited by dipping the surfaces alternately in ethanolic solutions of copper(II) acetate and oxalic acid with intermediate thorough rinsing steps. The deposition of copper(II) oxalate and the efficient electron-induced removal of the oxalate ions was monitored by reflection absorption infrared spectroscopy (RAIRS). Helium ion microscopy (HIM) reveals the formation of spherical nanoparticles with well-defined size and X-ray photoelectron spectroscopy (XPS) confirms their metallic nature. Continued irradiation after depletion of oxalate does not lead to further particle growth giving evidence that nanoparticle formation is primarily controlled by the available amount of precursor. PMID:27547602

  19. The Ingestion of Proteins and Colloidal Materials by Columnar Absorptive Cells of the Small Intestine in Suckling Rats and Mice

    PubMed Central

    Clark, Sam L.

    1959-01-01

    Proteins and colloidal materials, administered orally to suckling rats and mice, were ingested by columnar absorptive cells of the jejunum and ileum, but not of the duodenum. Bovine gamma globulin and ovalbumin were identified in the apical cytoplasm by staining with fluorescent antibody; trypan blue, Evans blue, saccharated iron oxide, and colloidal gold were detected intracellularly by their color, specific staining, and appearance in the electron microscope. Each substance was segregated in membrane-enclosed vacuoles, apparently part of a system of potentially interconnecting vacuoles and tubules in the apical cytoplasm which is continuous in places with the apical cell membrane. We postulate that ingestion of foreign materials was accomplished by pinocytosis, that is, by invagination of the apical cell membrane to form vacuoles containing material from the intestinal lumen. Approximately 18 days after birth columnar absorptive cells lost the ability to ingest proteins and colloids, and no longer contained large vacuoles and numerous tubules. At this age rats and mice lose the ability to absorb antibodies from the intestine in an immunologically intact form, and we conclude that cellular ingestion is part of the mechanism of absorption of intact proteins in suckling animals. Particulate fat apparently is absorbed in both newborn and adult animals by micropinocytosis. Thus adult animals may not have lost the capacity for pinocytosis, but rather have become selective as to what substances provoke it. Cortisone acetate, administered subcutaneously to rats 8 to 10 days old alters the columnar absorptive cells within 72 hours so that they resemble the cells in adult animals and no longer ingest proteins. PMID:13630932

  20. The influence of lactose intolerance and other gastro-intestinal tract disorders on L-thyroxine absorption.

    PubMed

    Ruchała, Marek; Szczepanek-Parulska, Ewelina; Zybek, Ariadna

    2012-01-01

    The preferred treatment for hypothyroidism is oral levothyroxine (LT4) ingestion, in doses that ensure a sustained state of hormonal balance. Many different factors may significantly influence the absorption of LT4, including: interval between the ingestion of the drug and the last meal, eating habits, and different functional and organic pathologies of the gastro-intestinal tract. The main purpose of this paper is to review and systematise the available literature on the subject of the influence of different malabsorption syndromes on the effectiveness of LT4 preparations. The need to use high LT4 doses in the substitutional treatment of hypothyroidism is often the very first sign of one of the pathologies that are connected with malabsorption syndrome, which might have been asymptomatic and undiagnosed previously. Patients who require more than 2 μg/kg body weight of LT4 per day, with constantly increased thyrotropin level, should be diagnosed with the suspicion of pseudomalabsorption or real absorption disorder. An LT4 absorption test, using high doses of LT4, may be useful in the diagnosis of pseudomalabsorption. After excluding non-compliance, the differential diagnosis should include such disorders as lactose intolerance, coeliac disease, atrophic gastritis, Helicobacter pylori infection, bowel resection, inflammatory bowel disease, and parasite infection. Where there is a diagnosis of lactose intolerance, both a low lactose diet and a lactose-free LT4 preparation should be administered to restore euthyroidism or make it possible to decrease the dose of the LT4 preparation. In coeliac disease, a gluten-free diet usually allows a normalisation of the need for LT4, as do eradication of the H. pylori infection or parasite colonisation. In cases of atrophic gastritis or inflammatory bowel disease, treating the underlying diseases and regaining the state of remission may improve the absorption of LT4. In patients after gastro-intestinal tract surgery, a dose of

  1. Rapid conversion of the ester prodrug abiraterone acetate results in intestinal supersaturation and enhanced absorption of abiraterone: in vitro, rat in situ and human in vivo studies.

    PubMed

    Stappaerts, Jef; Geboers, Sophie; Snoeys, Jan; Brouwers, Joachim; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2015-02-01

    The aim of this study was to evaluate the intestinal disposition of abiraterone acetate, an ester prodrug of the anticancer agent abiraterone. Stability of the prodrug and solubility and dissolution characteristics of both abiraterone and abiraterone acetate were monitored in vitro. Moreover, the in vivo intraluminal concentrations of abiraterone and abiraterone acetate upon intake of one tablet of 250 mg abiraterone acetate were assessed in healthy volunteers. The intestinal absorption resulting from the intraluminal behavior of the ester prodrug was determined using the rat in situ intestinal perfusion technique with mesenteric blood sampling. Simulated and aspirated human intestinal fluids of the fasted state were used as solvent systems. Upon incubation of abiraterone acetate in human intestinal fluids in vitro, rapid hydrolysis of the prodrug was observed, generating abiraterone concentrations largely exceeding the apparent solubility of abiraterone, suggesting the existence of intestinal supersaturation. These findings were confirmed in vivo, by intraluminal sampling of duodenal fluids upon oral intake of an abiraterone acetate tablet by healthy volunteers. Rat in situ intestinal perfusion experiments performed with suspensions of abiraterone and abiraterone acetate in human intestinal fluids of the fasted state revealed significantly higher flux values upon perfusion with the prodrug than with abiraterone. Moreover, rat in situ intestinal perfusion with abiraterone acetate suspensions in simulated fluids of the fasted state in presence or absence of esterases demonstrated that increased hydrolytic activity of the perfusion medium was beneficial to the intestinal absorption of abiraterone. In conclusion, the rapid hydrolysis of abiraterone acetate in the intraluminal environment appears to result in fast and extensive generation of abiraterone supersaturation, creating a strong driving force for abiraterone absorption.

  2. LC-MS/MS determination and interaction of the main components from the traditional Chinese drug pair Danshen-Sanqi based on rat intestinal absorption.

    PubMed

    Huang, Juan; Zhang, Jing; Bai, Junqi; Xu, Wen; Wu, Dinghong; Qiu, Xiaohui

    2016-12-01

    The Chinese drug pair Danshen (Salvia miltiorrhiza)-Sanqi (Panax ginseng) has been widely used for centuries treating various cardiovascular disorders, among which salvianlic acid B (SAB), ginsenoside Rg1 (GRg1 ), ginsenoside Rb1 (GRb1 ) and notoginsenoside R1 (NGR1 ) were identified as the major components. The present study focused on the interaction between these components based on investigating their intestinal absorption using the Ussing chamber technique. The concentrations of SAB, GRg1 , GRb1 and NGR1 in the intestinal perfusate were determined by LC-MS/MS method, followed by Q (accumulative quantity) and Papp (apparent permeability). The results showed that all these four main components displayed very low permeabilities, which implied their poor absorption in the rat intestine. The intestinal absorption level of SAB displayed regioselectivity: duodenum < jejunum < ileum. However, there was no significant difference in the absorption of GRg1 and GRb1 in the different segments. The Q and Papp values of the four main components were obviously increased in jejunum when co-administrating Danshen extract with Sanqi extract. In conclusion, compatibility of Danshen and Sanqi could remarkably improve the intestinal absorption level of the main components in the pair. To some extent, this might explain the nature of the compatibility mechanisms of composite formulae in TCMs.

  3. A new in vitro system for evaluation of passive intestinal drug absorption: establishment of a double artificial membrane permeation assay.

    PubMed

    Kataoka, Makoto; Tsuneishi, Saki; Maeda, Yukako; Masaoka, Yoshie; Sakuma, Shinji; Yamashita, Shinji

    2014-11-01

    The aim of this present study was to establish a new in vitro assay, double artificial membrane permeation assay (DAMPA), to evaluate the human intestinal permeability of drugs. A double artificial membrane with an intracellular compartment was constructed in side-by-side chambers by sandwiching a filter containing buffer solution with impregnated lipophilic filters with dodecane containing 2w/v% phosphatidylcholine. Permeation data of ionic compounds clearly indicated that not only the pH value of the apical solution but also that of the intracellular compartment affected the permeability across the double artificial membrane. DAMPA was performed with 20 compounds at physiological pH (apical; 6.5, intracellular and basal; 7.4). Paracellular and transcellular permeabilities of compounds in human epithelium were estimated based on the characteristics of the paracellular pathway using physicochemical properties of compounds with the Renkin function and the area factor i.e. the difference in the effective surface area between human epithelium and the double artificial membrane, respectively. The human intestinal permeability of each compound was predicted by the sum of estimated transcellular and paracellular permeabilities. Predicted human intestinal permeability was significantly correlated with the fraction of absorbed dose in humans, indicating that DAMPA has the potential to predict oral absorption of drugs in humans.

  4. The vitamin D analog ED-71 is a potent regulator of intestinal phosphate absorption and NaPi-IIb.

    PubMed

    Brown, Alex J; Zhang, Fanjie; Ritter, Cynthia S

    2012-11-01

    The vitamin D analog ED-71 [1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D(3)] has been approved for treatment of osteoporosis in Japan, but its effects on mineral metabolism have not been fully explored. We investigated the actions of ED-71 on phosphate (Pi) absorption and induction of the intestinal sodium/phosphate cotransporters. Oral treatment of vitamin D-deficient rats with ED-71 (20 pmol every other day for 8 d) produced a maximal 8-fold increase in duodenal Pi absorption, measured by the in situ loop method, whereas 1,25-dihyroxyvitamin D(3) [1,25(OH)(2)D(3]), at doses up to 150 pmol, had no effect. This action of ED-71 was attributable to a dramatic 24-fold induction of sodium-dependent Pi transporter type IIb (NaPi-IIb) mRNA in the duodenum; Pit-1 and Pit-2 mRNA levels were not increased. In vitamin D-replete rats, ED-71 treatment (50 pmol) at 72 and 24 h before death increased NaPi-IIb mRNA in the duodenum and jejunum, but not the ileum, whereas 1,25(OH)(2)D(3) at 1000 pmol was ineffective in all segments. Single oral doses of ED-71 increased mouse intestinal NaPi-IIb mRNA and protein between 6 and 24 h. Surprisingly, rat lung NaPi-IIb was not increased by ED-71, despite its coexpression with the vitamin D receptor in alveolar type II cells. However, ED-71 did not induce intestinal NaPi-IIb in vitamin D receptor-ablated mice. The greater potency of ED-71 than 1,25(OH)(2)D(3) on NaPi-IIb appears to be due to much higher and more prolonged levels of ED-71 in the circulation. In summary, ED-71, due to its disparate pharmacokinetics, is a much more potent inducer of intestinal Pi absorption and NaPi-IIb than 1,25(OH)(2)D(3), suggesting a role for this analog in the treatment of Pi-wasting disorders.

  5. A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism

    PubMed Central

    Li, Yuling; Duan, Zhijun; Tian, Yan; Liu, Zhen; Wang, Qiuming

    2013-01-01

    In this work, we assessed the effects of sinomenine (SN) on intestinal octreotide (OCT) absorption both in Caco-2 cell monolayers and in rats. We also investigated the molecular mechanisms of tight junction (TJ) disruption and recovery by SN-mediated changes in the claudin-1 and protein kinase C (PKC) signaling pathway. The data showed that exposure to SN resulted in a significant decrease in the expression of claudin-1, which represented TJ weakening and paracellular permeability enhancement. Then, the recovery of TJ after SN removal required an increase in claudin-1, which demonstrated the transient and reversible opening for TJ. Meanwhile, the SN-mediated translocation of PKC-α from the cytosol to the membrane was found to prove PKC activation. Finally, SN significantly improved the absolute OCT bioavailability in rats and the transport rate in Caco-2 cell monolayers. We conclude that SN has the ability to enhance intestinal OCT absorption and that these mechanisms are related at least in part to the important role of claudin-1 in SN-mediated, reversible TJ opening via PKC activation. PMID:23787475

  6. Blood Trimethylamine-N-Oxide Originates from Microbiota Mediated Breakdown of Phosphatidylcholine and Absorption from Small Intestine

    PubMed Central

    Stremmel, Wolfgang; Schmidt, Kathrin V.; Schuhmann, Vera; Kratzer, Frank; Garbade, Sven F.; Langhans, Claus-Dieter; Fricker, Gert; Okun, Jürgen G.

    2017-01-01

    Elevated serum trimethylamine-N-oxide (TMAO) was previously reported to be associated with an elevated risk for cardiovascular events. TMAO originates from the microbiota-dependent breakdown of food-derived phosphatidylcholine (PC) to trimethylamine (TMA), which is oxidized by hepatic flavin-containing monooxygenases to TMAO. Our aim was to investigate the predominant site of absorption of the bacterial PC-breakdown product TMA. A healthy human proband was exposed to 6.9 g native phosphatidylcholine, either without concomitant treatment or during application with the topical antibiotic rifaximin, or exposed only to 6.9 g of a delayed-release PC formulation. Plasma and urine concentrations of TMA and TMAO were determined by electrospray ionization tandem mass spectrometry (plasma) and gas chromatography-mass spectrometry (urine). Native PC administration without concomitant treatment resulted in peak plasma TMAO levels of 43 ± 8 μM at 12 h post-ingestion, which was reduced by concomitant rifaximin treatment to 22 ± 8 μM (p < 0.05). TMAO levels observed after delayed-release PC administration were 20 ± 3 μM (p < 0.001). Accordingly, the peak urinary concentration at 24 h post-exposure dropped from 252 ± 33 to 185 ± 31 mmol/mmol creatinine after rifaximin treatment. In contrast, delayed-release PC resulted in even more suppressed urinary TMAO levels after the initial 12-h observation period (143 ± 18 mmol/mmol creatinine) and thereafter remained within the control range (24 h: 97 ± 9 mmol/mmol creatinine, p < 0.001 24 h vs. 12 h), indicating a lack of substrate absorption in distal intestine and large bowel. Our results showed that the microbiota in the small intestine generated the PC breakdown product TMA. The resulting TMAO, as a cardiovascular risk factor, was suppressed by topical-acting antibiotics or when PC was presented in an intestinally delayed release preparation. PMID:28129384

  7. Dietary iodide controls its own absorption through post-transcriptional regulation of the intestinal Na+/I- symporter.

    PubMed

    Nicola, Juan Pablo; Reyna-Neyra, Andrea; Carrasco, Nancy; Masini-Repiso, Ana Maria

    2012-12-01

    Dietary I(-) absorption in the gastrointestinal tract is the first step in I(-) metabolism. Given that I(-) is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na(+)/I(-) symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I(-) absorption system and reported reduced intestinal NIS expression in response to an I(-)-rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I(-) itself in enterocytes. Excess I(-) reduced NIS-mediated I(-) uptake in IEC-6 cells in a dose- and time-dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I(-) regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I(-) treatment, although no transcriptional effect was observed. Interestingly, I(-) decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein-based reporter constructs revealed a significant repressive effect of the I(-)-targeting NIS mRNA 3 untranslated region. In conclusion, excess I(-) downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I(-) regulates intestinal NIS mRNA expression at the post-transcriptional level as part of an autoregulatory effect of I(-) on its own metabolism.

  8. First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net ...

  9. Adolescence: How do we increase intestinal calcium absorption to allow for bone mineral mass accumulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal...

  10. Extensive gut metabolism limits the intestinal absorption of excessive supplemental dietary glutamate loads in infant pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutamate (Glu) is a major intestinal oxidative fuel, key neurotransmitter, and may be a useful dietary supplement to augment health of the infant gut. We quantified the metabolic fate of various supplemental dietary Glu intakes in young pigs surgically implanted with vascular, intraduodenal (ID), o...

  11. In vitro study of soil arsenic release by human gut microbiota and its intestinal absorption by Caco-2 cells.

    PubMed

    Yin, Naiyi; Cai, Xiaolin; Du, Huili; Zhang, Zhennan; Li, Zejiao; Chen, Xiaochen; Sun, Guoxin; Cui, Yanshan

    2017-02-01

    Arsenic (As) speciation is essential in assessing health risks from As-contaminated soil. Release of soil-bound arsenic, As transformation by human gut microbiota, and the subsequent intestinal absorption of soil As metabolites were evaluated. A colon microbial community in a dynamic human gut model and the intestinal epithelial cell line Caco-2 were cultured. Arsenic speciation analysis and absorption of different As species were undertaken. In this study, soil As release (3.7-581.2 mg kg(-1)) was observed in the colon. Arsenic in the colon digests was transformed more quickly than that in the soil solid phase. X-ray absorption near-edge spectroscopy (XANES) analysis showed that 44.2-97.6% of arsenite [As(III)] generated due to arsenate [As(V)] reduction was in the soil solid phase after the colon phase. We observed a high degree of cellular absorption of soil As metabolites, exhibiting that the intestinal absorption of monomethylarsonic acid and As(III) (33.6% and 30.2% resp.) was slightly higher than that of dimethylarsinic acid and As(V) (25.1% and 21.7% resp.). Our findings demonstrate that human gut microbiota can directly release soil-bound arsenic, particularly As-bearing amorphous Fe/Al-oxides. Determining As transformation and intestinal absorption simultaneously will result in an accurate risk assessment of human health with soil As exposures.

  12. Contrasting effects of the stomach and small intestine of rats on copper absorption

    SciTech Connect

    Fields, M.; Craft, N.; Lewis, C.; Holbrook, J.; Rose, A.; Reiser, S.; Smith, J.C.

    1986-11-01

    Since the severity of copper deficiency has been shown to be enhanced by feeding diets containing fructose but ameliorated by diets containing starch, we decided to investigate the effect of fructose or starch on copper absorption. As copper transport has been reported to occur also from the stomach, it was possible that copper absorption is inhibited by fructose already from that tissue. Under anesthesia, stomachs of 72 rats fed copper-deficient or supplemented diets containing fructose or starch were ligated prior to the oral administration of /sup 64/Cu. Gastric absorption of /sup 64/Cu was studied when the isotope was administered by gastric tube either in diet containing fructose or starch or in water. /sup 64/Cu was not absorbed from the stomach regardless of the type of dietary treatment, copper status or whether the copper was administered either in diet or in water. In addition, the absorption of /sup 64/Cu from a diet containing either fructose or starch or from a saline solution was studied using the isolated ligated duodenal loop. When /sup 64/Cu was administered with dietary fructose /sup 64/Cu retention and absorption were impaired when compared to starch. When /sup 64/Cu was administered in saline solution, differences in retention and absorption between the four dietary groups disappeared. It is suggested that the requirements for copper rather than the decreased absorption of copper are responsible at least in part for the more pronounced severity of copper deficiency in rats fed fructose compared to those fed starch.

  13. Luminal glucose does not enhance active intestinal calcium absorption in mice: evidence against a role for Ca(v)1.3 as a mediator of calcium uptake during absorption.

    PubMed

    Reyes-Fernandez, Perla C; Fleet, James C

    2015-11-01

    Intestinal Ca absorption occurs through a 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels after a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine-week-old male C57BL/6 J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week, and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), calbindin D9k (CaBPD9k), and Cav1.3 messenger RNA (mRNA) levels were measured in the duodenum, jejunum, and ileum. TRPV6 and CaBPD9k expressions were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs, whereas Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low-Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (P = .003), serum 1,25(OH)2D3 (P < .001), and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (P = .6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo.

  14. Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

    PubMed

    Bao, Chengmei; Hu, Sen; Zhou, Guoyong; Tian, Yijun; Wu, Yan; Sheng, Zhiyong

    2010-01-01

    We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES

  15. Intestinal paracellular absorption is necessary to support the sugar oxidation cascade in nectarivorous bats.

    PubMed

    Rodriguez-Peña, Nelly; Price, Edwin R; Caviedes-Vidal, Enrique; Flores-Ortiz, Cesar M; Karasov, William H

    2016-03-01

    We made the first measurements of the capacity for paracellular nutrient absorption in intact nectarivorous bats. Leptonycteris yerbabuenae (20 g mass) were injected with or fed inert carbohydrate probes L-rhamnose and D(+)-cellobiose, which are absorbed exclusively by the paracellular route, and 3-O-methyl-D-glucose (3OMD-glucose), which is absorbed both paracellularly and transcellularly. Using a standard pharmacokinetic technique, we collected blood samples for 2 h after probe administration. As predicted, fractional absorption (f) of paracellular probes declined with increasing Mr in the order of rhamnose (f=0.71)>cellobiose (f=0.23). Absorption of 3OMD-glucose was complete (f=0.85; not different from unity). Integrating our data with those for glucose absorption and oxidation in another nectarivorous bat, we conclude that passive paracellular absorption of glucose is extensive in nectarivorous bat species, as in other bats and small birds, and necessary to support high glucose fluxes hypothesized for the sugar oxidation cascade.

  16. Enhanced small intestinal absorption of beta-lactam antibiotics in rats in the presence of monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi).

    PubMed

    Yata, N; Sugihara, N; Yamajo, R; Murakami, T; Higashi, Y; Kimata, H; Nakayama, K; Kuzuki, T; Tanaka, O

    1986-02-01

    Monodesmoside, saponin A, B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) have been shown to promote absorption of poorly absorbed beta-lactam antibiotics by the small intestine using an in situ loop method. Monodesmosides were solubilized with ginseng crude saponin extract, a mixture of bisdesmosides, saponin X, Y1 and Y2 which were isolated also from Sapindus mukurossi. These solubilizing agents were demonstrated not to influence the absorption promoting effect of monodesmosides. Among the monodesmosides, saponin B showed the greatest effect. No influence of osmolarity of the administered solution on the absorption promoting action was observed. The promoting functions of the three monodesmosides for the small intestinal absorption of antibiotics were suppressed by Ca2+ ion coexisting in the administered solution.

  17. Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

    PubMed Central

    Chen, Yan; Zhao, Yan Hong; Jia, Xiao Bin; Hu, Ming

    2008-01-01

    Purpose The purpose is to determine absorption mechanism of five bioactive prenylated flavonoids (baohuoside I, icariin, epimedine A, B, and C) present in heat-processed Epimedium koreanum Nakai (Yin Yanghuo). Methods Transport of five prenylated flavonoids present in heat-processed herbs were studied in the human intestinal Caco-2 model and the perfused rat intestinal model. Results In the perfused rat intestinal model, prenylated flavonoids with a monoglucosidic bond (e.g., icariin) was rapidly hydrolyzed into corresponding metabolites (e.g., baohuoside I). In the Caco-2 model, apical to basolateral permeability of a monoglycoside baohuoside I (1.46 ×10−6 cm/sec) was more than 2 folds greater than four prenylated flavonoids with 2 or more sugar moieties (<0.6×10−6 cm/sec). The slow apical to basolateral transport of baohuoside I was the result of efflux. This efflux was carrier-mediated and active since its transport was vectorial, concentration- and temperature-dependent with activation energies greater than 15 kcal/mol. Efflux of baohuoside I was significantly suppressed by inhibitors of BCRP and MRP2, whereas efflux of icariin was significantly inhibited only by p-glycoprotein inhibitor verapamil. Because YHH is often heat-processed for better efficacy, we determined and found the optimal condition for increasing contents of more bioavailable flavonoids (i.e., baohuoside I) to be 160–170°C for 5–7 min. Conclusions Poor bioavailability of prenylated flavonoids results from their poor intrinsic permeation and transporter-mediated efflux. Heat processing parameters may be optimized to preserve the herb’s bioavailable flavonoids, which help retain and improve its efficacy during processing. PMID:18459036

  18. Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study.

    PubMed

    Matsumoto, Mitsuharu; Ooga, Takushi; Kibe, Ryoko; Aiba, Yuji; Koga, Yasuhiro; Benno, Yoshimi

    2017-01-01

    Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood in vivo, and the present findings are critical for clarifying host-intestinal bacterial interactions.

  19. Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study

    PubMed Central

    Matsumoto, Mitsuharu; Ooga, Takushi; Kibe, Ryoko; Aiba, Yuji; Koga, Yasuhiro; Benno, Yoshimi

    2017-01-01

    Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood in vivo, and the present findings are critical for clarifying host-intestinal bacterial interactions. PMID:28121990

  20. The effect of canola meal tannins on the intestinal absorption capacity of broilers using a D-xylose test.

    PubMed

    Mansoori, B; Rogiewicz, A; Slominski, B A

    2015-12-01

    In three D-xylose absorption experiments, the effect of 1% HCl/methanol, 70% methanol or 70% acetone extracts of canola meal (CM) or 70% acetone extract of soybean meal (SBM) containing polyphenols, phenolic acids, tannins and phytic acid on intestinal absorption capacity of broilers was determined. In Exp. 1, the experimental groups received orally D-xylose solution alone or with methanol/HCl, methanol or acetone extracts of CM. In Exp. 2, the experimental groups received D-xylose alone or with acetone extracts of CM or SBM. In Exp. 3, the experimental groups received D-xylose plus sucrose solution or D-xylose plus acetone extracts of CM or SBM. In Exps. 2 and 3, the CM extracts contained 2.7 and 2.6, 2.4 and 2.3, 3.2 and 3.2, and 2.4 and 2.2 times higher polyphenols, phenolic acids, tannins and condensed tannins than the corresponding SBM extracts respectively. Blood samples were collected in 40-min intervals, and plasma D-xylose was measured. Compared to the Control, plasma D-xylose in Exp. 1 was lower (p < 0.001) by 81, 69 and 73% at 40-min, by 41, 44 and 37% at 80-min and by 22, 31, and 23% at 120-min post-ingestion of the HCl/methanol, methanol and acetone extracts respectively. In both Exps. 2 and 3, plasma D-xylose level was lower (p < 0.001) in groups dosed with CM extract or SBM extract at each time of blood collection, when compared to the respective Control group. However, in Exp. 3, birds dosed with SBM extract had higher plasma D-xylose than CM extract-dosed birds by 28, 8 and 21% at 40, 80 and 120 min respectively (p < 0.01). In conclusion, although CM extract caused a lower absorption of D-xylose, based on 5 to 10% of CM inclusion levels in practical broiler rations, the soluble bioactive components of CM will likely have minor impact on the absorption capacity of the chicken intestine.

  1. Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans.

    PubMed

    Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

    2011-06-01

    Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (-32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (-43%, PE meal vs. control; P < 0.0001) and plasma (-54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans.

  2. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat.

    PubMed

    Lehr, C M; Bouwstra, J A; Kok, W; De Boer, A G; Tukker, J J; Verhoef, J C; Breimer, D D; Junginger, H E

    1992-05-01

    The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.

  3. Inhibitory effect of aluminium on calcium absorption in small intestine of rats with different thyroid hormone status.

    PubMed

    Orihuela, Daniel

    2009-11-01

    To analyse the influence of thyroid status on the effect of aluminium (Al) upon intestinal calcium (Ca) absorption, adult male Wistar rats with experimentally altered thyroid hormones circulating levels, were orally treated (o.g.) with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight (b.w.) per day, for a 14 d period. Hyper- and hypo-thyroid conditions were respectively achieved by means of administration of either sodium levothyroxine (50 microg/kg b.w. per day, o.g.) or methimazole, a thyroxine synthesis inhibitor (1mg/kg b.w. per day, o.g.). In duodenum-jejunum segments, in vitro mucosa-to-serosa (45)Ca flux (JCa(ms)) and kinetics of (45)Ca uptake in isolated enterocytes, were determined. In serum, concentrations of thyroxine (T4) and triiodothyronine (T3) were measured by chemiluminescent enzyme immunoassay. Unlike non-Al-treated rats, JCa(ms) of Al-exposed rats decreased as serum levels of T4 and T3 increased, showing a significant inverse correlation in both cases (T4: r(2)=0.414, P=0.024; T3: r(2)=0.443, P=0.018). Enterocytes isolated from rats treated with Al plus thyroxine showed a reduction of both maximum Ca uptake (4.86+/-0.44 vs. 6.85+/-1.04 nmol Ca/mg protein, P<0.05) and K(m) (0.84+/-0.18 vs. 1.05+/-0.36 mM, P<0.05) when compared to control. The observed variability in the Al effect on Ca transport with thyroid status of rats could be reflecting a negative interaction of Al with thyroid hormone action mechanisms on intestinal Ca absorption, which would take place mainly at Ca entry into enterocyte from lumen.

  4. Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.

    PubMed

    Takatsuka, Shinya; Kitazawa, Takeo; Morita, Takahiro; Horikiri, Yuji; Yoshino, Hiroyuki

    2006-01-01

    The effect of co-administration of a mucolytic agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a mucolytic agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs.

  5. Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose

    SciTech Connect

    Donatucci, D.A.; Liener, I.E.; Gross, C.J.

    1987-12-01

    The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of /sup 125/I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of (/sup 14/C)glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of their counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans.

  6. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a >/= 6-d stool or 3-d urine collection. We evaluated alternative meth...

  7. Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro.

    PubMed

    Cornaire, G; Woodley, J F; Saivin, S; Legendre, J Y; Decourt, S; Cloarec, A; Houin, G

    2000-06-01

    Surfactants are classically used to improve the solubilization of lipophilic drugs such as digoxin. Polysorbate 80 and Cremophor EL (polyoxyl 35 castor oil) are such surfactants but they may also modulate the action of P-glycoprotein, an energy-dependent "counter-transport" system implicated in the phenomenon of multidrug resistance in cancer cells. P-glycoprotein is also present in the intestine on the apical membrane of mature enterocytes and can potentially reduce the absorption of a wide range of drugs. In this study, using the improved everted gut sac method, the effects of Polysorbate 80, Cremophor EL and cyclosporin on the absorption of digoxin were studied. An increase in the uptake of digoxin in the presence of these three products could be shown with our in vitro model. Cremophor EL and Polysorbate 80 had no toxic effects at the concentrations used. These results suggest that surfactants such as Cremophor EL and Polysorbate 80 should not only support solubilization but can also modulate the P-glycoprotein system to improve the bioavailability of poorly absorbed drugs.

  8. FETAL RAT INTESTINAL ABSORPTION OF HORSERADISH PEROXIDASE FROM SWALLOWED AMNIOTIC FLUID

    PubMed Central

    Orlic, Donald; Lev, Robert

    1973-01-01

    Horseradish peroxidase (HRP) injected into amniotic fluid is swallowed by rat fetuses and within 3–6 h reaches the gut lumen. This macromolecular protein is then absorbed by the columnar lining cells via a system of apical cytoplasmic tubules formed by invaginations of the plasma membrane. From cytoplasm subjacent to the brush border HRP is transported, within vacuoles, to the supranuclear region, where some is retained for at least 18 h, and to interepithelial spaces. Extracellular enzyme is then found throughout the epithelial basement membrane and between connective tissue cells of the mucosal and submucosal layers Finally, HRP can be detected within lumina of blood and lymphatic capillaries, strongly suggesting that it is transported from the intestine to the circulation. PMID:4118449

  9. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine

    PubMed Central

    Frank, Daniel N.; Bales, Elise S.; Monks, Jenifer; Jackman, Matthew J.; MacLean, Paul S.; Ir, Diana; Robertson, Charles E.; Orlicky, David J.; McManaman, James L.

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity. PMID:26147095

  10. Lowering urinary oxalate excretion to decrease calcium oxalate stone disease

    PubMed Central

    Knight, John; Assimos, Dean G.

    2016-01-01

    Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion. The consumption of oxalate-rich foods should be avoided and calcium intake adjusted to 1000–1200 mg/day. To encourage compliance it should be emphasized to patients that they be vigilant with this diet as a deviation in any meal or snack could potentially result in significant stone growth. The evidence underlying these two modifications is outlined and other strategies to reduce urinary oxalate excretion are reviewed. PMID:26614109

  11. Literature review for oxalate oxidation processes and plutonium oxalate solubility

    SciTech Connect

    Nash, C. A.

    2015-10-01

    A literature review of oxalate oxidation processes finds that manganese(II)-catalyzed nitric acid oxidation of oxalate in precipitate filtrate is a viable and well-documented process. The process has been operated on the large scale at Savannah River in the past, including oxidation of 20 tons of oxalic acid in F-Canyon. Research data under a variety of conditions show the process to be robust. This process is recommended for oxalate destruction in H-Canyon in the upcoming program to produce feed for the MOX facility. Prevention of plutonium oxalate precipitation in filtrate can be achieved by concentrated nitric acid/ferric nitrate sequestration of oxalate. Organic complexants do not appear practical to sequester plutonium. Testing is proposed to confirm the literature and calculation findings of this review at projected operating conditions for the upcoming campaign.

  12. Tetradecylmaltoside (TDM) enhances in vitro and in vivo intestinal absorption of enoxaparin, a low molecular weight heparin.

    PubMed

    Yang, Tianzhi; Arnold, John J; Ahsan, Fakhrul

    2005-01-01

    Tetradecylmaltoside (TDM) was evaluated as a potential gastrointestinal absorption enhancer for low molecular weight heparin (LMWH), enoxaparin. The in vitro efficacy of TDM (0.0625, 0.125 and 0.25% w/v) in enhancing transport of 3H-enoxaparin or 14C-mannitol was investigated in human colonic epithelial cells (C2BBel). Metabolic stability of the drug was determined in C2BBel cell extracts. Transepithelial electrical resistance (TEER) was measured before and after exposure of the cells to TDM. Enoxaparin was further administered to anesthetized Sprague-Dawley rats in oral formulations in the absence or presence of increasing concentrations of TDM and drug absorption was monitored by measuring anti-factor Xa activity in rat blood. In vitro permeability study shows that apparent permeability (Papp) of 3H-enoxaparin across C2BBe1 cells was increased by 8-fold in the presence of 0.0625% TDM compared to untreated cells. The movement of 14C-mannitol across the cell monolayer followed a similar pattern in the presence of increasing concentrations of TDM. No degradation or depolymerization of enoxaparin was observed when the drug was incubated in C2BBel cell extract. TEER was reversible after 60 min exposure of the cells to 0.0625% (w/v) TDM. Oral formulations of enoxaparin containing TDM administered to anesthetized rats significantly and rapidly increased gastrointestinal absorption as compared to those animals which received enoxaparin plus saline (p < 0.05). In the presence of 0.125% TDM in the formulation, enoxaparin oral bioavailability was increased by 2.5-fold compared to the saline control group. Overall, the data on the effect of TDM on the in vitro and in vivo intestinal permeation of enoxaparin suggest that TDM may represent a promising excipient for use in oral LMWH formulations.

  13. 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker.

    PubMed

    Camargo, Marília Brasilio Rodrigues; Vilaça, Tatiane; Hayashi, Lilian Fukusima; Rocha, Olguita G Ferreira; Lazaretti-Castro, Marise

    2015-05-01

    There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF) and sufficient, ≥75 nmol/L (SUF). The subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. The mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 ± 18.2 vs. 38.4 ± 8.5 nmol/L (p < 0.001) and 36.2 ± 10.2 vs. 24.9 ± 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of the test. In the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium absorption test.

  14. SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O-β-d-Glucoside in Rats.

    PubMed

    Shi, Jian; Zheng, Haihui; Yu, Jia; Zhu, Lijun; Yan, Tongmeng; Wu, Peng; Lu, Linlin; Wang, Ying; Hu, Ming; Liu, Zhongqiu

    2016-03-01

    Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-β-d-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific β-glucuronides (BSβG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 3'-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds.

  15. Effect of dietary fat on plasma glutathione peroxidase levels and intestinal absorption of /sup 75/Se-labeled sodium selenite in chicks

    SciTech Connect

    Mutanen, M.L.; Mykkaenen, H.M.

    1984-05-01

    The effect of dietary fat on the availability of selenium was investigated in chicks fed either 4 or 20% butter, olive oil, rape oil, corn oil or sunflower oil in the diet for 3 weeks after hatching. Plasma glutathione peroxidase (GSH-Px) activity was used as an indicator of the body selenium status. In addition, the intestinal absorption of sodium selenite (/sup 75/Se-labeled) was determined by using both the in vivo ligated loop procedure and oral administration of the isotope. The plasma GSH-Px levels increased with increasing proportion of the polyunsaturated fatty acids in the diet. Increasing the amount of fat from 4 to 20% significantly enhanced the GSH-Px activity in the groups receiving butter or olive oil, but had no effect in animals fed the unsaturated fats. The absorption of (/sup 75/Se)selenite from the ligated duodenal loops tended to be reduced in chicks fed corn oil or sunflower oil as compared to the animals receiving butter in their diet. On the other hand, the type of dietary fat did not appear to affect the absorption of the orally administered selenite. The present study demonstrates that the type of dietary fat can affect the plasma GSH-Px levels in chicks without altering the intestinal absorption of selenite. However, the results on the absorption of the intraduodenally injected sodium selenite suggest that dietary fat plays some role in the intestinal transport of selenium.

  16. Different Zinc Sources Have Diverse Impacts on Gene Expression of Zinc Absorption Related Transporters in Intestinal Porcine Epithelial Cells.

    PubMed

    Huang, Danping; Zhuo, Zhao; Fang, Shenglin; Yue, Min; Feng, Jie

    2016-10-01

    This study was conducted to investigate the effects of zinc sources on gene expression of zinc-related transporters in intestinal porcine epithelial cells (IPEC-1). IPEC-1 cells were treated with zinc glycine chelate (Zn-Gly), zinc methionine (Zn-Met), and zinc sulfate (ZnSO4), respectively, for measurement of cell viability. Then, the relative expression of zinc-related transporters in IPEC-1 in response to different zinc sources (50 μmol/L zinc) was measured. Zinc transporter SLC39A4 (ZIP4) expression was selectively silenced to assess the function of ZIP4 in inorganic and organic zinc absorption. The result showed that Zn-Gly and Zn-Met had lower cell damage compared with ZnSO4 on the same zinc levels. Different zinc sources improved the expression of metallothionein1 (MT1) and zinc transporter SLC30A1 (ZnT1) messenger RNA (mRNA) compared with the control (P < 0.05), while ZIP4 decreased (P < 0.05) in response to zinc addition. MT1 and ZnT1 mRNA expressions in Zn-Gly and Zn-Met were higher than those in ZnSO4, and ZIP4 mRNA expression in Zn-Met was the lowest among three kinds of zinc sources (P < 0.05). Expression of divalent metal transporter 1 (DMT1) mRNA in control was significantly higher (P < 0.05) than added different zinc sources groups. Silencing of ZIP4 significantly decreased MT1 mRNA expression in ZnSO4 and Zn-Gly treatments, reduced zinc absorption rate, and increased DMT1 mRNA expression in ZnSO4 compared with negative control. In summary, different zinc sources could improve zinc status on IPEC-1 cells and organic zinc had lower cell damage compared with ZnSO4. Moreover, Zn-Gly and Zn-Met are more efficient on zinc absorption according to the expression of various zinc-related transporters MT1, ZIP4, ZnT1, and DMT1. ZIP4 played a direct role in inorganic zinc uptake, and the absorption of zinc in Zn-Gly depends on ZIP4 partly, while absorption of Zn-Met is less dependent on ZIP4.

  17. Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification.

    PubMed

    Cvijić, Sandra; Parojčić, Jelena; Langguth, Peter

    2014-09-30

    Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.

  18. Calcium oxalate content affects the nutritional availability of calcium from Medicago truncatula leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is known that oxalate, present in edible plants, can bind calcium in a crystalline form that reduces the availability of the bound calcium for nutritional absorption by humans. It is unknown, however, the degree to which the calcium oxalate content of a plant can be genetically altered and how mu...

  19. Gut microbiota and oxalate homeostasis

    PubMed Central

    2017-01-01

    This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence. PMID:28217701

  20. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats.

    PubMed

    Sinko, P J; Balimane, P V

    1998-05-01

    The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester prodrug of acyclovir, was investigated in rats using an in situ intestinal perfusion technique. VACV demonstrates an oral bioavailability that is three to five time greater than acyclovir, concentration dependent, and saturable in humans. Homogenate and perfused buffer stability results demonstrated that VACV was increasingly unstable with increasing pH. VACV was converted to ACV in a concentration dependent manner during a single pass through the intestinal segment. Perfusions were performed at 37 degrees C, pH 6.5, and under iso-osmotic conditions (290 +/- 10 mOsm L-1). Intestinal outlet concentrations were corrected for VACV that was converted to ACV during the perfusion. The effective dimensionless intestinal permeability (P*e) of VACV was concentration dependent, saturable (intrinsic Km = 1.2 +/- 0.7 mM), and significantly reduced (p < 0.05) in the presence of peptide analogues (amoxicillin, ampicillin, cefadroxil, and cephradine), by the organic anion, p-amino hippuric acid and by the organic cation quinine. VACV transport was not inhibited by classical nucleoside competitive substrates or inhibitors or by valine. These results suggest that H(+)-oligopeptide, H(+)-organic cation, and organic anion transporters are involved in the small intestinal uptake of VACV. The permeability of VACV in the colon was very low, indicating that VACV is predominantly absorbed from the small intestine. VACV P*e was not altered in the presence of glucose-induced convective fluid flow, suggesting that carrier-mediated, transcellular uptake is the predominant absorption pathway of VACV in rat small intestine. Based on these results, the oral bioavailability of VACV appears to be significantly influenced by the preabsorptive conversion of VACV to the poorly absorbed ACV, by the involvement of multiple transporters in VACV small-intestinal uptake, and by the low permeability of VACV in the colon.

  1. Whey protein-effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression.

    PubMed

    Nilaweera, Kanishka N; Cabrera-Rubio, Raul; Speakman, John R; O' Connor, Paula M; McAuliffe, AnneMarie; Guinane, Caitriona M; Lawton, Elaine; Crispie, Fiona; Aguilera, Mònica; Stanley, Maurice; Boscaini, Serena; Joyce, Susan; Melgar, Silvia; Cryan, John F; Cotter, Paul D

    2017-03-21

    We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance related parameters were investigated. As part of a high sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2 and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated a reduced energy absorption through the intestine. We propose that this mobilised energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway.

  2. The medical management of intestinal failure: methods to reduce the severity.

    PubMed

    Nightingale, Jeremy M D

    2003-08-01

    A new definition of intestinal failure is of reduced intestinal absorption so that macronutrient and/or water and electrolyte supplements are needed to maintain health or growth. Severe intestinal failure is when parenteral nutrition and/or fluid are needed and mild intestinal failure is when oral supplements or dietary modification suffice. Treatment aims to reduce the severity of intestinal failure. In the peri-operative period avoiding the administration of excessive amounts of intravenous saline (9 g NaCl/l) may prevent a prolonged ileus. Patients with intermittent bowel obstruction may be managed with a liquid or low-residue diet. Patients with a distal bowel enterocutaneous fistula may be managed with an enteral feed absorbed by the proximal small bowel while no oral intake may be needed for a proximal bowel enterocutaneous fistula. Patients undergoing high-dose chemotherapy can usually tolerate jejunal feeding. Rotating antibiotic courses may reduce small bowel bacterial overgrowth in patients with chronic intestinal pseudoobstruction. Restricting oral hypotonic fluids, sipping a glucose-saline solution (Na concentration of 90-120 mmol/l) and taking anti-diarrhoeal or anti-secretory drugs, reduces the high output from a jejunostomy. This treatment allows most patients with a jejunostomy and > 1 m functioning jejunum remaining to manage without parenteral support. Patients with a short bowel and a colon should consume a diet high in polysaccharides, as these compounds are fermented in the colon, and low in oxalate, as 25% of the oxalate will develop as calcium oxalate renal stones. Growth factors normally produced by the colon (e.g. glucagon-like peptide-2) to induce structural jejunal adaptation have been given in high doses to patients with a jejunostomy and do marginally increase the daily energy absorption.

  3. Loss of organic anion transporting polypeptide 1a1 increases deoxycholic acid absorption in mice by increasing intestinal permeability.

    PubMed

    Zhang, Youcai; Csanaky, Iván L; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2011-12-01

    Deoxycholic acid (DCA) is a known hepatotoxicant, a tissue tumor promoter, and has been implicated in colorectal cancer. Male mice are more susceptible to DCA toxicity than female mice. Organic anion transporting polypeptide 1a1 (Oatp1a1), which is known to transport bile acids (BAs) in vitro, is predominantly expressed in livers of male mice. In addition, the concentrations of DCA and its taurine conjugate (TDCA) are increased in serum of Oatp1a1-null mice. To investigate whether Oatp1a1 contributes to the gender difference in DCA toxicity in mice, wild-type (WT) and Oatp1a1-null mice were fed a 0.3% DCA diet for 7 days. After feeding DCA, Oatp1a1-null mice had 30-fold higher concentrations of DCA in both serum and livers than WT mice. Feeding DCA caused more hepatotoxcity in Oatp1a1-null mice than WT mice. After feeding DCA, Oatp1a1-null mice expressed higher BA efflux-transporters (bile salt-export pump, organic solute transporter (Ost)α/β, and multidrug resistance-associated protein [Mrp]2) and lower BA-synthetic enzymes (cytochrome P450 [Cyp]7a1, 8b1, 27a1, and 7b1) in livers than WT mice. Intravenous administration of DCA and TDCA showed that lack of Oatp1a1 does not decrease the plasma elimination of DCA or TDCA. After feeding DCA, the concentrations of DCA in ileum and colon tissues are higher in Oatp1a1-null than in WT mice. In addition, Oatp1a1-null mice have enhanced intestinal permeability. Taken together, the current data suggest that Oatp1a1 does not mediate the hepatic uptake of DCA or TDCA, but lack of Oatp1a1 increases intestinal permeability and thus enhances the absorption of DCA in mice.

  4. Loss of Organic Anion Transporting Polypeptide 1a1 Increases Deoxycholic Acid Absorption in Mice by Increasing Intestinal Permeability

    PubMed Central

    Zhang, Youcai; Csanaky, Iván L.; Lehman-McKeeman, Lois D.; Klaassen, Curtis D.

    2011-01-01

    Deoxycholic acid (DCA) is a known hepatotoxicant, a tissue tumor promoter, and has been implicated in colorectal cancer. Male mice are more susceptible to DCA toxicity than female mice. Organic anion transporting polypeptide 1a1 (Oatp1a1), which is known to transport bile acids (BAs) in vitro, is predominantly expressed in livers of male mice. In addition, the concentrations of DCA and its taurine conjugate (TDCA) are increased in serum of Oatp1a1-null mice. To investigate whether Oatp1a1 contributes to the gender difference in DCA toxicity in mice, wild-type (WT) and Oatp1a1-null mice were fed a 0.3% DCA diet for 7 days. After feeding DCA, Oatp1a1-null mice had 30-fold higher concentrations of DCA in both serum and livers than WT mice. Feeding DCA caused more hepatotoxcity in Oatp1a1-null mice than WT mice. After feeding DCA, Oatp1a1-null mice expressed higher BA efflux-transporters (bile salt-export pump, organic solute transporter (Ost)α/β, and multidrug resistance-associated protein [Mrp]2) and lower BA-synthetic enzymes (cytochrome P450 [Cyp]7a1, 8b1, 27a1, and 7b1) in livers than WT mice. Intravenous administration of DCA and TDCA showed that lack of Oatp1a1 does not decrease the plasma elimination of DCA or TDCA. After feeding DCA, the concentrations of DCA in ileum and colon tissues are higher in Oatp1a1-null than in WT mice. In addition, Oatp1a1-null mice have enhanced intestinal permeability. Taken together, the current data suggest that Oatp1a1 does not mediate the hepatic uptake of DCA or TDCA, but lack of Oatp1a1 increases intestinal permeability and thus enhances the absorption of DCA in mice. PMID:21914718

  5. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    SciTech Connect

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  6. Oxalate Nephropathy in Systemic Sclerosis: Case Series and Review of the Literature

    PubMed Central

    Ligon, Colin B.; Hummers, Laura K.; McMahan, Zsuzsanna H.

    2015-01-01

    Objective To increase awareness of oxalate nephropathy as a cause of acute kidney injury (AKI) among systemic sclerosis patients with small intestinal dysmotility and malabsorption, and to prompt consideration of dietary modification and early treatment of predisposing causes of oxalate nephropathy in this population. Methods Two cases of biopsy-proven oxalate nephropathy were identified among systemic sclerosis patients in the course of direct clinical care. Subsequently, a retrospective search of the Johns Hopkins Pathology databases identified a third patient with systemic sclerosis who developed oxalate nephropathy. Results Among the three patients with qualifying biopsies, all three had systemic sclerosis with lower gastrointestinal involvement. All three presented with diarrhea, malabsorption, and AKI. In two of the three patients, diarrhea was present for at least two years before the development of AKI; in the third, incidental oxalate nephropathy was noted three years before she developed AKI and extensive oxalate nephropathy in the setting of a prolonged mycobacterium avium-intracellulare enteritis. In one case, oxalate crystals were present by urinalysis months before diagnosis by biopsy, in the second, hyperoxaluria was diagnosed by urine collection immediately after biopsy, and in the third, oxalate crystals had been noted incidentally on post-transplant renal biopsy three years before the development of fulminant oxalate nephropathy. All three patients died within a year of diagnosis. Conclusions Patients with systemic sclerosis and bowel dysmotility associated with chronic diarrhea and malabsorption may be at risk for an associated oxalate nephropathy. Regular screening of systemic sclerosis patients with small bowel malabsorption syndromes through routine urinalysis or 24 hour urine oxalate collection, should be considered. Further studies defining the prevalence of this complication in systemic sclerosis, the benefit of dietary modification on

  7. LITERATURE REVIEW FOR OXALATE OXIDATION PROCESSES AND PLUTONIUM OXALATE SOLUBILITY

    SciTech Connect

    Nash, C.

    2012-02-03

    A literature review of oxalate oxidation processes finds that manganese(II)-catalyzed nitric acid oxidation of oxalate in precipitate filtrate is a viable and well-documented process. The process has been operated on the large scale at Savannah River in the past, including oxidation of 20 tons of oxalic acid in F-Canyon. Research data under a variety of conditions show the process to be robust. This process is recommended for oxalate destruction in H-Canyon in the upcoming program to produce feed for the MOX facility. Prevention of plutonium oxalate precipitation in filtrate can be achieved by concentrated nitric acid/ferric nitrate sequestration of oxalate. Organic complexants do not appear practical to sequester plutonium. Testing is proposed to confirm the literature and calculation findings of this review at projected operating conditions for the upcoming campaign. H Canyon plans to commence conversion of plutonium metal to low-fired plutonium oxide in 2012 for eventual use in the Mixed Oxide Fuel (MOX) Facility. The flowsheet includes sequential operations of metal dissolution, ion exchange, elution, oxalate precipitation, filtration, and calcination. All processes beyond dissolution will occur in HB-Line. The filtration step produces an aqueous filtrate that may have as much as 4 M nitric acid and 0.15 M oxalate. The oxalate needs to be removed from the stream to prevent possible downstream precipitation of residual plutonium when the solution is processed in H Canyon. In addition, sending the oxalate to the waste tank farm is undesirable. This report addresses the processing options for destroying the oxalate in existing H Canyon equipment.

  8. Multidrug resistance proteins restrain the intestinal absorption of trans-resveratrol in rats.

    PubMed

    Juan, M Emília; González-Pons, Eulalia; Planas, Joana M

    2010-03-01

    trans-Resveratrol, a natural antioxidant, has been described as a nutraceutic compound with important beneficial effects on health, but its low oral bioavailability hinders its therapeutic activity. Here, we studied the mechanisms of apical transport of trans-resveratrol in enterocytes and the role of ATP-binding cassette (ABC) transporters in the secretion of resveratrol glucuronide and sulfate resulting from the rapid intracellular metabolism. An intestinal perfusion method with recirculation in vivo was used in rats. Jejunal loops were perfused with increasing concentrations of trans-resveratrol and results showed that its uptake occurs by simple diffusion without the participation of a mediated transport. The apparent diffusion constant was 8.1 +/- 0.3 microL/(5 min.mg dry weight). The glycoprotein-P (Pgp, ABCB1), multidrug resistance-associated protein 2 (MRP2, ABCC2), and breast cancer resistance protein (BCRP, ABCG2) located in the apical membrane of enterocytes were investigated using specific inhibitors. The Pgp inhibitors verapamil (5 micromol/L) and cyclosporin A (5 micromol/L) did not affect the efflux of trans-resveratrol and its conjugates. The MRP2 inhibitors probenecid (2 mmol/L) and MK571 (10 micromol/L) reduced the efflux of glucuronide by 61 and 55%, respectively, and of sulfate by 43 and 28%, respectively. The BCRP inhibitor Ko143 (0.5 micromol/L) decreased the secretion of glucuronide by 64% and of sulfate by 46%. Our experiments identify MRP2 and BCRP as the 2 apical transporters involved in the efflux of resveratrol conjugates.

  9. Enhanced intestinal absorption of curcumin in Caco-2 cell monolayer using mucoadhesive nanostructured lipid carriers.

    PubMed

    Chanburee, Sanipon; Tiyaboonchai, Waree

    2017-03-21

    This study aimed to compare the intestinal permeation of curcumin-loaded polymer coated nanostructured lipid carriers (NLCs) and uncoated NLCs using the Caco-2 cell model. The uncoated NLCs were prepared using a warm microemulsion technique, while polymer-coated NLCs were prepared with the same method but were followed by coating particle surface with polyethylene glycol (PEG) 400 or polyvinyl alcohol (PVA). After lyophilization, all formulations possessed a mean size of <400 nm with a zeta potential of ∼-30 mV and a high entrapment efficacy up to 90%. All NLCs formulation showed significantly improvement in curcumin water solubility, more than 60-folds as compared to curcumin dispersion. In addition, they could protect curcumin from degradation in basic pH, 90% curcumin remaining after 6 h incubation in culture medium. In vitro permeation studies revealed that PEG-NLCs and PVA-NLCs provided significantly higher apparent permeation coefficient (Papp ) value than uncoated NLCs. Moreover, after 6 months storage at 4 °C in the absence of sunlight, the physical, and chemical stabilities of the lyophilized curcumin-loaded polymer coated NLCs and uncoated NLCs could be maintained, i.e., the mean particle size and the amount of curcumin showed no significant changes (p > 0.05) compared to those freshly prepared formulations. Considered overall, polymer coated NLCs are an important strategy to improve the oral bioavailability of curcumin. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.

  10. Self-micro emulsifying formulation improved intestinal absorption and oral bioavailability of bakuchiol.

    PubMed

    Pi, Jiaxin; Gao, Xu; Yu, Yue; Zheng, Yin; Zhu, Zhuangzhi; Wang, Yajing

    2014-10-18

    Bakuchiol (BAK), isolated from the seeds of Psoralea corylifolia L., recently presents a variety of pharmacologic activities. However, the poor oral bioavailability limits its further development and clinical use. The purpose of this study was to establish a self-microemulsifying (SME) formulation for oral delivery improvement of BAK. The optimized liquid SME formulation was comprised of BAK (40 %), Cremophor RH 40 (30 %) and Labrasol (30 %). The emulsion droplets were spherical in shape, and particle size and zeta potential were determined. The in vitro dissolution test of BAK-SME formulation illustrated faster dissolution rate than the bulk drug. The permeabilities of 40 μg mL(-1) BAK-SME formulation in rat intestinal segments of duodenum, jejunum, ileum and colon were 30.91 × 10(-3), 23.61 × 10(-3), 29.43 × 10(-3) and 23.62 × 10(-3) cm min(-1), respectively, exhibiting 3.99 times in duodenum, 2.59 times in ileum and 2.31 times in colon greater than BAK perfusate. The oral bioavailability of BAK-SME formulation at a dose of 150 mg kg(-1) was determined in rats. The Cmax and the AUC(0-24h) were 515.4 ng mL(-1) and 4,327.2 h ng mL(-1), respectively, which were 1.90 fold and 1.73 fold greater than the value of BAK suspension. All these results clearly stated that BAK-SME formulation performed well-improvement on oral bioavailability of BAK.

  11. Effect of compounds affecting ABCA1 expression and CETP activity on the HDL pathway involved in intestinal absorption of lutein and zeaxanthin.

    PubMed

    Niesor, Eric J; Chaput, Evelyne; Mary, Jean-Luc; Staempfli, Andreas; Topp, Andreas; Stauffer, Andrea; Wang, Haiyan; Durrwell, Alexandre

    2014-12-01

    The antioxidant xanthophylls lutein and zeaxanthin are absorbed from the diet in a process involving lipoprotein formation. Selective mechanisms exist for their intestinal uptake and tissue-selective distribution, but these are poorly understood. We investigated the role of high-density lipoprotein (HDL), apolipoprotein (apo) A1 and ATP-binding cassette transporter (ABC) A1 in intestinal uptake of lutein in a human polarized intestinal cell culture and a hamster model. Animals received dietary lutein and zeaxanthin and either a liver X receptor (LXR) agonist or statin, which up- or down-regulate intestinal ABCA1 expression, respectively. The role of HDL was studied following treatment with the cholesteryl ester transfer protein (CETP) modulator dalcetrapib or the CETP inhibitor anacetrapib. In vitro, intestinal ABCA1 at the basolateral surface of enterocytes transferred lutein and zeaxanthin to apoA1, not to mature HDL. In hamsters, plasma lutein and zeaxanthin levels were markedly increased with the LXR agonist and decreased with simvastatin. Dalcetrapib, but not anacetrapib, increased plasma and liver lutein and zeaxanthin levels. ABCA1 expression and apoA1 acceptor activity are important initial steps in intestinal uptake and maintenance of lutein and zeaxanthin levels by an HDL-dependent pathway. Their absorption may be improved by physiological and pharmacological interventions affecting HDL metabolism.

  12. Calcium oxalate deposition in renal allografts: morphologic spectrum and clinical implications.

    PubMed

    Truong, Luan D; Yakupoglu, Ulkem; Feig, Daniel; Hicks, John; Cartwight, Joiner; Sheikh-Hamad, David; Suki, Wadi N

    2004-08-01

    Many aspects of calcium oxalate (CaOx) deposition in renal transplant biopsies are not known. Review of all renal transplant biopsies performed in a 7-year period showed that CaOx deposition could be classified into three groups. Group I: Seven biopsies within a month post-transplant displayed rare CaOx foci against a background of acute tubular necrosis or acute cell-mediated rejection. At follow-up, five grafts functioned well and two failed due to chronic allograft nephropathy. CaOx in this context was an incidental finding secondary to a sudden excretion of an end-stage renal disease-induced increased body burden of CaOx. Group II: Two biopsies performed 2 and 10 months post-transplant showed rare CaOx foci against a background of chronic allograft nephropathy, leading to graft loss. CaOx in this context reflected nonspecific parenchymal deposition due to chronic renal failure regardless of causes. Group III: One biopsy with recurrent PH1 characterized by marked CaOx deposition associated with severe tubulointerstitial injury and graft loss 6 months post-transplant. There were two previously reported cases in which CaOx deposition in the renal allografts was due the antihypertensive drug naftidrofuryl oxalate or increased intestinal absorption of CaOx. CaOx deposition in renal allografts can be classified in different categories with distinctive morphologic features and clinical implications.

  13. Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine.

    PubMed

    Wagner, Brent; Galey, William R

    2003-01-01

    Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile beta-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 microCi D-[(3)H]-mannose and 0.187 microCi D-[(14)C]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[(14)C]-glucose and D-[(3)H]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[(14)C]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants of D-[(14)C]-glucose or D-[(3)H]-mannose transport. However, treatment with 1 mM prunasin (n = 16) did reduce the influx of D-[(14)C]-glucose without affecting D-[(3)H]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1.

  14. In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

    PubMed

    López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

    2016-06-15

    Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer.

  15. Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach

    PubMed Central

    Sun, Jing; Dahan, Arik; Amidon, Gordon L.

    2011-01-01

    A prodrug strategy was applied to guanidino-containing analogs to increase oral absorption via hPEPT1 and hVACVase. L-Valine, L-isoleucine and L-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC50: 0.65 and 0.63 mM, respectively), and all three L-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG, and exceeded/matched the high-permeability standard metoprolol, respectively. All the L-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates, and were found to be good substrates of hVACVase (kcat/Km in mM−1·s−1: Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogs via targeting hPEPT1 for transport and hVACVase for activation. PMID:19957998

  16. OXALATE DEPOSITION ON ASBESTOS BODIES

    EPA Science Inventory

    The clinical and histopathologic findings in three patients with a deposition of calcium oxalate crystals on ferruginous bodies after occupational exposure to asbestos are provided. In addition, we test the hypothesis that this oxalate can be generated through a nonenzymatic o...

  17. The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium.

    PubMed

    Ognik, Katarzyna; Stępniowska, Anna; Cholewińska, Ewelina; Kozłowski, Krzysztof

    2016-09-01

    Copper nanoparticles used as a dietary supplement for poultry could affect the absorption of mineral elements. Hence the aim of the study was to determine the effect of administration of copper nanoparticles to chickens in drinking water on intestinal absorption of iron, zinc, and calcium. The experiment was carried out on 126 chicks assigned to seven experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive copper nanoparticles. Groups: Cu-5(7), Cu-10(7), and Cu-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg/L for group Cu-5(7), 10 mg/L for group Cu-10(7), and 15 mg/L for group Cu-15(7) during 8 to 14, 22 to 28, and 36 of 42 days of the life of the chicks. The birds in groups Cu-5(3), Cu-10(3), and Cu-15(3) received copper nanoparticles in the same amounts, but only during 8 to 10, 22 to 24, and 36 to 38 days of life. Blood for analysis was collected from the wing vein of all chicks at the age of 42 days. After the rearing period (day 42), six birds from each experimental group with body weight similar to the group average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. Oral administration of copper nanoparticles to chickens in the amount of 5, 10, and 15 mg/L led to accumulation of this element in the intestinal walls. The highest level of copper nanoparticles applied increased Cu content in the blood plasma of the birds. The in vitro study suggests that copper accumulated in the intestines reduces absorption of calcium and zinc, but does not affect iron absorption.

  18. Proliferation and mRNA expression of absorptive villous cell markers and mineral transporters in prolactin-exposed IEC-6 intestinal crypt cells.

    PubMed

    Teerapornpuntakit, Jarinthorn; Wongdee, Kannikar; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-06-01

    During pregnancy and lactation, prolactin (PRL) enhances intestinal absorption of calcium and other minerals for fetal development and milk production. Although an enhanced absorptive efficiency is believed to mainly result from the upregulation of mineral transporters in the absorptive villous cells, some other possibilities, such as PRL-enhanced crypt cell proliferation and differentiation to increase the absorptive area, have never been ruled out. Here, we investigated cell proliferation and mRNA expression of mineral absorption-related genes in the PRL-exposed IEC-6 crypt cells. As expected, the cell proliferation was not altered by PRL. Inasmuch as the mRNA expressions of villous cell markers, including dipeptidylpeptidase-4, lactase and glucose transporter-5, were not increased, PRL was not likely to enhance crypt cell differentiation into the absorptive villous cells. In contrast to the previous findings in villous cells, PRL was found to downregulate the expression of calbindin-D(9k), claudin-3 and occludin in IEC-6 crypt cells, while having no effect on transient receptor potential vanilloid family channels-5/6, plasma membrane Ca(2+)-ATPase (PMCA)-1b and Na(+)/Ca(2+) exchanger-1 expression. In conclusion, IEC-6 crypt cells did not respond to PRL by increasing proliferation or differentiation into villous cells. The present results thus supported the previous hypothesis that PRL enhanced mineral absorption predominantly by increasing transporter expression and activity in the absorptive villous cells.

  19. [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

    PubMed

    Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

    2015-08-01

    This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.

  20. Lgr5 positive stem cells sorted from small intestines of diabetic mice differentiate into higher proportion of absorptive cells and Paneth cells in vitro.

    PubMed

    Zhong, Xian-Yang; Yu, Tao; Zhong, Wa; Li, Jie-Yao; Xia, Zhong-Sheng; Yuan, Yu-Hong; Yu, Zhong; Chen, Qi-Kui

    2015-08-01

    Intestinal epithelial stem cells (IESCs) can differentiate into all types of intestinal epithelial cells (IECs) and Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a marker for IESC. Previous studies reported enhanced proliferation of IECs in diabetic mice. In this study, the in vitro differentiation of Lgr5 positive IESCs sorted from diabetic mice was further investigated. The diabetic mouse model was induced by streptozotocin (STZ), and crypt IECs were isolated from small intestines. Subsequently, Lgr5 positive IESCs were detected by flow cytometry (FCM) and sorted by magnetic activated cell sorting (MACS). Differentiation of the sorted IESCs was investigated by detecting the IEC markers in the diabetic mice using immunostaining, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), and Western blot analysis, which was compared with normal mice. We found that the proportion of Lgr5 positive cells in the crypt IECs of diabetic mice was higher than that of control mice (P < 0.05). Lgr5 positive IESCs could be significantly enriched in Lgr5 positive cell fraction sorted by MACS. Furthermore, the absorptive cell marker sucrase-isomaltase (SI) and the Paneth cell marker lysozyme 1 (Lyz1) were more highly expressed in the differentiated cells derived from Lgr5 positive IESCs of diabetic mice in vitro (P < 0.05). We demonstrate that the number of Lgr5 positive IESCs is significantly increased in the small intestines of STZ-induced diabetic mice. Lgr5 positive IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro. We characterized the expression of Lgr5 in the small intestine of diabetic mice, and sorted Lgr5 positive intestinal epithelial stem cells (IESCs) for investigating their differentiation in vitro. We proved that the quantity of Lgr5 positive IESCs was significantly increased in the small intestines of diabetic mice. IESCs sorted from the

  1. Oxalate deposition on asbestos bodies.

    PubMed

    Ghio, Andrew J; Roggli, Victor L; Richards, Judy H; Crissman, Kay M; Stonehuerner, Jacqueline D; Piantadosi, Claude A

    2003-08-01

    We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.

  2. Short communication: Casein hydrolysate and whey proteins as excipients for cyanocobalamin to increase intestinal absorption in the lactating dairy cow.

    PubMed

    Artegoitia, V M; de Veth, M J; Harte, F; Ouellet, D R; Girard, C L

    2015-11-01

    Bioavailability of vitamin B12 is low in humans and animals. Improving vitamin B12 absorption is important for optimal performance in dairy cows and for increasing vitamin B12 concentrations in milk for human consumption. However, when supplemented in the diet, 80% of synthetic vitamin B12, cyanocobalamin (CN-CBL), is degraded in the rumen of dairy cows and only 25% of the amount escaping destruction in the rumen disappears from the small intestine between the duodenal and ileal cannulas. In pigs, vitamin B12 from milk is more efficiently absorbed than synthetic CN-CBL. The objective of this study was to determine the efficacy of casein hydrolysate and whey proteins as excipients for CN-CBL to increase portal-drained viscera (PDV) flux of the vitamin in lactating dairy cows. Four multiparous lactating Holstein cows (237 ± 17 DIM) equipped with a rumen cannula and catheters in the portal vein and a mesenteric artery were used in a randomized Youden square design. They were fed every 2 h to maintain steady digesta flow. On experimental days, they received a postruminal bolus of (1) CN-CBL alone (0.1 g), (2) CN-CBL (0.1 g) + casein hydrolysate (10 g), or (3) CN-CBL (0.1 g) + whey proteins (10 g). Starting 30 min after the bolus, blood samples were taken simultaneously from the 2 catheters every 15 min during the first 2 h and then every 2 h until 24 h postbolus. Milk yield, DMI, and vitamin B12 portal-arterial difference and PDV flux were analyzed using the MIXED procedure of SAS. Milk yield and DMI were not affected by treatments. The portal-arterial difference of vitamin B12 during the 24-h period following the bolus of vitamin was greater when the vitamin was given in solution with casein hydrolysate (2.9 ± 4.6 pg/mL) than alone (-17.5 ± 5.2 pg/mL) or with whey protein (-13.4 ± 4.2 pg/mL). The treatment effects were similar for the PDV flux. The present results suggest that CN-CBL given with casein hydrolysate increases vitamin B12 absorption as compared with

  3. Acupuncture Improves Intestinal Absorption of Iron in Iron-deficient Obese Patients: A Randomized Controlled Preliminary Trial

    PubMed Central

    Xie, Xin-Cai; Cao, Yan-Qiang; Gao, Qian; Wang, Chen; Li, Man; Wei, Shou-Gang

    2017-01-01

    Background: Obesity has an adverse effect on iron status. Hepcidin-mediated inhibition of iron absorption in the duodenum is a potential mechanism. Iron-deficient obese patients have diminished response to oral iron therapy. This study was designed to assess whether acupuncture could promote the efficacy of oral iron supplementation for the treatment of obesity-related iron deficiency (ID). Methods: Sixty ID or ID anemia (IDA) patients with obesity were screened at Beijing Hospital of Traditional Chinese Medicine and were randomly allocated to receive either oral iron replacement allied with acupuncture weight loss treatment (acupuncture group, n = 30) or oral iron combined with sham-acupuncture treatment (control group, n = 30). Anthropometric parameters were measured and blood samples were tested pre- and post-treatment. Differences in the treatment outcomes of ID/IDA were compared between the two groups. Results: After 8 weeks of acupuncture treatment, there was a significant decrease in body weight, body mass index, waist circumference, and waist/hip circumference ratio of patients in the acupuncture group, while no significant changes were observed in the control group. Oral iron supplementation brought more obvious improvements of iron status indicators including absolute increases in serum iron (11.08 ± 2.19 μmol/L vs. 4.43 ± 0.47 μmol/L), transferrin saturation (11.26 ± 1.65% vs. 1.01 ± 0.23%), and hemoglobin (31.47 ± 1.19 g/L vs. 21.00 ± 2.69 g/L) in the acupuncture group than control group (all P < 0.05). Meanwhile, serum leptin (2.26 ± 0.45 ng/ml vs. 8.13 ± 0.55 ng/ml, P < 0.05) and hepcidin (3.52 ± 1.23 ng/ml vs. 6.77 ± 0.84 ng/ml, P < 0.05) concentrations declined significantly in the acupuncture group than those in the control group. Conclusion: Acupuncture-based weight loss can enhance the therapeutic effects of iron replacement therapy for obesity-related ID/IDA through improving intestinal iron absorption, probably by downregulating the

  4. High-performance inulin and oligofructose prebiotics increase the intestinal absorption of iron in rats with iron deficiency anaemia during the growth phase.

    PubMed

    Freitas, Karine de Cássia; Amancio, Olga Maria Silvério; de Morais, Mauro Batista

    2012-09-28

    Considering the high frequency of anaemia due to Fe deficiency, it is important to evaluate the effects of prebiotics on the absorption of Fe. The aim of the present study was to evaluate the effects of high-performance (HP) inulin, oligofructose and synergy1 during recovery from anaemia in rats through the intestinal absorption of Fe, food intake, body growth, caecal pH and weight of the intestine. Wistar rats (n 47) were fed with rations of AIN93-G with no Fe to induce Fe deficiency anaemia. At 36 d of life, anaemic rats were divided into four groups: (1) the HP inulin group; (2) the synergy1 group; and (3) the oligofructose group, all with 100 g of the respective prebiotic per kg of ration; and (4) a control group, in which the prebiotic was replaced by maize starch. Then, 25 mg of elemental Fe/kg of ration was added to all rations to allow recovery from anaemia. The final values of Hb in the HP inulin, synergy1, oligofructose and control groups were, respectively: 98 (94-99); 83 (81-92); 100 (90-114); 77 (72-81) g/l, with a statistically significant difference (P ≤ 0·001) between the oligofructose and control groups and the HP inulin and control groups. The four groups had an increase in weight and body length and had similar consumption of rations. The intestinal weight and caecal pH were significantly different between the groups that consumed prebiotics and the control group. HP inulin and oligofructose increased the intestinal absorption of Fe in rats.

  5. Intestinal Failure (Short Bowel Syndrome)

    MedlinePlus

    ... N Vitamin deficiencies as a result of poor absorption in the intestine N Electrolyte and mineral deficiencies ... N Kidney stones or gallstones due to poor absorption of calcium or bile How is intestinal failure ...

  6. Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism.

    PubMed

    Sugano, Kiyohiko

    2010-10-04

    The aqueous boundary layer (ABL) affects various aspects of oral absorption of a drug, from dissolution of the drug to the apparent K(m) value of intestinal wall metabolism and carrier mediated transport. However, the importance of ABL has often been entirely ignored in oral absorption investigation. In this minireview, the effect of ABL on oral absorption of a drug is discussed in an easy-to-understand manner. This review starts with an introduction of the boundary layer theory with many illustrations (and links to public web movies visualizing the ABL), and then discusses some specific cases of interest in pharmaceutical science, such as dissolution of floating drug particles in the USP paddle apparatus. The effect of the boundary layer on the membrane permeation is also discussed from the viewpoint of structure permeability relationship, carrier mediated transport/metabolism and estimation of the fraction of a dose absorbed for poor solubility compounds.

  7. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ileum. ...

  8. Villin promoter-mediated transgenic expression of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) increases intestinal calcium absorption in wild-type and vitamin D receptor knockout mice.

    PubMed

    Cui, Min; Li, Qiang; Johnson, Robert; Fleet, James C

    2012-10-01

    Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D-regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. TRPV6 transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X Flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was more than three-fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal 1α hydroxylase (CYP27B1) mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to <10% of WT but small intestine calbindin-D(9k) expression was elevated >15 times in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, low BMD, and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D(9K) mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR-independent upregulation of intestinal calbindin D(9k) in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. © 2012 American Society for Bone and Mineral Research.

  9. Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2: Effects on Intestinal Morphology and Absorption, Renal Function, Bone and Body Composition, and Muscle Function

    PubMed Central

    Jeppesen, P. B.; Lund, P.; Gottschalck, I. B.; Nielsen, H. B.; Holst, J. J.; Mortensen, J.; Poulsen, S. S.; Quistorff, B.; Mortensen, P. B.

    2009-01-01

    Background and aims. In a short-term study, Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. Methods. GLP-2, 400 micrograms, s.c.,TID, were offered, to eleven SBS patients keeping parenteral support constant. 72-hour nutritional balance studies were performed at baseline, weeks 13, 26, 52 during two years intermitted by an 8-week washout period. In addition, mucosal morphometrics, renal function (by creatinine clearance), body composition and bone mineral density (by DEXA), biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D), and muscle function (NMR, lungfunction, exercise test) were measured. Results. GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients, GLP-2 significantly reduced the fecal wet weight from approximately 3.0 to approximately 2.0 kg/day. This was accompanied by a decline in the oral wet weight intake, maintaining intestinal wet weight absorption and urinary weight constant. Renal function improved. No significant changes were demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. Conclusions. GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid and electrolyte absorption at lower oral intakes. This was accompanied by a 28% improvement in creatinine clearance. PMID:19707516

  10. Medical therapy, calcium oxalate urolithiasis

    NASA Technical Reports Server (NTRS)

    Ruml, L. A.; Pearle, M. S.; Pak, C. Y.

    1997-01-01

    The development of diagnostic protocols that identify specific risk factors for calcium oxalate nephrolithiasis has led to the formulation of directed medical regimens that are aimed at correcting the underlying metabolic disturbances. Initiation of these treatment programs has reduced markedly the rate of stone formation in the majority of patients who form stones. This article discusses the rationale that underlies the choice of medical therapy for the various pathophysiologic causes of calcium oxalate nephrolithiasis and the appropriate use of available medications.

  11. Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress.

    PubMed

    Jabri, Mohamed-Amine; Sakly, Mohsen; Marzouki, Lamjed; Sebai, Hichem

    2017-03-01

    The present study aimed to investigate the inhibitory effect of chamomile decoction extract (CDE) on intestinal glucose absorption as well as its protective role against high fat diet (HFD)-induced obesity and lipotoxicity in rats. We used the Ussing chamber system to investigate the effect of CDE on intestinal transport of glucose. Male Wistar rats were fed HFD for six weeks to provoke obesity. CDE (100mg/kg, b.w. p.o.) has been per orally administered to HFD fed rats. Ex vivo, we found that CDE significantly and dose-dependently increased intestinal absorption of glucose. In vivo, HFD increased the body, liver and kidney weights, while CDE treatment showed a significant protective effects. High fat diet induced also a lipid profiles disorder and a disturbances in kidney and liver function parameters. Moreover liver and kidney lipotoxicity is accompanied by an oxidative stress status characterized by increased lipoperoxidation, depletion of antioxidant enzymes activity and non-enzymatic antioxidant (-SH groups and GSH) levels as well as increased levels of free iron, hydrogen peroxide (H2O2) and calcium. However, treatment with CDE alleviated all the deleterious effects of HFD feed. These findings suggest that chamomile decoction extract can be used as functional beverage against obesity, hyperglycemia and hyperlipidemia.

  12. Oxalate content of cereals and cereal products.

    PubMed

    Siener, Roswitha; Hönow, Ruth; Voss, Susanne; Seidler, Ana; Hesse, Albrecht

    2006-04-19

    Detailed knowledge of food oxalate content is of essential importance for dietary treatment of recurrent calcium oxalate urolithiasis. Dietary oxalate can contribute considerably to the amount of urinary oxalate excretion. Because cereal foods play an important role in daily nutrition, the soluble and total oxalate contents of various types of cereal grains, milling products, bread, pastries, and pasta were analyzed using an HPLC-enzyme-reactor method. A high total oxalate content (>50 mg/100 g) was found in whole grain wheat species Triticum durum (76.6 mg/100 g), Triticum sativum (71.2 mg/100 g), and Triticum aestivum (53.3 mg/100 g). Total oxalate content was comparably high in whole grain products of T. aestivum, that is, wheat flakes and flour, as well as in whole grain products of T. durum, that is, couscous, bulgur, and pasta. The highest oxalate content was demonstrated for wheat bran (457.4 mg/100 g). The higher oxalate content in whole grain than in refined grain cereals suggests that oxalic acid is primarily located in the outer layers of cereal grains. Cereals and cereal products contribute to the daily oxalate intake to a considerable extent. Vegetarian diets may contain high amounts of oxalate when whole grain wheat and wheat products are ingested. Recommendations for prevention of recurrence of calcium oxalate stone disease have to take into account the oxalate content of these foodstuffs.

  13. Impact of peptide transporter 1 on the intestinal absorption and pharmacokinetics of valacyclovir after oral dose escalation in wild-type and PepT1 knockout mice.

    PubMed

    Yang, Bei; Hu, Yongjun; Smith, David E

    2013-10-01

    The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [³H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the C(max) and area under the curve (AUC)₀₋₁₈₀ of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the C(max) and AUC₀₋₁₈₀ of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10-100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy.

  14. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice.

    PubMed

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Weller, Curtis L; Carr, Timothy P; Park, Young-Ki; Lee, Ji-Young

    2015-11-01

    We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively.

  15. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice

    PubMed Central

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X.; Yang, Yue; Weller, Curtis L.; Carr, Timothy P.; Park, Young-Ki

    2015-01-01

    Abstract We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively. PMID:26161942

  16. Oxidative activation of acylguanidine prodrugs: intestinal presystemic activation in rats limits absorption and can be inhibited by co-administration of ketoconazole.

    PubMed

    Humphreys, W G; Obermeier, M T; Chong, S; Kimball, S D; Das, J; Chen, P; Moquin, R; Han, W-C; Gedamke, R; White, R E; Morrison, R A

    2003-01-01

    1. The disposition of acyl prodrugs was studied to improve the delivery of a guanidine-containing parent compound with poor membrane permeability and poor absorption. 2. The prodrugs were evaluated in vitro and in vivo for conversion to drug. Prodrugs were evaluated for hydrolytic or oxidative bioactivation in intestinal homogenate and rat liver S9 or microsomes. The disposition of the prodrugs in vivo was monitored in bile duct-cannulated rats. 3. Compounds with n-alkylacyl groups were efficiently bioactivated, but were hydrolysed before absorption. 4. Hydrolytic bioactivation could be blocked in vitro by branching in the alkyl chain. These compounds showed modest improvements in absorption, despite favourable permeability. Experiments with liver microsomes demonstrated efficient NADPH-dependent oxidative bioactivation, which was proposed to occur through a CYP-mediated side chain oxidation followed by cyclization and release of parent compound. Ketoconazole co-administration yielded approximately a twofold increase in absorption. 5. The hydrolytically stable prodrugs were successful in increasing absorption of parent drug and were efficiently bioactivated, but they did not yield increased systemic levels of drug.

  17. The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease

    PubMed Central

    Knight, John; Deora, Rajendar; Assimos, Dean G.; Holmes, Ross P.

    2013-01-01

    Oxalobacter formigenes is a unique intestinal organism that relies on oxalate degradation to meet most of its energy and carbon needs. A lack of colonization is a risk factor for calcium oxalate stone disease. Protection against calcium oxalate stone disease appears to be due to the oxalate degradation that occurs in the gut on low calcium diets with a possible further contribution from intestinal oxalate secretion. Much remains to be learned about how the organism establishes and maintains gut colonization and the precise mechanisms by which it modifies stone risk. The sequencing and annotation of the genomes of a Group 1 and a Group 2 strain of O. formigenes should provide the informatic tools required for the identification of the genes and pathways associated with colonization and survival. In this review we have identified genes that may be involved and where appropriate suggested how they may be important in calcium oxalate stone disease. Elaborating the functional roles of these genes should accelerate our understanding of the organism and clarify its role in preventing stone formation. PMID:23632911

  18. Effect of oxalic acid treatment on sediment arsenic concentrations and lability under reducing conditions.

    PubMed

    Sun, Jing; Bostick, Benjamin C; Mailloux, Brian J; Ross, James M; Chillrud, Steven N

    2016-07-05

    Oxalic acid enhances arsenic (As) mobilization by dissolving As host minerals and competing for sorption sites. Oxalic acid amendments thus could potentially improve the efficiency of widely used pump-and-treat (P&T) remediation. This study investigates the effectiveness of oxalic acid on As mobilization from contaminated sediments with different As input sources and redox conditions, and examines whether residual sediment As after oxalic acid treatment can still be reductively mobilized. Batch extraction, column, and microcosm experiments were performed in the laboratory using sediments from the Dover Municipal Landfill and the Vineland Chemical Company Superfund sites. Oxalic acid mobilized As from both Dover and Vineland sediments, although the efficiency rates were different. The residual As in both Dover and Vineland sediments after oxalic acid treatment was less vulnerable to microbial reduction than before the treatment. Oxalic acid could thus improve the efficiency of P&T. X-ray absorption spectroscopy analysis indicated that the Vineland sediment samples still contained reactive Fe(III) minerals after oxalic acid treatment, and thus released more As into solution under reducing conditions than the treated Dover samples. Therefore, the efficacy of enhanced P&T must consider sediment Fe mineralogy when evaluating its overall potential for remediating groundwater As.

  19. [Comparative studies on the enzymatic absorption of protein hydrolysates in the small intestine of the rat. 3. The absorption trypsins thermatatic and trypsin-thermatatic hydrolysates of a fava bean protein isolate compared to an equimolar mixture of free amino acids].

    PubMed

    Proll, J; Friedrich, M; Noack, J; Noack, R

    1985-01-01

    Tryptic, thermitatic, and tryptic-thermitatic Faba bean protein hydrolyzates as well as their equimolar mixture of amino acids were perfused through proximal and distal parts of the intestine (10 cm length) of non-narcotized rats. The total amino-acid concentration of the perfused solution was 50 mM. The absorption of nitrogen and total amino acids from the tryptic and tryptic-thermitatic hydrolyzates was lower than that from the amino-acid mixture, the absorption from the thermitatic hydrolyzate was in accordance with that from the amino-acid mixture. The absorption pattern of the amino acids which preferably undergo a peptidic absorption is similar with the three hydrolyzates: in the proximal intestinal part this concerns glutamic acid and serine, in the distal intestinal part--methionine, alanine, glycin, and serine. The absorption pattern of the amino acids is different between the three hydrolyzates and the amino-acid mixture. Between the absorption pattern of the amino acids from the three hydrolyzates little differences were evident only in the proximal intestinal part. The coefficients of variation of the tryptic-thermitatic hydrolyzates are in accordance with those of the amino-acid mixture, whereas that of the thermitatic hydrolyzates is significantly lower. In the distal intestinal part all supplied forms are more rapidly absorbed than in the proximal part of the intestine.

  20. Real-time monitoring of glucose and phenols intestinal absorption through an integrated Caco-2TC7cells/biosensors telemetric device: Hypoglycemic effect of fruit phytochemicals.

    PubMed

    Barberis, Antonio; Garbetta, Antonella; Cardinali, Angela; Bazzu, Gianfranco; D 'Antuono, Isabella; Rocchitta, Gaia; Fadda, Angela; Linsalata, Vito; D 'Hallewin, Guy; Serra, Andrea Pier; Minervini, Fiorenza

    2017-02-15

    An integrated device for real-time monitoring of glucose and phenols absorption, that consists of a sensors/biosensors system (SB) and a Caco-2TC7 human intestinal cell culture, is described in this study. The SB is composed of a glucose oxidase-based biosensor, a sentinel platinum sensor, a laccase/tyrosinase-based biosensor and a sentinel carbon sensor, all located in the basolateral compartment (BC) of a cell culture plate. Caco-2TC7 cells, differentiated on culture inserts, separated the apical compartment that simulates the intestinal lumen, from the BC which represented the bloodstream. The system recorded currents relative to glucose (1mM) absorption, obtaining bioavailability values (5.1%) comparable to HPLC analysis (4.8%). Phloridzin and phloretin, specific phenolic inhibitors of SGLT1 and GLUT2 glucose transporters, reduced the glucose transport of almost 10 times. They were minimally absorbed in the BC with a bioavailability of 0.13% and 0.49% respectively. The hypoglycemic potential of blueberry and pomegranate juices was also studied. In particular, the amount of glucose absorbed through the Caco-2TC7 monolayer was 8‰ for pomegranate and 1.7‰ for blueberry, demonstrating the potential hypoglycemic effect of the juices. Polyphenols absorption was also monitored by the SB and an increase was recorded during the first 50min in presence of both blueberry and pomegranate juices, then a constant decrease occurred. The proposed device has been developed as innovative tool for the dynamic monitoring of natural compounds effects on glucose absorption, in order to manage postprandial hyperglycemia.

  1. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    PubMed Central

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  2. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    PubMed

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.

  3. Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer.

    PubMed

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2016-02-01

    A human small intestinal epithelial cell (HIEC) monolayer was recently established in our laboratories as a novel system to evaluate the Papp (apparent permeability coefficient) of compounds during their absorption in humans. An effusion-based analysis using polyethylene glycol oligomers with molecular weights ranging from 194-898 indicated that HIEC and Caco-2 cell monolayers both had paracellular pores with 2 distinct radiuses (∼ 5 and 9-14 Å), whereas the porosity of large pores was 11-fold higher in the HIEC monolayer (44 × 10(-8)) than in the Caco-2 cells (4 × 10(-8)). A comparison between the fraction-absorbed (Fa) values observed in humans and those predicted from Papp values in both monolayers indicated that the HIEC monolayer had markedly higher precision to predict Fa values with root mean square error of 9.40 than the Caco-2 cells (root mean square error = 16.90) for 10 paracellularly absorbed compounds. Furthermore, the accuracy of the HIEC monolayer to classify the absorption of 23 test drugs with diverse absorption properties, including different pathways in the presence or absence of susceptibility to efflux transporters, was higher than that of the Caco-2 cell monolayer. In conclusion, the HIEC monolayer exhibited advantages over Caco-2 cells in the ranking and prediction of absorption of compounds in humans.

  4. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of (/sup 3/H)fucose into plasma membrane glycoproteins

    SciTech Connect

    Ellinger, A.; Pavelka, M.; Gangl, A.

    1983-12-01

    By means of radioautography the influence was tested of various periods (5, 15, 30, 40 min, 2 hr) of pretreatment with colchicine, administered intraperitoneally to rats at a dosage of 0.5 mg/100 g of body weight, on the intracellular pathway of (/sup 3/H)fucose in absorptive cells of the small intestine. Administration of colchicine for 30 min and longer time intervals causes delay in the insertion of (/sup 3/H)fucose into the oligosaccharide chains of glycoconjugates in the Golgi apparatus, and results in redistribution of the label apparent over the different portions of the plasma membrane. In controls, at 2 and 4 hr after administration of (/sup 3/H)fucose the apical plasma membrane is strongly labeled. Colchicine causes equalization of the reaction of apical and basolateral regions of the plasma membrane: the number of silver grains attributable to the apical plasma membrane is reduced; following treatment with colchicine, apical portions of the plasma membrane comprise 31.6 +/- 1.8% of the silver grains, 38.6 +/- 3.8% are attributable to basolateral membrane regions. The colchicine-induced equalization of the density of label of apical and basolateral regions of the plasma membrane, in addition to the occurrence of basolateral microvillus borders, suggests microtubules to be important in the maintenance of the polar organization of small intestinal absorptive cells.

  5. The bioavailability of calcium in spinach and calcium-oxalate to calcium-deficient rats.

    PubMed

    Kikunaga, S; Arimori, M; Takahashi, M

    1988-04-01

    We estimated the utilization of calcium in spinach and calcium-oxalate to calcium-deficient rats, and the effect of oxalic acid on absorption of dietary calcium by using calcium-deficient rats. The body weight gain of the calcium-deficient rats for 8 days receiving a calcium-deficient diet supplemented with raw-powdered spinach (R-sp), boiled-powdered spinach (B-sp), or calcium-oxalate (Ca-ox), and a control diet supplemented with oxalic acid (OX-C) were 4.8, 2.8, 4.9, and 5.1 g, respectively. The calcium content in the liver and kidney of the rats receiving R-sp, B-sp, Ca-ox, and OX-C diets significantly increased as compared with the calcium-deficient rats. Significant differences in the liver calcium levels were not observed among the rats receiving various additional diets, though the content in the kidneys of the rats receiving R-sp, B-sp, Ca-ox, and OX-C diets were 28.0, 21.5, 0.11, and 0.59 mg, respectively. An especially large amount of calcium was accumulated in the kidneys of the rats receiving R-sp and B-sp diets. The calcium concentration in the serum of the rats receiving Ca-ox and OX-C diets was higher than the calcium concentration in the serum of the R-sp, B-sp, and calcium-deficient rats. The calcium content in the left tibiae of the rats receiving Ca-ox and OX-C diets was higher than that of the rats receiving R-sp and B-sp diets. The breaking force of the right tibiae of the rats was highest in the OX-C group, and higher in the R-sp and Ca-ox groups than the breaking force of the right tibiae of the rats fed on B-sp diet. The alkaline phosphatase activity in the small intestines of the rats rose in the order of the R-sp, B-sp, and Ca-ox groups, although significant differences of the activity were not observed between the Ca-ox and the OX-C groups. The calcium retention of the rats receiving the calcium-deficient, R-sp, B-sp, Ca-ox, and OX-C diets was -18.5, 35.2, 25.6, 41.6, and 45.8%, respectively. About 35% of the calcium in the spinach was

  6. Comparison of a Computer Simulation Program and a Traditional Laboratory Practical Class for Teaching the Principles of Intestinal Absorption.

    ERIC Educational Resources Information Center

    Dewhurst, D. G.; And Others

    1994-01-01

    Evaluates the effectiveness of an interactive computer-assisted learning program for undergraduate students that simulates experiments performed using isolated, everted sacs of rat small intestine. The program is designed to offer an alternative student-centered approach to traditional laboratory-based practical classes. Knowledge gain of students…

  7. Coassimilation of dietary fat and benzo(a)pyrene in the small intestine: an absorption model using the killifish

    SciTech Connect

    Vetter, R.D.; Carey, M.C.; Patton, J.S.

    1985-04-01

    Benzo(a)pyrene (BP) was dissolved in dietary fat and fed in a single dose to killifish (Fundulus heteroclitus). Fluorescence microscopic examinations of small intestinal content and frozen sections of whole small intestine revealed that during fat digestion BP was codispersed in liquid crystalline product phases produced during lipolysis and then coabsorbed with dietary lipid followed by its reappearance in intracellular fat droplets. During the time that the absorbed fat remained in the enterocytes, BP fluorescence was initially concentrated in the intracellular fat droplets and then spread throughout the cytosol of the enterocytes. Tissue analyses showed that BP was rapidly metabolized in the intestine and transported to the gallbladder. These studies show that separation of a dissolved hydrophobic carcinogen from dietary fat occurs primarily after the fat has been digested, dispersed, absorbed, and reassembled in the enterocyte. The inability of the enterocyte to discriminate between dietary fat and dissolved carcinogenic compounds may be a partial explanation of the observed link between high fat diets and the incidence of some cancers. In vertebrates, the intestine and not the liver, appears to be the major site of metabolism of dietary polycyclic aromatic hydrocarbons (PAHs).

  8. Effect of the abrasive properties of sedges on the intestinal absorptive surface and resting metabolic rate of root voles.

    PubMed

    Wieczorek, Monika; Szafrańska, Paulina A; Labecka, Anna Maria; Lázaro, Javier; Konarzewski, Marek

    2015-01-15

    Recent studies on grasses and sedges suggest that the induction of a mechanism reducing digestibility of plant tissues in response to herbivore damage may drive rodent population cycles. This defence mechanism seems to rely on the abrasive properties of ingested plants. However, the underlying mechanism has not been demonstrated in small wild herbivores. Therefore, we carried out an experiment in which we determined the joint effect of abrasive sedge components on the histological structure of small intestine as well as resting metabolic rate (RMR) of the root vole (Microtus oeconomus). Histological examination revealed that voles fed with a sedge-dominated diet had shorter villi composed from narrower enterocytes in duodenum, jejunum and ileum. Reduction in the height of villi decreased along the small intestine. Activity of the mucus secretion increased along the small intestine and was significantly higher in the ileum. The intestinal abrasion exceeded the compensatory capabilities of voles, which responded to a sedge-dominated diet by a reduction of body mass and a concomitant decrease in whole body RMR. These results explain the inverse association between body mass and the probability of winter survival observed in voles inhabiting homogenous sedge wetlands.

  9. Genetically engineered Lactobacillus plantarum WCFS1 constitutively secreting heterologous oxalate decarboxylase and degrading oxalate under in vitro.

    PubMed

    Sasikumar, Ponnusamy; Gomathi, Sivasamy; Anbazhagan, Kolandaswamy; Baby, A Ebenezer; Sangeetha, J; Selvam, Govindan Sadasivam

    2014-11-01

    Hyperoxaluria is a major risk factor for urinary stone disease, where calcium oxalate (CaOx) is the most prevalent type of kidney stones. Systemic treatments of CaOx kidney stone patients are limited and comprise drawbacks including recurrence of stone formation and kidney damages. In the present work Lactobacillus plantarum (L. plantarum) was engineered to constitutively secrete oxalate decarboxylase (OxdC) for the degradation of intestinal oxalate. The homologous promoter PldhL and signal peptide Lp_0373 of L. plantarum were used for constructing recombinant vector pLdhl0373OxdC. Results showed that homologous promoter PldhL and signal peptide Lp_0373 facilitated the production, secretion, and functional expression of OxdC protein in L. plantarum. SDS-PAGE analysis revealed that 44 kDa protein OxdC was seen exceptionally in the culture supernatant of recombinant L. plantarum (WCFS1OxdC) harboring the plasmid pLdhl0373OxdC.The culture supernatant of L. plantarum WCFS1OxdC showed OxdC activity of 0.06 U/mg of protein, whereas no enzyme activity was observed in the supernatant of the wild type WCFS1 and the recombinant NC8OxdC strains. The purified recombinant OxdC from the WCFS1OxdC strain showed an activity of 19.1 U/mg protein. The recombinant L. plantarum strain secreted 25 % of OxdC protein in the supernatant. The recombinant strain degraded more than 70 % of soluble oxalate in the culture supernatant. Plasmid segregation analysis revealed that the recombinant strain lost almost 70-89 % of plasmid in 42nd and 84th generation, respectively. In conclusion, recombinant L. plantarum strain containing plasmid pLdhl0373OxdC showed constitutive secretion of bioactive OxdC and also capable of degrading externally available oxalate under in vitro conditions.

  10. The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat.

    PubMed

    Lowes, Simon; Haslam, Iain S; Fihn, Britt-Marie; Hilgendorf, Constanze; Karlsson, Johan E; Simmons, Nicholas L; Ungell, Anna-Lena

    2010-03-15

    The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN.

  11. Epithelial transport of noscapine across cell monolayer and influence of absorption enhancers on in vitro permeation and bioavailability: implications for intestinal absorption.

    PubMed

    Chougule, Mahavir B; Patel, Apurva R; Patlolla, Ram; Jackson, Tanise; Singh, Mandip

    2014-07-01

    The purpose of this study was to investigate the permeation of Noscapine (Nos) across the Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and to evaluate the influence of absorption enhancers on in vitro and in vivo absorption of Nos. The bidirectional transport of Nos was studied in Caco-2 and MDCK cell monolayers at pH 5.0-7.8. The effect of 0.5% w/v chitosan (CH) or Captisol (CP) on Nos permeability was investigated at pH 5.0 and 5.8. The effect of 1-5% w/v of CP on oral bioavailability of Nos (150 mg/kg) was evaluated in Sprague-Dawley rats. The effective permeability coefficients (Peff) of Nos across Caco-2 and MDCK cell monolayers was found to be in the order of pH 5.0 > 5.8 > 6.8 > 7.8. The efflux ratios of Peff < 2 demonstrated that active efflux does not limit the absorption of Nos. The use of CH or CP have shown significant (***, p < 0.001) enhancement in Peff of Nos across cell monolayer compared with the control group. The CP (1-5% w/v) based Nos formulations resulted in significant (***, p < 0.001) increase in the bioavailability of Nos compared with Nos solution. The use of CP represents viable approach for enhancing the oral bioavailability of Nos and reducing the required dose.

  12. Quantitation of countercurrent exchange during passive absorption from the dog small intestine: evidence for marked species differences in the efficiency of exchange.

    PubMed Central

    Bond, J H; Levitt, D G; Levitt, M D

    1977-01-01

    The present investigation was designed to quantitatively assess the possible influence of countercurrent exchange on passive absorption from the small intestine of the dog. Villus blood flow was measured with a modification of the microsphere method. Simultaneously, the absorption from the gut lumen of five diffusible gases (H2, He, CH4, 133Xe, and CO) was determined. Villus blood flow averaged 0.247 +/- 0.03 (SEM) ml/min per g. The observed absorption of H2, He, CH4, and 133Xe was only 16.2 +/- 1.8, 12.8 +/- 2.3, 12.0 +/- 1.8, and 15.8 +/- 1.4 %, respectively, of what this villus blood flow could carry away if it reached perfect equilibrium with the luminal gases. This low absorption rate could result from diffusion limitation to absorption or countercurrent exchange. The diffusive permeability of the barrier seperating the luminal gases and villus blood flow was assessed by measuring the absorption rate of CO. Because absorbed CO binds tightly to hemoglobin, it cannot exchange, and when present in low concentrations its uptake is entirely diffusion limited. Knowledge of the diffusion rate through tissue of the unbound gases relative to that of CO made it possible to calculate the degree to which each of the unbound gases should equilibrate with villus tip blood. The percentage equilibration between lumen and blood at the villus tip for H2, He, CH4, and 133Xe was 99.7, 99.9, 75.6, and 36.0% , respectively. Each of these values greatly exceeded the percentage equilibration of blood leaving the villus (calculated from the observed absorption rate and villus blood flow) and indicated an exchange of 83.8, 87.2, 84.1, and 56.1% of initially absorbed H2, He, CH4, and 133Xe. This result is in accord with theoretical calculations which suggest that countercurrent exchange should be exceedingly efficient in the dog. The striking effect of countercurrent exchange on passive absorption in the dog differs from our previous studies in the rabbit where no exchange was

  13. Modulation of NaCl absorption by [HCO3−] in the marine teleost intestine is mediated by soluble adenylyl cyclase

    PubMed Central

    Levin, Lonny R.; Buck, Jochen; Grosell, Martin

    2010-01-01

    Intestinal HCO3− secretion and NaCl absorption are essential for counteracting dehydration in marine teleost fish. We investigated how these two processes are coordinated in toadfish. HCO3− stimulated a luminal positive short-circuit current (Isc) in intestine mounted in Ussing chamber, bathed with the same saline solution on the external and internal sides of the epithelium. The Isc increased proportionally to the [HCO3−] in the bath up to 80 mM NaHCO3, and it did not occur when NaHCO3 was replaced with Na+-gluconate or with NaHCO3 in Cl−-free saline. HCO3− (20 mM) induced a ∼2.5-fold stimulation of Isc, and this [HCO3−] was used in all subsequent experiments. The HCO3−-stimulated Isc was prevented or abolished by apical application of 10 μM bumetanide (a specific inhibitor of NKCC) and by 30 μM 4-catechol estrogen [CE; an inhibitor of soluble adenylyl cyclase (sAC)]. The inhibitory effects of bumetanide and CE were not additive. The HCO3−-stimulated Isc was prevented by apical bafilomycin (1 μM) and etoxolamide (1 mM), indicating involvement of V-H+-ATPase and carbonic anhydrases, respectively. Immunohistochemistry and Western blot analysis confirmed the presence of an NKCC2-like protein in the apical membrane and subapical area of epithelial intestinal cells, of Na+/K+-ATPase in basolateral membranes, and of an sAC-like protein in the cytoplasm. We propose that sAC regulates NKCC activity in response to luminal HCO3−, and that V-H+-ATPase and intracellular carbonic anhydrase are essential for transducing luminal HCO3− into the cell by CO2/HCO3− hydration/dehydration. This mechanism putatively coordinates HCO3− secretion with NaCl and water absorption in toadfish intestine. PMID:20410468

  14. Role of Oxalic Acid Overexcretion in Transformations of Toxic Metal Minerals by Beauveria caledonica

    PubMed Central

    Fomina, M.; Hillier, S.; Charnock, J. M.; Melville, K.; Alexander, I. J.; Gadd, G. M.

    2005-01-01

    The fungus Beauveria caledonica was highly tolerant to toxic metals and solubilized cadmium, copper, lead, and zinc minerals, converting them into oxalates. This fungus was found to overexcrete organic acids with strong metal-chelating properties (oxalic and citric acids), suggesting that a ligand-promoted mechanism was the main mechanism of mineral dissolution. Our data also suggested that oxalic acid was the main mineral-transforming agent. Cadmium, copper, and zinc oxalates were precipitated by the fungus in the local environment and also in association with the mycelium. The presence of toxic metal minerals often led to the formation of mycelial cords, and in the presence of copper-containing minerals, these cords exhibited enhanced excretion of oxalic acid, which resulted in considerable encrustation of the cords by copper oxalate hydrate (moolooite). It was found that B. caledonica hyphae and cords were covered by a thick hydrated mucilaginous sheath which provided a microenvironment for chemical reactions, crystal deposition, and growth. Cryo-scanning electron microscopy revealed that mycogenic metal oxalates overgrew parental fungal hyphae, leaving a labyrinth of fungal tunnels within the newly formed mineral matter. X-ray absorption spectroscopy revealed that oxygen ligands played a major role in metal coordination within the fungal biomass during the accumulation of mobilized toxic metals by B. caledonica mycelium; these ligands were carboxylic groups in copper phosphate-containing medium and phosphate groups in pyromorphite-containing medium. PMID:15640211

  15. Determination of trace amount of oxalic acid with zirconium(IV)-(DBS-arsenazo) by spectrophotometry

    NASA Astrophysics Data System (ADS)

    Zhai, Qing-Zhou

    2008-11-01

    A novel method is proposed for the determination of trace amount of oxalic acid in the present article. In 1.0 M hydrochloric acid medium, oxalic acid can react with the zirconium(IV) in Zr(IV)-(DBS-arsenazo) complex and replaces the DBS-arsenazo to produce a hyperchromic effect at 520 nm. The hyperchromic degree is proportional to the concentration of the oxalic acid added over a defined range. Based on this property, a new method for the spectrophotometric determination of trace oxalic acid was developed. Beer's law is held over the concentration range of 9.0 × 10 -6 to 5.0 × 10 -4 M for oxalic acid with a correlation coefficient of 0.9995. The apparent molar absorptivity of the method is ɛ520 nm = 1.16 × 10 3 L mol -1 cm -1 and the detection limit for oxalic acid is 0.815 μg/mL. The developed method was directly applied to the determination of oxalic acid in tomato samples with satisfactory results.

  16. Determination of trace amount of oxalic acid with zirconium(IV)-(DBS-arsenazo) by spectrophotometry.

    PubMed

    Zhai, Qing-Zhou

    2008-11-15

    A novel method is proposed for the determination of trace amount of oxalic acid in the present article. In 1.0M hydrochloric acid medium, oxalic acid can react with the zirconium(IV) in Zr(IV)-(DBS-arsenazo) complex and replaces the DBS-arsenazo to produce a hyperchromic effect at 520 nm. The hyperchromic degree is proportional to the concentration of the oxalic acid added over a defined range. Based on this property, a new method for the spectrophotometric determination of trace oxalic acid was developed. Beer's law is held over the concentration range of 9.0 x 10(-6) to 5.0 x 10(-4)M for oxalic acid with a correlation coefficient of 0.9995. The apparent molar absorptivity of the method is epsilon520 nm = 1.16 x 10(3)L mol(-1)cm(-1) and the detection limit for oxalic acid is 0.815 microg/mL. The developed method was directly applied to the determination of oxalic acid in tomato samples with satisfactory results.

  17. Effects of 1α,25-Dihydroxyvitamin D3 on Intestinal Absorption and Disposition of Adefovir Dipivoxil and Its Metabolite, Adefovir, in Rats.

    PubMed

    Yoon, In-Soo; Son, Jun-Hyeng; Kim, Sang-Bum; Choi, Min-Koo; Maeng, Han-Joo

    2015-01-01

    The aim of this study was to investigate the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), an active form of vitamin D, on the oral absorption and disposition of adefovir dipivoxil (P-glycoprotein (P-gp) substrate) and its major active metabolite, adefovir (multidrug resistance-associated protein 4 (Mrp4) substrate), in rats. The pharmacokinetics of intravenous adefovir and oral adefovir dipivoxil was evaluated in control and 1,25(OH)2D3-treated rats. The intestinal absorption of adefovir dipivoxil was investigated through an in situ closed loop study, and the tissue distribution of adefovir after oral administration of adefovir dipivoxil was evaluated in the two groups. There was no significant difference in pharmacokinetic parameters of intravenous adefovir between the two groups. Importantly, the total area under the plasma concentration-time curve from time zero to time infinity (AUC), peak plasma concentration (Cmax) and extent of absolute oral bioavailability (F) of adefovir after oral administration of adefovir dipivoxil were significantly higher in 1,25(OH)2D3-treated rats than in control rats. In the in situ closed loop study, there was no significant difference in the remaining fraction of adefovir dipivoxil in the duodenum, jejunum and ileum loops between the two groups. In the tissue distribution study after oral administration of adefovir dipivoxil, the tissue-to-plasma partition coefficients of adefovir in the liver, brain, kidney, and intestine were significantly lower in the 1,25(OH)2D3-treated rats than in control rats. The present study indicates that 1,25(OH)2D3 treatment can enhance the oral absorption of adefovir dipivoxil, likely via the induction of basolateral Mrp4 function in rat intestine. However, the impact of 1,25(OH)2D3 treatment on the pharmacokinetics of intravenous adefovir was limited. These results could lead to further studies in clinically significant P-gp and/or MRP4-mediated 1,25(OH)2D3-drug interactions.

  18. An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine.

    PubMed

    Ikemura, Kenji; Inoue, Koichi; Mizutani, Hideki; Oka, Hisao; Iwamoto, Takuya; Okuda, Masahiro

    2012-09-05

    Oxidative stress is a critical mediator of various injuries following ischemia-reperfusion (I/R) associated with organ transplantation. Although oral bioavailability of cyclosporine A (CsA) was decreased by increased first-pass metabolism through CYP3A and P-glycoprotein (P-gp) specifically in the upper small intestine after liver I/R, the mechanism responsible for them remained to be clarified. In the present study, the effect of Trolox (an α-tocopherol analogue) on the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp after liver I/R and their regulations were investigated. Rats were subjected to 60 min of liver ischemia followed by 12h of reperfusion. Trolox was administered intravenously 5 min before reperfusion. Trolox diminished the increased malondialdehyde and total glutathione levels in plasma by liver I/R and concomitantly prevented the decreased area under the blood concentration-time curve of orally administered CsA as well as initial absorption rate of CsA from upper small intestine. The elevated CYP3A mRNA and activity in the upper small intestine as well as expression levels of P-gp in upper, middle, and lower small intestines after liver I/R were attenuated by Trolox administration. The elevations of CYP3A levels specifically in the upper small intestine of I/R rats were correlated with the lithocholic acid levels in the bile. These results demonstrate that Trolox ameliorates the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp by preventing oxidative stress, where the biliary lithocholic acid may be responsible for the elevated transcription of CYP3A specifically in the upper small intestine after liver I/R.

  19. Estimation of the oxalate content of foods and daily oxalate intake

    NASA Technical Reports Server (NTRS)

    Holmes, R. P.; Kennedy, M.

    2000-01-01

    BACKGROUND: The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate. METHODS: Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes. RESULTS: Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day. CONCLUSIONS: CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.

  20. Effects of oxalic acid on availability of zinc from spinach leaves and zinc sulfate to rats.

    PubMed

    Welch, R M; House, W A; Van Campen, D

    1977-06-01

    Some effects of dietary oxalic acid on availability of zinc from organic and inorganic sources were assessed. Male rats fed zinc-deficient diets with and without added sodium oxalate were orally dosed once with either 65Zn-labeled spinach leaves or 65Zn-labeled zinc sulfate. Spinach plants (Spinacia oleracea, var. "Winter Bloomsdale") were grown in 65Zn-labeled nutrient solutions that contained 0.033, 0.131 or 0.262 ppm zinc. Increasing zinc supply to the plants increased zinc concentration in the leaves. Oxalic acid content in all leaves was about 7% dry weight. Dietary oxalate enhanced the availability of 65Zn from zinc sulfate, but had no effect on absorption and retention of 65Zn from spinach leaves. Regardless of dietary oxalate levels, absorption and retention of 65Zn was greater from spinach leaves than from zinc sulfate. We concluded that endogenous zinc in spinach leaves was readily available to zinc-deficient rats, and that dietary oxalate was not deleterious to zinc availability.

  1. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: in vitro, in situ, in vivo and in silico studies.

    PubMed

    Yang, Cuiping; Zhang, Tianhong; Li, Zheng; Xu, Liang; Liu, Fei; Ruan, Jinxiu; Liu, Keliang; Zhang, Zhenqing

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22×10(-5) to 2.85×10(-5) cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (Cmax) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration-time curve (AUC0-12h) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug-drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC.

  2. Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans.

    PubMed

    Takahashi, Ryan H; Choo, Edna F; Ma, Shuguang; Wong, Susan; Halladay, Jason; Deng, Yuzhong; Rooney, Isabelle; Gates, Mary; Hop, Cornelis E C A; Khojasteh, S Cyrus; Dresser, Mark J; Musib, Luna

    2016-01-01

    The pharmacokinetics, metabolism, and excretion of cobimetinib, a MEK inhibitor, were characterized in healthy male subjects (n = 6) following a single 20 mg (200 μCi) oral dose. Unchanged cobimetinib and M16 (glycine conjugate of hydrolyzed cobimetinib) were the major circulating species, accounting for 20.5% and 18.3% of the drug-related material in plasma up to 48 hours postdose, respectively. Other circulating metabolites were minor, accounting for less than 10% of drug-related material in plasma. The total recovery of the administered radioactivity was 94.3% (±1.6%, S.D.) with 76.5% (±2.3%) in feces and 17.8% (±2.5%) in urine. Metabolite profiling indicated that cobimetinib had been extensively metabolized with only 1.6% and 6.6% of the dose remaining as unchanged drug in urine and feces, respectively. In vitro phenotyping experiments indicated that CYP3A4 was predominantly responsible for metabolizing cobimetinib. From this study, we concluded that cobimetinib had been well absorbed (fraction absorbed, Fa = 0.88). Given this good absorption and the previously determined low hepatic clearance, the systemic exposures were lower than expected (bioavailability, F = 0.28). We hypothesized that intestinal metabolism had strongly attenuated the oral bioavailability of cobimetinib. Supporting this hypothesis, the fraction escaping gut wall elimination (Fg) was estimated to be 0.37 based on F and Fa from this study and the fraction escaping hepatic elimination (Fh) from the absolute bioavailability study (F = Fa × Fh × Fg). Physiologically based pharmacokinetics modeling also showed that intestinal clearance had to be included to adequately describe the oral profile. These collective data suggested that cobimetinib was well absorbed following oral administration and extensively metabolized with intestinal first-pass metabolism contributing to its disposition.

  3. Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1.

    PubMed

    Okamura, Ayako; Koyanagi, Satoru; Dilxiat, Adila; Kusunose, Naoki; Chen, Jia Jun; Matsunaga, Naoya; Shibata, Shigenobu; Ohdo, Shigehiro

    2014-09-05

    Digested proteins are mainly absorbed as small peptides composed of two or three amino acids. The intestinal absorption of small peptides is mediated via only one transport system: the proton-coupled peptide transporter-1 (PepT1) encoded from the soluble carrier protein Slc15a1. In mammals, intestinal expression of PepT1/Slc15a1 oscillates during the daily feeding cycle. Although the oscillation in the intestinal expression of PepT1/Slc15a1 is suggested to be controlled by molecular components of circadian clock, we demonstrated here that bile acids regulated the oscillation of PepT1/Slc15a1 expression through modulating the activity of peroxisome proliferator-activated receptor α (PPARα). Nocturnally active mice mainly consumed their food during the dark phase. PPARα activated the intestinal expression of Slc15a1 mRNA during the light period, and protein levels of PepT1 peaked before the start of the dark phase. After food intake, bile acids accumulated in intestinal epithelial cells. Intestinal accumulated bile acids interfered with recruitment of co-transcriptional activator CREB-binding protein/p300 on the promoter region of Slc15a1 gene, thereby suppressing PPARα-mediated transactivation of Slc15a1. The time-dependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the intestinal expression of PepT1/Slc15a1 during the daily feeding cycle that led to circadian changes in the intestinal absorption of small peptides. These findings suggest a molecular clock-independent mechanism by which bile acid-regulated PPARα activity governs the circadian expression of intestinal peptide transporter.

  4. Effect of γ-aminobutyric acid on digestive enzymes, absorption function, and immune function of intestinal mucosa in heat-stressed chicken.

    PubMed

    Chen, Z; Xie, J; Wang, B; Tang, J

    2014-10-01

    To explore the effect of dietary γ-aminobutyric acid (GABA) on digestive enzyme activity, absorption function and immune function of intestinal mucosa in heat-stressed Wenchang chicken were studied. One-day-old male Wenchang chickens were randomly divided into a control group (CK), heat stress group (HS), and GABA+HS group. The chickens from the GABA+HS group were administered with 0.2 mL of GABA solution daily. Chickens from HS and GABA+HS groups were subjected to heat stress treatment at 40 ± 0.5°C for 2 h during 1300 to 1500 h every day. Blood was drawn and 0.5 cm-long duodenum, jejunum, and ileum were collected from the chickens on d 3, 5, 7, 9, 12, and 15. Results showed that the activity of Ca²⁺-Mg²⁺-adenosine triphosphatase (ATPase), Na⁺-K⁺-ATPase, maltase, sucrase, and alkaline phosphatase, the contents of secretory IgA, glutathione, and d-xylose, and the number of lymphocytes in HS group were significantly lower than those in the CK group. Among them, some were rescued after the treatment of GABA as the time extension. For maltase, d-xylose, alkaline phosphatase, and Na⁺-K⁺-ATPase, it required 5 to 7 d for achieving the significant effect. For sucrase, 12 d for the alleviation effect was required. In the case of other parameters, no alleviation was observed during the whole period of the study. We have concluded that HS can inhibit the activity of digestive enzymes and reduce absorption and immune functions of intestinal mucosa. γ-Aminobutyric acid can effectively alleviate these inhibitory effects.

  5. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. The objective of the study was to determine whether vitamin D increased calcium absorption. This was an experimental study. The study was conducted at a teaching hospital. Participants included 17 children with nutrit...

  6. Comparison of sulfuric and oxalic acid anodizing for preparation of thermal control coatings for spacecraft

    NASA Technical Reports Server (NTRS)

    Le, Huong G.; Watcher, John M.; Smith, Charles A.

    1988-01-01

    The development of thermal control surfaces, which maintain stable solar absorptivity and infrared emissivity over long periods, is challenging due to severe conditions in low-Earth orbit (LEO). Some candidate coatings are second-surface silver-coated Teflon; second-surface, silvered optical solar reflectors made of glass or quartz; and anodized aluminum. Sulfuric acid anodized and oxalic acid anodized aluminum was evaluated under simulated LEO conditions. Oxalic acid anodizing shows promise of greater stability in LEO over long missions, such as the 30 years planned for the Space Station. However, sulfuric acid anodizing shows lower solar absorptivity.

  7. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    SciTech Connect

    Yang, Cuiping Zhang, Tianhong Li, Zheng Xu, Liang Liu, Fei Ruan, Jinxiu Liu, Keliang Zhang, Zhenqing

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

  8. Formation of superconducting Bi sub 2-y Pb sub y Sr sub 2 Ca sub 2 Cu sub 3 O sub x from coprecipitated oxalates

    SciTech Connect

    Bernhard, K.; Gritzner, G.; Wang, Xianzhong; Baeuerle, D. )

    1990-06-01

    The conditions for the coprecipitation of Bi{sup 3+}, Pb{sup 2+}, Ca{sup 2+} as oxalates are reported. These oxalates were used as precursors for the formation of Bi{sub 2-y}Pb{sub y}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} superconducting ceramics. The behavior of the oxalates upon heat treatment was studied by thermogravimetry. Both the oxalates and the superconducting oxides were analyzed and characterized by atomic absorption spectroscopy and by X-ray diffraction.

  9. OXALATE FORMATION FROM GLYOXAL IN ERYTHROCYTES

    PubMed Central

    Knight, John; Wood, Kyle D.; Lange, Jessica N.; Assimos, Dean G.; Holmes, Ross P.

    2015-01-01

    OBJECTIVES To determine whether glyoxal can be converted to oxalate in human erythrocytes. Glyoxal synthesis is elevated in diabetes, cardiovascular disease and other diseases with significant oxidative stress. Erythrocytes are a good model system for such studies as they lack intracellular organelles and have a simplified metabolism. METHODS Erythrocytes were isolated from healthy volunteers and incubated with varying concentrations of glyoxal for different amounts of time. Metabolic inhibitors were used to help characterize metabolic steps. The conversion of glyoxal to glycolate and oxalate in the incubation medium was determined by chromatographic techniques. RESULTS The bulk of the glyoxal was converted to glycolate but ~1% was converted to oxalate. Inclusion of the pro-oxidant, menadione, in the medium increased oxalate synthesis, and the inclusion of disulfiram, an inhibitor of aldehyde dehydrogenase activity, decreased oxalate synthesis. CONCLUSIONS The glyoxalase system, which utilizes glutathione as a cofactor, converts the majority of the glyoxal taken up by erythrocytes to glycolate but a small portion is converted to oxalate. A reduction in intracellular glutathione increases oxalate synthesis and a decrease in aldehyde dehydrogenase activity lowers oxalate synthesis and suggests that glyoxylate is an intermediate. Thus, oxidative stress in tissues could potentially increase oxalate synthesis. PMID:26546809

  10. Absorption, Conjugation and Efflux of the Flavonoids, Kaempferol and Galangin, Using the Intestinal CACO-2/TC7 Cell Model.

    PubMed

    Barrington, Robert; Williamson, Gary; Bennett, Richard N; Davis, Barry D; Brodbelt, Jennifer S; Kroon, Paul A

    2009-01-01

    Flavonoids are biologically active compounds in food with potential health effects. We have used the Caco-2 cell monolayer model to study the absorption and metabolism of two flavonols, a class of flavonoids, specifically kaempferol and galangin. Metabolism experiments allowed identification of 5 kaempferol conjugates: 3-, 7- and 4'-glucuronide, a sulphate and a glucurono-sulphate; and 4 galangin conjugates: 3-, 5- and 7-glucuronides, and a sulphate, using specific enzyme hydrolysis, HPLC-MS, and HPLC with post column metal complexation/tandem MS. Transport studies showed that the flavonols were conjugated inside the cells then transported across the monolayer or effluxed back to the apical side. Sulphated conjugates were preferentially effluxed back to the apical side, whereas glucuronides were mostly transported to the basolateral side. For kaempferol, a small amount of the unconjugated aglycone permeated in both directions, indicating some passive diffusion. When kaempferol-3-glucuronide and quercetin7-sulphate were applied to either side of the cells, no permeation in either direction was observed, indicating that conjugates cannot re-cross the cell monolayer. Formation of apical kaempferol-7- and 4'-glucuronides was readily saturated, whereas formation of other conjugates at the apical side and all at the basolateral side increased with increasing concentration of kaempferol, implying different transporters are responsible at the apical and basolateral sides. The results highlight the important but complex metabolic changes occurring in flavonoids during absorption.

  11. Absorption, Conjugation and Efflux of the Flavonoids, Kaempferol and Galangin, Using the Intestinal CACO-2/TC7 Cell Model

    PubMed Central

    Barrington, Robert; Williamson, Gary; Bennett, Richard N; Davis, Barry D; Brodbelt, Jennifer S; Kroon, Paul A

    2009-01-01

    Flavonoids are biologically active compounds in food with potential health effects. We have used the Caco-2 cell monolayer model to study the absorption and metabolism of two flavonols, a class of flavonoids, specifically kaempferol and galangin. Metabolism experiments allowed identification of 5 kaempferol conjugates: 3-, 7- and 4′-glucuronide, a sulphate and a glucurono-sulphate; and 4 galangin conjugates: 3-, 5- and 7-glucuronides, and a sulphate, using specific enzyme hydrolysis, HPLC-MS, and HPLC with post column metal complexation/tandem MS. Transport studies showed that the flavonols were conjugated inside the cells then transported across the monolayer or effluxed back to the apical side. Sulphated conjugates were preferentially effluxed back to the apical side, whereas glucuronides were mostly transported to the basolateral side. For kaempferol, a small amount of the unconjugated aglycone permeated in both directions, indicating some passive diffusion. When kaempferol-3-glucuronide and quercetin7-sulphate were applied to either side of the cells, no permeation in either direction was observed, indicating that conjugates cannot re-cross the cell monolayer. Formation of apical kaempferol-7- and 4′-glucuronides was readily saturated, whereas formation of other conjugates at the apical side and all at the basolateral side increased with increasing concentration of kaempferol, implying different transporters are responsible at the apical and basolateral sides. The results highlight the important but complex metabolic changes occurring in flavonoids during absorption. PMID:20046888

  12. Transcriptional analysis of porcine intestinal mucosa infected with Salmonella Typhimurium revealed a massive inflammatory response and disruption of bile acid absorption in ileum.

    PubMed

    Uribe, Juber Herrera; Collado-Romero, Melania; Zaldívar-López, Sara; Arce, Cristina; Bautista, Rocío; Carvajal, Ana; Cirera, Susanna; Claros, M Gonzalo; Garrido, Juan J

    2016-01-07

    Infected pork meat is an important source of non-typhoidal human salmonellosis. Understanding of molecular mechanisms involved in disease pathogenesis is important for the development of therapeutic and preventive strategies. Thus, hereby we study the transcriptional profiles along the porcine intestine during infection with Salmonella Typhimurium, as well as post-transcriptional gene modulation by microRNAs (miRNA). Sixteen piglets were orally challenged with S. Typhimurium. Samples from jejunum, ileum and colon, collected 1, 2 and 6 days post infection (dpi) were hybridized to mRNA and miRNA expression microarrays and analyzed. Jejunum showed a reduced transcriptional response indicating mild inflammation only at 2 dpi. In ileum inflammatory genes were overexpressed (e.g., IL-1B, IL-6, IL-8, IL1RAP, TNFα), indicating a strong immune response at all times of infection. Infection also down-regulated genes of the FXR pathway (e.g., NR1H4, FABP6, APOA1, SLC10A2), indicating disruption of the bile acid absorption in ileum. This result was confirmed by decreased high-density lipoprotein cholesterol in serum of infected pigs. Ileal inflammatory gene expression changes peaked at 2 dpi and tended to resolve at 6 dpi. Furthermore, miRNA analysis of ileum at 2 dpi revealed 62 miRNAs potentially regulating target genes involved in this inflammatory process (e.g., miR-374 and miR-451). In colon, genes involved in epithelial adherence, proliferation and cellular reorganization were down-regulated at 2 and 6 dpi. In summary, here we show the transcriptional changes occurring at the intestine at different time points of the infection, which are mainly related to inflammation and disruption of the bile acid metabolism.

  13. The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

    PubMed

    González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

    2014-01-01

    An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p < 0.05) than ileal endogenous fluxes and total tract endogenous losses of Ca, but ileal endogenous fluxes were less (p < 0.05) than total tract endogenous losses. Standardised digestibility of Ca was not affected by the level of phytic acid, but decreased (p < 0.05) as Ca level increased in L. calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p < 0.05). The standardised duodenal digestibility (SDD), standardised ileal digestibility (SID) and standardised total tract digestibility (STTD) of Ca were not different if calcium carbonate was the source of dietary Ca. However, the STTD of Ca in L. calcareum Ca was greater (p < 0.05) than the SID and SDD of Ca. The SDD, SID and STTD of Ca in calcium carbonate were greater (p < 0.05) than those of L. calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly

  14. Measurements of oxalic acid, oxalates, malonic acid, and malonates in atmospheric particulates.

    PubMed

    Yang, Liming; Yu, Liya E

    2008-12-15

    This study systematically examined effects of analytical approaches on resultant concentrations of oxalic acid, oxalates, malonic acid, and malonates. Results demonstrated that employing separate water extraction and THF extraction is required to properly quantify dicarboxylic acids vs dicarboxylates using IC or GC-MS. Applications of the recommended methods to analyze PM2.5 collected in Singapore showed that concentrations of oxalate ranged from 361.4 to 481.4 ng m(-3), which were 10-14.7 times higher than that of oxalic acid. Unlike that of oxalates, malonate concentrations (10.5-23.4 ng m(-3)) were no more than half of malonic acid concentration (43.8-53.9 ng m(-3)) in PM2.5. Concentration ratios of oxalate-to-oxalic acid and malonate-to-malonic acid obtained from this work were applied to reported literature data; as a first approximation, in urban environments similar to that in Singapore, quantifiable oxalic acid, oxalates, malonic acid, and malonates in PM2.5 could range from 7.6 to 68.0, 82.2 to 732.8, 6.3 to 150, and 1.3 to 60 ng m(-3), respectively. Because photooxidation properties and hygroscopicity of dicarboxylic acids can substantially differ from that of dicarboxylates, more studies are needed to quantify ambient oxalic acid and malonic acid vs oxalates and malonates.

  15. Enabling the Intestinal Absorption of Highly Polar Anti-Viral Agents: Ion-Pair Facilitated Membrane Permeation of Zanamivir Heptyl Ester and Guanidino Oseltamivir

    PubMed Central

    Miller, Jonathan M.; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L.

    2012-01-01

    Anti-viral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability anti-viral agents zanamivr heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-napthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K11aq) of 388 M−1 for ZHE-HNAP and 2.91 M−1 for GO.-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (Papp) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial Papp (0.8 – 3.0 × 10−6 cm/s) was observed in the presence of 6–24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 Papp versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (Peff) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 × 10−5 cm/s with 10 mM HNAP, matching the Peff of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K11aq versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this work

  16. Association analysis for oxalate concentration in spinach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening and breeding low-oxalate germplasm is a major objective in spinach breeding. This research aims to conduct association analysis and identify SNP markers associated with oxalate concentration in spinach germplasm. A total of 310 spinach genotypes including 300 USDA germplasm accessions and ...

  17. Engineering calcium oxalate crystal formation in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many plants accumulate crystals of calcium oxalate. Just how these crystals form remains unknown. To gain insight into the mechanisms regulating calcium oxalate crystal formation, a crystal engineering approach was initiated utilizing the non-crystal accumulating plant, Arabidopsis. The success of t...

  18. Experimental oxalate urolith formation in rats.

    PubMed

    McIntosh, G H; Belling, G B; Bulman, F H

    1979-06-01

    Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.

  19. Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with α-linolenic acid and the transport mechanism of the conjugates.

    PubMed

    Xiao, Yuliang; Li, Pingli; Cheng, Yanna; Zhang, Xinke; Sheng, Juzheng; Wang, Decai; Li, Juan; Zhang, Qian; Zhong, Chuanqing; Cao, Rui; Wang, Fengshan

    2014-04-25

    The purpose of this report was to demonstrate the effect of amphiphilic polysaccharides-based self-assembling micelles on enhancing the oral absorption of low molecular weight chondroitin sulfate (LMCS) in vitro and in vivo, and identify the transepithelial transport mechanism of LMCS micelles across the intestinal barrier. α-Linolenic acid-low molecular weight chondroitin sulfate polymers(α-LNA-LMCS) were successfully synthesized, and characterized by FTIR, (1)HNMR, TGA/DSC, TEM, laser light scattering and zeta potential. The significant oral absorption enhancement and elimination half-life (t₁/₂) extension of LNA-LMCS2 in rats were evidenced by intragastric administration in comparison with CS and LMCS. Caco-2 transport studies demonstrated that the apparent permeability coefficient (Papp) of LNA-LMCS2 was significantly higher than that of CS and LMCS (p<0.001), and no significant effects on the overall integrity of the monolayer were observed during the transport process. In addition, α-LNA-LMCS micelles accumulated around the cell membrane and intercellular space observed by confocal laser scanning microscope (CLSM). Furthermore, evident alterations in the F-actin cytoskeleton were detected by CLSM observation following the treatment of the cell monolayers with α-LNA-LMCS micelles, which further certified the capacity of α-LNA-LMCS micelles to open the intercellular tight junctions rather than disrupt the overall integrity of the monolayer. Therefore, LNA-LMCS2 with low cytotoxicity and high bioavailability might be a promising substitute for CS in clinical use, such as treating osteoarthritis, atherosclerosis, etc.

  20. Effect of recombinant human growth hormone on intestinal absorption and body composition in children with short bowel syndrome.

    PubMed

    Goulet, Olivier; Dabbas-Tyan, Myriam; Talbotec, Cécile; Kapel, Nathalie; Rosilio, Myriam; Souberbielle, Jean-Claude; Corriol, Odile; Ricour, Claude; Colomb, Virginie

    2010-01-01

    This prospective study aimed to establish the effect of recombinant human growth hormone (rhGH) on intestinal function in children with short bowel syndrome (SBS). Eight children with neonatal SBS were included. All were dependent on parenteral nutrition (PN) for >3 years (range, 3.8-11.6 years), with PN providing >50% of recommended dietary allowance for age (range, 50%-65%). The subjects received rhGH (Humatrope) 0.13 mg/kg/d subcutaneously over a 12-week period. The follow-up was continued over a 12-month period after rhGH discontinuation. Clinical and biological assessments were performed at baseline, at the end of the treatment period, and 12 months after the end of treatment. No side effects related to rhGH were observed. PN requirements were decreased in all children during the course of rhGH treatment. Between baseline and the end of treatment, significant increases were observed in concentrations (mean ± standard deviation) of serum insulin-like growth factor 1 (103.1 ± 49.9 µg/L vs 153.5 ± 82.2 µg/L; P < .01), serum insulin-like growth factor-binding protein 3 (1.7 ± 0.6 mg/L vs 2.5 ± 0.9 mg/L; P < .001), and plasma citrulline (16.5 ± 14.8 µmol/L vs 25.2 ± 18.3 µmol/L; P < .05). A median 54% increase in enteral intake (range, 10%-244%) was observed (P < .001) and net energy balance improved significantly (P < .002). It was necessary for 6 children to be maintained on PN or restarted after discontinuation of rhGH treatment, and they remained on PN until the end of the follow-up period. A 12-week high-dose rhGH treatment allowed patients to decrease PN, but only 2 patients could be definitively weaned from PN. Indications and cost-effectiveness of rhGH treatment for SBS pediatric patients need further evaluation.

  1. Inclusion of ancient Latin-American crops in bread formulation improves intestinal iron absorption and modulates inflammatory markers.

    PubMed

    Laparra, José Moisés; Haros, Monika

    2016-02-01

    This study compares iron (Fe) absorption in Fe-deficient animals from bread formulations prepared by substitution of white wheat flour (WB) by whole wheat flour (WWB), amaranth flour (Amaranthus hypochondriacus, 25%) (AB) and quinoa flour (Chenopodium quinoa, 25%) (QB), or chia flour (Salvia hispanica L, 5%) (ChB). Hematological parameters of Fe homeostasis, plasmatic active hepcidin peptide production (LC coupled to Ms/Ms), and liver TfR-2 and IL-6 expression (RT-qPCR) were determined. The different bread formulations increased Fe content between 14% and 83% relative to white bread. Only animals fed with WWB, AB and ChB increased haemoglobin concentrations significantly. Feeding the different bread formulations did not increase hepcidin levels, but down-regulated transferrin receptor 2 (TfR2) (apart from WWB) and IL-6 (apart from QB) expression levels. Only AB and ChB had a significant influence on Fe bioavailability at the investigated level of substitution. The potential contribution of these flours would not differ considerably from that of WWB.

  2. Effects of a mixture of steam-flaked corn and extruded soybeans on performance, ruminal development, ruminal fermentation, and intestinal absorptive capability in veal calves.

    PubMed

    Xie, X X; Meng, Q X; Liu, P; Wu, H; Li, S R; Ren, L P; Li, X Z

    2013-09-01

    This study investigated the effects of a mixture of steam-flaked corn and extruded soybeans on performance, ruminal development, ruminal fermentation variables, and intestinal absorptive capability in Holstein male calves (n = 39). Calves were assigned to 1 of 3 treatments (13 calves per treatment): 1) milk replacer (MR), 2) one-half of the amount of MR in treatment 1, plus a mixture of 62.1% steam-flaked corn and 30.5% extruded soybeans provided ad libitum (HMCS), or 3) a mixture of 62.1% steam-flaked corn and 30.5% extruded soybeans provided ad libitum (CS). All the calves were started at 2 ± 1 d of age and studied for 150 d. Each 30 d was defined as 1 period. Dry matter intake and growth were measured daily and monthly, respectively. All calves were harvested at 150 d of age, after which rumen fluid was collected. Rumen and intestine samples were gathered. Calves fed MR exhibited greater BW (P = 0.001) and ADG (P < 0.001), compared with calves fed HMCS and CS from period 2 to 3; however, from period 4 to 5, CS calves had greater (P < 0.04) ADG than MR calves. The treatments did not differ in final BW (P = 0.72) and ADG (P = 0.20) from period 2 to 5. Compared with HMCS and MR calves, CS calves had the greatest DMI (P < 0.001) and the least feed efficiency (P < 0.001) from period 2 to 5. For ruminal fermentation parameters, CS calves had decreased (P = 0.04) rumen pH than MR calves. The NH3 concentrations were greater (P = 0.03) in calves fed HMCS than calves fed MR and CS. Total VFA concentrations were greatest in CS calves (P = 0.02). Calves fed CS had the greatest molar concentrations of propionate, butyrate, and valerate (P < 0.002), and calves fed HMCS had the greatest molar concentrations of isobutyrate (P = 0.001) and isovalerate (P = 0.001). The CS calves exhibited greater empty rumen weight (P = 0.001), papillae length (P < 0.001), papillae width (P < 0.001), rumen wall thickness (P = 0.012), and papillae density (P = 0.003). The greatest villus heights

  3. In vitro prediction of human intestinal absorption and blood-brain barrier partitioning: development of a lipid analog for micellar liquid chromatography.

    PubMed

    De Vrieze, Mike; Janssens, Pieter; Szucs, Roman; Van der Eycken, Johan; Lynen, Frédéric

    2015-09-01

    Over the past decades, several in vitro methods have been tested for their ability to predict either human intestinal absorption (HIA) or penetration across the blood-brain barrier (BBB) of drugs. Micellar liquid chromatography (MLC) has been a successful approach for retention time measurements of drugs to establish models together with other molecular descriptors. Thus far, MLC approaches have only made use of commercial surfactants such as sodium dodecyl sulfate (SDS) and polyoxyethylene (23) lauryl ether (Brij35), which are not representative for the phospholipids present in human membranes. Miltefosine, a phosphocholine-based lipid, is presented here as an alternative surfactant for MLC measurements. By using the obtained retention factors and several computed descriptors for a set of 48 compounds, two models were constructed: one for the prediction of HIA and another for the prediction of penetration across the BBB expressed as log BB. All data were correlated to experimental HIA and log BB values, and the performance of the models was evaluated. Log BB prediction performed better than HIA prediction, although HIA prediction was also improved a lot (from 0.5530 to 0.7175) compared to in silico predicted HIA values.

  4. CONCENTRATION OF Pu USING OXALATE TYPE CARRIER

    DOEpatents

    Ritter, D.M.; Black, R.P.S.

    1960-04-19

    A method is given for dissolving and reprecipitating an oxalate carrier precipitate in a carrier precipitation process for separating and recovering plutonium from an aqueous solution. Uranous oxalate, together with plutonium being carried thereby, is dissolved in an aqueous alkaline solution. Suitable alkaline reagents are the carbonates and oxulates of the alkali metals and ammonium. An oxidizing agent selected from hydroxylamine and hydrogen peroxide is then added to the alkaline solution, thereby oxidizing uranium to the hexavalent state. The resulting solution is then acidified and a source of uranous ions provided in the acidified solution, thereby forming a second plutoniumcarrying uranous oxalate precipitate.

  5. Artificial photosynthesis of oxalate and oxalate-based polymer by a photovoltaic reactor

    NASA Astrophysics Data System (ADS)

    Nong, Guangzai; Chen, Shan; Xu, Yuanjin; Huang, Lijie; Zou, Qingsong; Li, Shiqiang; Mo, Haitao; Zhu, Pingchuan; Cen, Weijian; Wang, Shuangfei

    2014-01-01

    A photovoltaic reactor was designed for artificial photosynthesis, based on the reactions involved in high energy hydrogen atoms, which were produced from water electrolysis. Water and CO2, under the conditions studied, were converted to oxalate (H2C2O4) and a polymer. This was the first time that the oxalates and oxalate-based polymer were produced from the artificial photosynthesis process.

  6. Artificial photosynthesis of oxalate and oxalate-based polymer by a photovoltaic reactor.

    PubMed

    Nong, Guangzai; Chen, Shan; Xu, Yuanjin; Huang, Lijie; Zou, Qingsong; Li, Shiqiang; Mo, Haitao; Zhu, Pingchuan; Cen, Weijian; Wang, Shuangfei

    2014-01-06

    A photovoltaic reactor was designed for artificial photosynthesis, based on the reactions involved in high energy hydrogen atoms, which were produced from water electrolysis. Water and CO2, under the conditions studied, were converted to oxalate (H2C2O4) and a polymer. This was the first time that the oxalates and oxalate-based polymer were produced from the artificial photosynthesis process.

  7. Artificial photosynthesis of oxalate and oxalate-based polymer by a photovoltaic reactor

    PubMed Central

    Nong, Guangzai; Chen, Shan; Xu, Yuanjin; Huang, Lijie; Zou, Qingsong; Li, Shiqiang; Mo, Haitao; Zhu, Pingchuan; Cen, Weijian; Wang, Shuangfei

    2014-01-01

    A photovoltaic reactor was designed for artificial photosynthesis, based on the reactions involved in high energy hydrogen atoms, which were produced from water electrolysis. Water and CO2, under the conditions studied, were converted to oxalate (H2C2O4) and a polymer. This was the first time that the oxalates and oxalate-based polymer were produced from the artificial photosynthesis process. PMID:24389750

  8. Reduction of plasma oxalate levels by oral application of Oxalobacter formigenes in 2 patients with infantile oxalosis.

    PubMed

    Hoppe, Bernd; Dittlich, Katalin; Fehrenbach, Henry; Plum, Georg; Beck, Bodo B

    2011-09-01

    The spectrum of primary hyperoxaluria type I is extremely heterogeneous, ranging from singular to recurrent urolithiasis and early end-stage renal disease (ESRD). In infantile oxalosis, the most devastating form, ESRD occurs as early as within the first weeks of life. No kidney replacement therapy sufficiently removes endogenously overproduced oxalate. However, curative combined liver-kidney transplant often is impracticable in small infants. Oxalobacter formigenes (O formigenes), an anaerobic oxalate-degrading bacterium, is a colonizer of the healthy human colon. Oral administration of O formigenes has been shown to significantly decrease urine and plasma oxalate levels in patients with primary hyperoxaluria. We report compassionate use of O formigenes in two 11-month-old girls with infantile oxalosis and ESRD. They received O formigenes twice a day for 4 weeks (or until transplant). Dialysis regimens were unchanged. Plasma oxalate levels decreased from >110 μmol/L before to 71.53 μmol/L under treatment in patient 1 and from >90 to 68.56 μmol/L (first treatment period) and 50.05 μmol/L (second treatment period) in patient 2. O formigenes was well tolerated. No serious side effects were reported. Extremely increased plasma oxalate levels in patients with infantile oxalosis may enable intestinal elimination of endogenous oxalate in the presence of O formigenes. Therefore, O formigenes therapy may be helpful as a bridging procedure until transplant in such patients.

  9. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants.

    PubMed

    Yang, J C; Loewus, F A

    1975-08-01

    l-Ascorbic acid-1-(14)C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants.

  10. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants 1

    PubMed Central

    Yang, Joan C.; Loewus, Frank A.

    1975-01-01

    l-Ascorbic acid-1-14C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants. PMID:16659288

  11. The interactive effect of phytase and coccidia on the gross lesions as well as the absorption capacity of intestine in broilers fed with diets low in calcium and available phosphorous.

    PubMed

    Mansoori, Behzad; Modirsanei, Mehrdad; Nodeh, Hassan; Rahbari, Sadegh

    2010-02-26

    In an experiment with 2x2 factorial design, the influence of dietary phytase on the intestinal lesions as well as the absorption capacity of intestine for D-xylose in broiler chickens provided with a diet low in calcium (Ca) and available phosphorus (aP) and challenged with Eimeria oocysts, was evaluated. Four groups of 20 1-day-old male broiler were provided with diets low in total Ca and aP (8 and 3g/kg instead of 10 and 5g/kg of Ca and aP in the diet, respectively). On day 10, 10 chicks from each group were randomly kept in individual raised floor wire cages to adopt environmental conditions. The experimental groups were as follows, Group 1: received no Eimeria oocysts (negative control), Group 2: received oocysts of mixed Eimeria species on day 15 to create an experimental coccidiosis (positive control), Group 3: negative control received phytase enzyme in their diet, from the first day of life, and Group 4: positive control received phytase enzyme in the diet. On day 20, after 12h fasting, the D-xylose absorption test was performed and immediately after that, the intestinal lesion scoring was carried out. The results showed that coccidiosis in Groups 2 and 4 produced progressive lesions in intestinal tract and reduced the concentration of plasma D-xylose in Group 2 when compared to Groups 1 and 3. Dietary phytase had no influence on the concentration of plasma D-xylose in un-infected birds. The enzyme had no influence on the intestinal lesions caused by coccidiosis as well. However, it increased the plasma D-xylose concentration of Group 4 to the level that it was comparable with Groups 1 and 3, at 45 and 90min post-ingestion of the solution. It was concluded that the addition of phytase enzyme to the low Ca and aP diet, increased indirectly the absorption capacity of intestine for D-xylose in infected chickens most probably through the improvement of mechanisms involved in the absorption and transport of D-xylose.

  12. Chaga mushroom-induced oxalate nephropathy.

    PubMed

    Kikuchi, Yuko; Seta, Koichi; Ogawa, Yayoi; Takayama, Tatsuya; Nagata, Masao; Taguchi, Takashi; Yahata, Kensei

    2014-06-01

    Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

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

    PubMed

    Pavelka, M; Ellinger, A

    1985-09-01

    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.

  14. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis

    PubMed Central

    Massart, J; Robin, MA; Noury, F; Fautrel, A; Lettéron, P; Bado, A; Eliat, PA; Fromenty, B

    2012-01-01

    BACKGROUND AND PURPOSE Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes. EXPERIMENTAL APPROACH Pentoxifylline (100 mg·kg−1·day−1) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT-PCR and Western blotting. KEY RESULTS Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline-treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver. CONCLUSION AND IMPLICATIONS Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long-term treatment with pentoxifylline could worsen fatty liver in some patients with pre-existing hyperglycaemia. PMID:21740407

  15. Spectroscopic study of the inhibition of calcium oxalate calculi by Larrea tridentata

    NASA Astrophysics Data System (ADS)

    Pinales, Luis Alonso

    The causes of urolithiasis include such influences as diet, metabolic disorders, and genetic factors which have been documented as sources that aggravate urinary calculi depositions and aggregations, and, implicitly, as causes of urolithiasis. This study endeavors to detail the scientific mechanisms involved in calcium oxalate calculi formation, and, more importantly, their inhibition under growth conditions imposed by the traditional medicinal approach using the herbal extract, Larrea tridentata. The calculi were synthesized without and with Larrea tridentata infusion by employing the single diffusion gel technique. A visible decrease in calcium oxalate crystal growth with increasing amounts of Larrea tridentata herbal infusion was observed in photomicrographs, as well as a color change from white-transparent for pure crystals to light orange-brown for crystals with inhibitor. Analysis of the samples, which includes Raman, infrared absorption, scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) techniques, demonstrate an overall transition in morphology of the crystals from monohydrate without herbal extract to dihydrate with inhibitor. Furthermore, the resulting data from Raman and infrared absorption support the possibilities of the influences, in this complex process, of NDGA and its derivative compounds from Larrea tridentata, and of the bonding of the magnesium of the inhibitor with the oxalate ion on the surface of the calculi crystals. This assumption corroborates well with the micrographs obtained under higher magnification, which show that the separated small crystallites consist of darker brownish cores, which we attribute to the dominance of growth inhibition by NDGA, surrounded by light transparent thin shells, which possibly correspond to passivation of the crystals by magnesium oxalate. The SEM results reveal the transformation from the dominant monoclinic structure of the calcium oxalate crystals grown alone to the tetragonal

  16. The adsorption and photo-degradation of oxalic acid at the TiO2 surface.

    NASA Astrophysics Data System (ADS)

    Mendive, Cecilia; Blesa, Miguel; Bahnemann, Detlef

    2006-03-01

    Oxalic acid is the simplest model compound to study the heterogeneous photocatalytic oxidation of pollutants on TiO2 containing more than one carboxylate group. We have carried out a study of a system of an oxalic acid solution in contact with a thin film of TiO2 particles employing ATR - FTIR in combination with quantum chemical calculations. Thus, possible adsorption structures have been identified and molecular dynamic simulations have been used to compare their predictions with the experimental data. It was found that the adsorption of oxalic acid on TiO2 in the dark can be explained in terms of two surface complexation modes for the anatase phase and only one surface complexation mode for the rutile phase. We have found that under illumination one of the complexes on the anatase phase preferably undergoes photo-degradation. At the same time water molecules are desorbed from the TiO2 surface by a thermal mechanism induced by the absorption of photons. Both processes favor the adsorption of more molecules of oxalic acid at the TiO2 surface which is thus enriched in the second complexation mode. A similar mechanism was found to occur on the rutile phase. The only complexation mode appears not to be photo-sensitive but the TiO2 surface is enriched in oxalic acid under illumination due to the replacement of photo-desorbed water molecules.

  17. Increased calcium bioavailability in mice fed genetically engineered plants lacking calcium oxalate.

    PubMed

    Morris, Jay; Nakata, Paul A; McConn, Michele; Brock, Amanda; Hirschi, Kendal D

    2007-07-01

    Bioavailable calcium affects bone formation and calcification. Here we investigate how a single gene mutation altering calcium partitioning in the model forage crop Medicago truncatula affects calcium bioavailability. Previously, the cod5 M. truncatula mutant was identified which contains identical calcium concentrations to wild-type, but contains no oxalate crystals. In this study, equal number of male and female mice were randomly grouped and then fed one of four 45Ca-containing diets: M. truncatula extrinsically or intrinsically labeled, and cod5 extrinsically or intrinsically labeled. Absorption of the tracer was determined in the legs one day after consumption. The absorption was similar in the M. truncatula and cod5 extrinsically labeled diets; however, in the intrinsically labeled diets, calcium absorption was 22.87% (P < 0.001) higher in mice fed cod5. Our study presents the first genetic evidence demonstrating the nutritional impact of removing oxalate crystals from foods.

  18. Metabolism of Fructose to Oxalate and Glycolate

    PubMed Central

    Knight, J.; Assimos, D. G.; Easter, L.; Holmes, R. P.

    2011-01-01

    Much attention has been recently directed at fructose consumption because of its association with obesity and subsequent development of chronic diseases. It was recently reported that an increased fructose intake increases the risk of forming kidney stones. It was postulated that fructose consumption may increase urinary oxalate, a risk factor for calcium oxalate kidney stone disease. However, conflicting results have been obtained in human studies examining the relationship between fructose metabolism and oxalate synthesis. To test whether fructose intake influences urinary excretions impacting kidney stone risk, healthy subjects consumed diets controlled in their contents of fructose, oxalate, calcium, and other nutrients. Subjects consumed diets containing 4, 13, and 21% of calories as fructose in a randomized order. No changes in the excretions of oxalate, calcium, and uric acid were observed. In vitro investigations with cultured liver cells incubated with 13C-labeled sugars indicated that neither fructose nor glucose was converted to oxalate by these cells. Fructose metabolism accounted for 12.4 ± 1.6% of the glycolate detected in the culture medium and glucose 6.4 ± 0.9%. Our results suggest that mechanisms for stone risk associated with fructose intake may lie in factors other than those affecting the major stone risk parameters in urine. PMID:20842614

  19. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  20. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Hu, David

    2015-11-01

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  1. Site-specific drug delivery to the middle-to-lower region of the small intestine reduces food-drug interactions that are responsible for low drug absorption in the fed state.

    PubMed

    Tanno, Fumié K; Sakuma, Shinji; Masaoka, Yoshie; Kataoka, Makoto; Kozaki, Toshio; Kamaguchi, Ryosei; Ikeda, Yutaka; Kokubo, Hiroyasu; Yamashita, Shinji

    2008-12-01

    Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effects). We designed enteric-coated tablets that start to disintegrate when they reach the middle-to-lower region of the small intestine, and examined whether they could reduce negative food effects in dogs. Tablets containing trientine as a model drug were coated with hypromellose acetate succinate (HPMCAS) with various values of succinoyl group content. The time lag of drug dissolution from these enteric-coated tablets in simulated intestinal fluid of pH 6.8 increased as the succinoyl group content was decreased. The AUC of trientine after oral administration of its aqueous solution to fed dogs was one-eighth of that in fasted dogs. The low drug absorption in fed dogs was improved when trientine was administered as enteric-coated tablets. The average ratio of AUC in the fed state to that in the fasted state increased with decreasing succinoyl group content of HPMCAS. Negative food effects completely disappeared after oral administration of tablets coated with HPMCAS having a succinoyl group content of 6.2% or less, which probably disintegrated in the middle-to-lower small intestine. Our results indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.

  2. High-fat diet intake from senescence inhibits the attenuation of cell functions and the degeneration of villi with aging in the small intestine, and inhibits the attenuation of lipid absorption ability in SAMP8 mice.

    PubMed

    Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu; Tsuduki, Tsuyoshi

    2015-11-01

    We examined the effect of a high-fat diet from senescence as a means of preventing malnutrition among the elderly. The senescence-accelerated mouse P8 was used and divided into three groups. The 6C group was given a normal diet until 6 months old. The 12N group was given a normal diet until 12 months old. The 12F group was given a normal diet until 6 months old and then a high-fat diet until 12 months old. In the oral fat tolerance test, there was a decrease in area under the curve for serum triacylglycerol level in the 12N group and a significant increase in the 12F group, suggesting that the attenuation of lipid absorption ability with aging was delayed by a high-fat diet from senescence. To examine this mechanism, histological analysis in the small intestine was performed. As a result, the degeneration of villi with aging was inhibited by the high-fat diet. There was also a significant decrease in length of villus in the small intestine in the 12N group and a significant increase in the 12F group. The high-fat diet from senescence inhibited the degeneration of villi with aging in the small intestine, and inhibited the attenuation of lipid absorption ability.

  3. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women.

    PubMed

    Hansen, Karen E; Nabak, Andrea C; Johnson, Rachael Erin; Marvdashti, Sheeva; Keuler, Nicholas S; Shafer, Martin M; Abrams, Steven A

    2014-04-01

    Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ≥6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 ± 8 y with a dietary magnesium intake of 345 ± 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ∼23 mg of oral ²⁶Mg and ∼11 mg of i.v. ²⁵Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 ± 5 y with a dietary magnesium intake of 325 ± 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 ± 0.08. The 72-h MgA correlated most highly with 0-24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0-24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (-0.003, P = 0.82) using means of the 0-24 h urine and 3-h serum MgA values. We conclude that means of 0-24 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection.

  4. Thermal degradation of aqueous oxalate species

    SciTech Connect

    Crossey, L.J. )

    1991-06-01

    The aqueous thermal degradation of oxalic acid (a naturally occurring dicarboxylic acid) and its anions has been examined experimentally under variable conditions of temperature (160-230C), time (24-96 h), buffered pH (4-7), and ionic strength (0.2-0.5 M). Decomposition of oxalate species follows a first-order rate law. Degradation rate increases with decreasing pH; the effects of ionic strength are not significant. Changes in reaction rate over the temperature range studied give activation energies that range from 29-50 kcal/mol over a starting solution pH range of 5-7. Extrapolation of these data to sedimentary basin temperatures suggests that oxalate species may be long-lived in formation waters. At 80C, half-lives range from 2,500 to 28,000 years at pH values of 5 and 7, respectively. Formate species are relatively stable degradation products over the range of conditions studied. Comparison of these data are relatively stable degradation products over the range of conditions studied. Comparison of these data with results of other thermal degradation studies of carboxylic acids and their anions indicate that acetate stability {much gt} formate stability > oxalate stability > gallate and malonate stability. These results are consistent with the high concentrations of acetate relative to oxalate and malonate observed in formation waters.

  5. Early postnatal kinetics of colostral immunoglobulin G absorption in fed and fasted piglets and developmental expression of the intestinal immunoglobulin G receptor.

    PubMed

    Cabrera, R; Lin, X; Ashwell, M; Moeser, A; Odle, J

    2013-01-01

    The transport of IgG across the epithelial barrier and into the circulation is achieved in part by the neonatal Fc receptor (FcRn), and this provides passive immunity to the neonate. The objective of this study was to determine the effect of time and feeding state on IgG absorption, intestinal morphology, and expression of IgG receptors in the first 24 h postbirth. Twenty newborn pigs were obtained immediately after birth and fitted with umbilical arterial catheters. Colostrum was manually collected from 12 lactating sows and centrifuged to produce defatted colostrum. Piglets were orally gavaged with 32 mL defatted colostrum per kilogram of BW (given in 2 doses 1 h apart) either at birth (0 h) or at 12 h postbirth under either fed (milk replacer) or fasted (saline solution) condition (n=5 per treatment). A fifth reference group (n=5) was euthanized at birth. Blood was collected every hour for the first 2 h immediately after the catheter was inserted and then every 4 h until 12 h (i.e., 0, 1, 2, 4, 8, and 12 h) for the treatment in which the defatted colostrum was given right after birth. For the treatment gavaged at 12 h postbirth, the sampling schedule was at 12, 13, 14, 16, 20, and 24 h. At 12 h postgavage, pigs were euthanized and jejunum tissues were collected for measurement of villi height, width, crypt depth, and gene expression of FcRn and β2-microglobulin (β2M) via reverse transcription PCR. Pig serum IgG concentration was determined by radial immunodiffusion. Data were analyzed according to a 2×2 factorial arrangement of treatments (0 h-fed, 0 h-fasted, 12 h-fed, and 12 h-fasted). There was no interaction between the time (age) of offering defatted colostrum (0 vs. 12 h) and nutritional state (fed vs. fasted) for any of the measurements, and there were no differences between fed and fasted pigs. Serum IgG concentrations increased progressively with time. Piglets offered defatted colostrum at 0 h had greater (P<0.05) overall IgG absorption and greater

  6. Heterogeneous photochemistry of oxalic acid on Mauritanian sand and Icelandic volcanic ash.

    PubMed

    Styler, Sarah A; Donaldson, D J

    2012-08-21

    Teragram quantities of crustal and volcanic aerosol are released into the atmosphere on an annual basis. Although these substrates contain photoactive metal oxides, little is known about the role that they may play in catalyzing the heterogeneous phototransformation of semivolatile organic species. In the present study, we have investigated oxalic acid photochemistry at the surface of Fe(2)O(3), TiO(2), Mauritanian sand, and Icelandic volcanic ash in the presence and absence of oxygen using a photochemical Knudsen cell reactor. Illumination of all sample types resulted in the production of gas-phase CO(2). In the case of Mauritanian sand, the production of gas-phase CO(2) scaled with the loss of surface oxalic acid. In the absence of oxygen, the production of CO(2) by the sand and ash films scaled with the absorption spectrum of iron oxalate, which suggests that the reaction is at least in part iron-mediated. The presence of oxygen suppressed CO(2) production at the Fe(2)O(3) surface, enhanced CO(2) production at the Mauritanian sand surface, and did not have a net effect upon CO(2) production at the Icelandic ash surface. These different oxygen dependencies imply that oxalic acid photochemistry at the authentic surfaces under study was not solely iron-mediated. Experiments at the TiO(2) surface, which showed enhanced CO(2) production from oxalic acid in the presence of oxygen, suggest that Ti-mediated photochemistry played an important role. In summary, these results provide evidence that solid-phase aerosol photochemistry may influence the atmospheric lifetime of oxalic acid in arid regions, where its removal via wet deposition is insignificant.

  7. ADVANCED OXIDATION: OXALATE DECOMPOSITION TESTING WITH OZONE

    SciTech Connect

    Ketusky, E.; Subramanian, K.

    2012-02-29

    At the Savannah River Site (SRS), oxalic acid is currently considered the preferred agent for chemically cleaning the large underground Liquid Radioactive Waste Tanks. It is applied only in the final stages of emptying a tank when generally less than 5,000 kg of waste solids remain, and slurrying based removal methods are no-longer effective. The use of oxalic acid is preferred because of its combined dissolution and chelating properties, as well as the fact that corrosion to the carbon steel tank walls can be controlled. Although oxalic acid is the preferred agent, there are significant potential downstream impacts. Impacts include: (1) Degraded evaporator operation; (2) Resultant oxalate precipitates taking away critically needed operating volume; and (3) Eventual creation of significant volumes of additional feed to salt processing. As an alternative to dealing with the downstream impacts, oxalate decomposition using variations of ozone based Advanced Oxidation Process (AOP) were investigated. In general AOPs use ozone or peroxide and a catalyst to create hydroxyl radicals. Hydroxyl radicals have among the highest oxidation potentials, and are commonly used to decompose organics. Although oxalate is considered among the most difficult organic to decompose, the ability of hydroxyl radicals to decompose oxalate is considered to be well demonstrated. In addition, as AOPs are considered to be 'green' their use enables any net chemical additions to the waste to be minimized. In order to test the ability to decompose the oxalate and determine the decomposition rates, a test rig was designed, where 10 vol% ozone would be educted into a spent oxalic acid decomposition loop, with the loop maintained at 70 C and recirculated at 40L/min. Each of the spent oxalic acid streams would be created from three oxalic acid strikes of an F-area simulant (i.e., Purex = high Fe/Al concentration) and H-area simulant (i.e., H area modified Purex = high Al/Fe concentration) after nearing

  8. Inflammation neither increases hepatic hepcidin nor affects intestinal (59)Fe-absorption in two murine models of bowel inflammation, hemizygous TNF(ΔARE/+) and homozygous IL-10(-/-) mice.

    PubMed

    Buffler, M; Becker, C; Windisch, W; Schümann, K

    2015-10-01

    Hepcidin-synthesis was reported to be stimulated by inflammation. In contrast, hepcidin synthesis was inhibited by TNFα and serum hepcidin was low. To elucidate these contradictions, we compare data on hepcidin expression, on iron absorption and homoeostasis and markers of inflammation between two murine models of intestinal inflammation and corresponding wild-types as determined by standard methods. In TNF(ΔARE/+) and IL-10(-/-)-mice hepatic hepcidin expression and protein content was significantly lower than in corresponding wild-types. However, (59)Fe whole-body retention showed no difference between knock-outs and corresponding wild-types 7d after gavage, in neither strain. Compared to wild-types, body weight, hepatic non-haem iron content, hemoglobin and hematocrit were significantly decreased in TNF(ΔARE/+) mice, while erythropoiesis increased. These differences were not seen in IL-10(-/-) mice. Duodenal IL-6 and TNFα content increased significantly in TNF(ΔARE/+) mice, while ferritin-H decreased along with hepatic hepcidin expression, ferritin L, and non-haem iron. In IL-10(-/-) mice, these changes were less marked or missing for non-haem iron. Duodenal ferritin-L and ferroportin increased significantly, while HFE decreased. Our results corroborate the conflicting combination of low hepcidin with inflammation and without increased intestinal iron absorption. Speculating on underlying mechanism, decreased hepcidin may result from stimulated erythropoiesis. Unaltered intestinal iron-absorption may compromise between the stimulation by increased erythropoiesis and inhibition by local and systemic inflammation. The findings suggest intense interaction between counterproductive mechanisms and ask for further research.

  9. Global impacts of multiphase oxalate production

    NASA Astrophysics Data System (ADS)

    Tost, Holger; Taraborrelli, Domenico

    2013-04-01

    Fine mode atmospheric aerosols are dominated by the organic fraction. A large fraction of these organic compounds consists of oxalates and carboxylic acids. Some of these compounds are produced in the gas phase and then subsequently partition into aerosol particles whereas others are produced directly in the aqueous phase in either cloud droplets or deliquesced aerosol particles. In this study we investigate the contribution of oxalates to the global organic aerosol burden using a comprehensive atmospheric chemistry general circulation model including explicit multiphase chemistry schemes for clouds and aerosols. For that purpose the aqueous phase chemistry has been augmented by a mechanism for oxalates, combined with a consistent gas phase chemistry of corresponding oxidation products from isoprene degradation. Using these tools we will present an analysis of both budget and transport estimates which provide indications for the climate impact of these compounds.

  10. Bioavailability of oxalic acid from spinach, sugar beet fibre and a solution of sodium oxalate consumed by female volunteers.

    PubMed

    Hanson, C F; Frankos, V H; Thompson, W O

    1989-03-01

    Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.

  11. Nutrient absorption.

    PubMed

    Rubin, Deborah C

    2004-03-01

    Our understanding of nutrient absorption continues to grow, from the development of unique animal models and from studies in which cutting-edge molecular and cellular biologic approaches have been used to analyze the structure and function of relevant molecules. Studies of the molecular genetics of inherited disorders have also provided many new insights into these processes. A major advance in lipid absorption has been the cloning and characterization of several intestinal acyl CoA:monoacylglycerol acyltransferases; these may provide new targets for antiobesity drug therapy. Studies of intestinal cholesterol absorption and reverse cholesterol transport have encouraged the development of novel potential treatments for hyperlipidemia. Observations in genetically modified mice and in humans with mutations in glucose transporter 2 suggest the importance of a separate microsomal membrane transport pathway for glucose transport. The study of iron metabolism has advanced greatly with the identification of the hemochromatosis gene and the continued examination of the genetic regulation of iron absorptive pathways. Several human thiamine transporters have been identified, and their specific roles in different tissues are being explored.

  12. The Interaction between Enterobacteriaceae and Calcium Oxalate Deposits

    PubMed Central

    Barr-Beare, Evan; Saxena, Vijay; Hilt, Evann E.; Thomas-White, Krystal; Schober, Megan; Li, Birong; Becknell, Brian; Hains, David S.; Wolfe, Alan J.; Schwaderer, Andrew L.

    2015-01-01

    Background The role of calcium oxalate crystals and deposits in UTI pathogenesis has not been established. The objectives of this study were to identify bacteria present in pediatric urolithiasis and, using in vitro and in vivo models, to determine the relevance of calcium oxalate deposits during experimental pyelonephritis. Methods Pediatric kidney stones and urine were collected and both cultured and sequenced for bacteria. Bacterial adhesion to calcium oxalate was compared. Murine kidney calcium oxalate deposits were induced by intraperitoneal glyoxalate injection and kidneys were transurethrally inoculated with uropathogenic Escherichia coli to induce pyelonephritis Results E. coli of the family Enterobacteriaceae was identified in patients by calcium oxalate stone culture. Additionally Enterobacteriaceae DNA was sequenced from multiple calcium oxalate kidney stones. E. coli selectively aggregated on and around calcium oxalate monohydrate crystals. Mice inoculated with glyoxalate and uropathogenic E. coli had higher bacterial burdens, increased kidney calcium oxalate deposits and an increased kidney innate immune response compared to mice with only calcium oxalate deposits or only pyelonephritis. Conclusions In a murine model, the presence of calcium oxalate deposits increases pyelonephritis risk, likely due to preferential aggregation of bacteria on and around calcium oxalate crystals. When both calcium oxalate deposits and uropathogenic bacteria were present, calcium oxalate deposit number increased along with renal gene transcription of inner stone core matrix proteins increased. Therefore renal calcium oxalate deposits may be a modifiable risk factor for infections of the kidney and urinary tract. Furthermore, bacteria may be present in calcium oxalate deposits and potentially contribute to calcium oxalate renal disease. PMID:26448465

  13. Intestinal Barrier and Behavior.

    PubMed

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses.

  14. Biochemistry of intestinal development.

    PubMed Central

    Henning, S J

    1979-01-01

    In biochemical terms, the rat small intestine is relatively immature at birth and for the first two postnatal weeks. Then during the third week a dramatic array of enzymic changes begins, and by the end of the fourth week the intestine has the digestive and absorptive properties of the adult. Selective examples of these changes are discussed with emphasis on their implications for toxicological studies. The review also includes a detailed consideration of the roles of the dietary change of weaning and of glucocorticoid and thyroid hormones in the regulation of intestinal development. PMID:575507

  15. Oxalate content of foods and its effect on humans.

    PubMed

    Noonan, S C; Savage, G P

    1999-03-01

    Oxalic acid and its salts occur as end products of metabolism in a number of plant tissues. When these plants are eaten they may have an adverse effect because oxalates bind calcium and other minerals. While oxalic acid is a normal end product of mammalian metabolism, the consumption of additional oxalic acid may cause stone formation in the urinary tract when the acid is excreted in the urine. Soaking and cooking of foodstuffs high i