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Sample records for intestinal cholesterol absorption

  1. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

  2. Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice.

    Science.gov (United States)

    Dimova, Lidiya G; de Boer, Jan Freark; Plantinga, Josee; Plösch, Torsten; Hoekstra, Menno; Verkade, Henkjan J; Tietge, Uwe J F

    2017-08-01

    In nematodes, the intestine senses and integrates early life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from maternal milk and investigate the consequences of decreased milk cholesterol availability, early in life, on the metabolism of cholesterol in adult mice. We blocked intestinal absorption of cholesterol in milk fed to newborn mice by supplementing the food of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted into milk. Ezetimibe interacts with the intestinal cholesterol absorption transporter NPC1l1 to block cholesterol uptake into enterocytes. Characterization of these offspring at 24 weeks of age showed a 27% decrease in cholesterol absorption (P intestine. We observed increased histone H3K9me3 methylation at positions -423 to -607 of the proximal Npc1l1 promoter in small intestine tissues from 24-week-old offspring fed ezetimibe during lactation, compared with controls. These findings show that the early postnatal mammalian intestine functions as an environmental sensor of nutritional conditions, responding to conditions such as low cholesterol levels by epigenetic modifications of genes. Further studies are needed to determine how decreased sterol absorption for a defined period might activate epigenetic regulators; the findings of our study might have implications for human infant nutrition and understanding and preventing cardiometabolic disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Developments in intestinal cholesterol transport and triglyceride absorption.

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    Paalvast, Yared; de Boer, Jan Freark; Groen, Albert K

    2017-06-01

    To discuss recent advances in research focused on intestinal lipid handling. An important strategy in reducing atherosclerosis and risk of cardiovascular events is to increase the rate of reverse cholesterol transport, including its final step; cholesterol excretion from the body. The rate of removal is determined by a complex interplay between the factors involved in regulation of intestinal cholesterol absorption. One of these factors is a process known as transintestinal cholesterol excretion. This pathway comprises transport of cholesterol directly from the blood, through the enterocyte, into the intestinal lumen. In humans, this pathway accounts for 35% of cholesterol excretion in the feces. Mechanistic studies in mice revealed that, activation of the bile acid receptor farnesoid X receptor increases cholesterol removal via the transintestinal cholesterol excretion pathway as well as decreases plasma cholesterol and triglyceride providing an interesting target for treatment of dyslipidemia in humans. The physical chemical properties of bile acids are under control of farnesoid X receptor and determine intestinal cholesterol and triglyceride solubilization as well as absorption, providing a direct link between these two important factors in the pathogenesis of cardiovascular disease. Besides bile acids, intestinal phospholipids are important for luminal lipid solubilization. Interestingly, phospholipid remodeling through LPCAT3 was shown to be pivotal for uptake of fatty acids by enterocytes, which may provide a mechanistic handle for therapeutic intervention. The importance of the intestine in control of cholesterol and triglyceride homeostasis is increasingly recognized. Recently, novel factors involved in regulation of cholesterol excretion and intestinal triglyceride and fatty acid uptake have been reported and are discussed in this short review.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  7. Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

    Science.gov (United States)

    Wang, Helen H; Portincasa, Piero; de Bari, Ornella; Liu, Kristina J; Garruti, Gabriella; Neuschwander-Tetri, Brent A; Wang, David Q.-H

    2013-01-01

    Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors, and represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. The primary pathophysiologic event is persistent hepatic hypersecretion of biliary cholesterol, which has both hepatic and small intestinal components. The majority of the environmental factors are probably related to Western-type dietary habits, including excess cholesterol consumption. Laparoscopic cholecystectomy, one of the most commonly performed surgical procedures in the US, is nowadays a major treatment for gallstones. However, it is invasive and can cause surgical complications, and not all patients with symptomatic gallstones are candidates for surgery. The hydrophilic bile acid, ursodeoxycholic acid (UDCA) has been employed as first-line pharmacological therapy in a subgroup of symptomatic patients with small, radiolucent cholesterol gallstones. Long-term administration of UDCA can promote the dissolution of cholesterol gallstones. However, the optimal use of UDCA is not always achieved in clinical practice because of failure to titrate the dose adequately. Therefore, the development of novel, effective, and noninvasive therapies is crucial for reducing the costs of health care associated with gallstones. In this review, we summarize recent progress in investigating the inhibitory effects of ezetimibe and statins on intestinal absorption and hepatic biosynthesis of cholesterol, respectively, for the treatment of gallstones, as well as in elucidating their molecular mechanisms by which combination therapy could prevent this very common liver disease worldwide. PMID:23419155

  8. Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K.

    Science.gov (United States)

    Yamanashi, Yoshihide; Takada, Tappei; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

    2017-04-03

    Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

  9. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

    Science.gov (United States)

    Connor, W E; Lin, D S

    1974-04-01

    The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly

  10. Low dietary cholesterol availability during lactation programs intestinal absorption of cholesterol in adult mice

    NARCIS (Netherlands)

    Dimova, Lidiya G; de Boer, Jan Freark; Plantinga, Josee; Plösch, Torsten; Hoekstra, Menno; Verkade, Henkjan J; Tietge, Uwe J F

    In nematodes, the intestine senses and integrates early-life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from

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

    Science.gov (United States)

    Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    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. PMID:25030663

  12. Dietary Plant Sterol Esters Must Be Hydrolyzed to Reduce Intestinal Cholesterol Absorption in Hamsters.

    Science.gov (United States)

    Carden, Trevor J; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2015-07-01

    Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. The STs and the PEs and SEs were poorly hydrolyzed (1.69-4.12%). In contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r = -0.85; P cholesterol excretion (r = 0.92; P cholesterol-lowering properties of PSE. Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation. © 2015 American Society for Nutrition.

  13. Dietary Plant Sterol Esters Must Be Hydrolyzed to Reduce Intestinal Cholesterol Absorption in Hamsters123

    Science.gov (United States)

    Carden, Trevor J; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2015-01-01

    Background: Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). Objective: This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). Methods: Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. Results: The STs and the PEs and SEs were poorly hydrolyzed (1.69–4.12%). In contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r = −0.85; P cholesterol excretion (r = 0.92; P cholesterol-lowering properties of PSE. Conclusions: Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation. PMID:25972524

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

    Science.gov (United States)

    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, Pabsorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice.

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    Rosanna W S Chung

    Full Text Available Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [(14C]cholesterol and [(3H]sitostanol in male C57BL/6 mice fed a high-fat (HF diet with or without 0.6% wt/wt SM for 18 days; and (ii hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt for 4 weeks. Mice supplemented with SM (0.6% wt/wt had significantly increased fecal lipid and cholesterol output and reduced hepatic [(14C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (-30%. Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (-18%. Total liver lipid (mg/organ was significantly reduced in the SM-supplemented mice (-33% and -40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively, as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet.

  16. Dietary Sphingomyelin Lowers Hepatic Lipid Levels and Inhibits Intestinal Cholesterol Absorption in High-Fat-Fed Mice

    Science.gov (United States)

    Chung, Rosanna W. S.; Kamili, Alvin; Tandy, Sally; Weir, Jacquelyn M.; Gaire, Raj; Wong, Gerard; Meikle, Peter J.; Cohn, Jeffrey S.; Rye, Kerry-Anne

    2013-01-01

    Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM) can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i) the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [14C]cholesterol and [3H]sitostanol in male C57BL/6 mice fed a high-fat (HF) diet with or without 0.6% wt/wt SM for 18 days; and (ii) hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt) for 4 weeks. Mice supplemented with SM (0.6% wt/wt) had significantly increased fecal lipid and cholesterol output and reduced hepatic [14C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (−30%). Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (−18%). Total liver lipid (mg/organ) was significantly reduced in the SM-supplemented mice (−33% and −40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively), as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet. PMID:23409094

  17. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

    Science.gov (United States)

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

    2014-01-01

    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 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. PMID:25261526

  18. Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans[S

    Science.gov (United States)

    Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

    2011-01-01

    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. PMID:21482714

  19. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  20. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  1. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  2. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  3. High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis.

    Science.gov (United States)

    Silbernagel, Günther; Chapman, M John; Genser, Bernd; Kleber, Marcus E; Fauler, Günter; Scharnagl, Hubert; Grammer, Tanja B; Boehm, Bernhard O; Mäkelä, Kari-Matti; Kähönen, Mika; Carmena, Rafael; Rietzschel, Ernst R; Bruckert, Eric; Deanfield, John E; Miettinen, Tatu A; Raitakari, Olli T; Lehtimäki, Terho; März, Winfried

    2013-07-23

    This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD. In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD. High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Boesjes, Marije; Wolters, Henk; Bloks, Vincent W.; Bos, Trijnie; van Dijk, Theo H.; Jurdzinski, Angelika; Boverhof, Renze; Wolters, Justina C.; Kuivenhoven, Jan A.; van Deursen, Jan M.; Oude Elferink, Ronald P. J.; Moschetta, Antonio; Kremoser, Claus; Verkade, Henkjan J.; Kuipers, Folkert; Groen, Albert K.

    2017-01-01

    The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The

  5. Cholesterol absorption inhibitors as a therapeutic option for hypercholesterolaemia.

    Science.gov (United States)

    Burnett, John R; Huff, Murray W

    2006-11-01

    The development of cholesterol-lowering drugs (including a variety of statins, bile acid-binding resins and recently discovered inhibitors of cholesterol absorption) has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined targets for LDL cholesterol concentrations. Combination therapy with drugs that have different or complementary mechanisms of action is often needed to achieve lipid goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to conventional drug treatment and remain at high risk for the development and progression of atherosclerotic cardiovascular disease and alternative approaches are needed. The discovery and development of ezetimibe (a novel, selective and potent cholesterol absorption inhibitor) has advanced the treatment of hypercholesterolaemia. New agents including the phytostanol preparation FM-VP4 and inhibitors of acyl coenzyme A:cholesterol acyltransferase, the apical Na(+)-dependent bile acid transporter and microsomal triglyceride transfer protein may also play a future role in combination therapy. This review focuses on the recent progress in the molecular mechanisms of intestinal cholesterol absorption and transport, and novel therapeutic approaches to inhibit the cholesterol absorption process.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ping Xie

    Full Text Available 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.

  8. Evaluation of deuterated cholesterol and deuterated sitostanol for measurement of cholesterol absorption in humans.

    Science.gov (United States)

    Lütjohann, D; Meese, C O; Crouse, J R; von Bergmann, K

    1993-06-01

    The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using markers labeled with stable isotopes ([2,2,4,4,6-2H5]cholesterol or [25,26,26,26,27,27,27-2H4]cholesterol or [26,26,26,27,27,27-2H6] cholesterol and [5,6,22,23-2H4]sitostanol) quantified by gas-liquid chromatography-selected ion monitoring. Tracing of the isotope distribution of the authentic markers and after their intestinal passage, including the microbiological products (coprostanol and coprostanone) revealed stability of the labels. The new method was evaluated in six monkeys on two occasions by comparison with the original method using radioactively labeled cholesterol and sitosterol. The results obtained by the two different methods were in excellent agreement, and absorption ranged from 49% to 73% (mean 60%) for the stable isotope method and from 51% to 69% (mean 62%) for the radioactive method. The coefficient of variation of cholesterol absorption in animals ranged from 3.9% to 15.1% (mean 7.1%) for stable isotopes and 1.9% to 13.6% (mean 5.7%) for radioactive isotopes. In twelve subjects cholesterol absorption was measured by the new method from total fecal samples frozen immediately and compared to results obtained from small fecal aliquots (approximately 1 g) sent by ordinary mail to the laboratory. A significant correlation of cholesterol absorption between the two different sample handlings was obtained (r = 0.981, P < 0.001). In addition, measurement of cholesterol absorption twice in seven volunteers 2 weeks apart revealed identical results. Thus, the new method is extremely safe and reproducible without radioactive exposure to the subjects and labortory staff and can be used on women of child-bearing age.

  9. The absorption of cholesterol and the sterol balance in the Tarahumara Indians of Mexico fed cholesterol-free and high cholesterol diets.

    Science.gov (United States)

    McMurry, M P; Connor, W E; Lin, D S; Cerqueira, M T; Connor, S L

    1985-06-01

    The Tarahumara Indians of Mexico are habituated to a very low cholesterol, low fat diet and have lifelong low plasma cholesterol concentrations. To study cholesterol metabolism in these unusual people, 8 Tarahumara men were fed sequentially a cholesterol-free diet and then a diet containing 900 mg cholesterol under controlled conditions. The intestinal absorption of cholesterol, fecal steroid excretion and sterol balance were determined. During the high cholesterol diet period, the plasma cholesterol level increased from 113 +/- 8 mg/dl to 147 +/- 11 mg/dl (means +/- SD). Cholesterol biosynthesis decreased from 14.0 +/- 0.7 to 7.1 +/- 1.0 mg/kg/day (means +/- SE). The intestinal absorption of cholesterol was 27.7 +/- 6.7% (means +/- SE) during both dietary periods. Compared to other cultures, Tarahumaras had a reduced ability to absorb dietary cholesterol and higher total sterol turnover primarily because of an increased bile acid output. The total sterol disposition over three weeks of the high cholesterol diet accounted for all the absorbed dietary cholesterol.

  10. Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs : measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques

    NARCIS (Netherlands)

    Stellaard, Frans; Kuipers, Folkert

    Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake.

  11. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-02-10

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Gintonin absorption in intestinal model systems

    Directory of Open Access Journals (Sweden)

    Byung-Hwan Lee

    2018-01-01

    Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.

  13. Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

    International Nuclear Information System (INIS)

    Wilson, M.D.

    1985-01-01

    The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

  14. Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.

    Science.gov (United States)

    McFarlane, Matthew R; Liang, Guosheng; Engelking, Luke J

    2014-01-24

    Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes.

  15. Vitamin D and intestinal calcium absorption.

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Administration of phosphatidylcholine-cholesterol liposomes partially reconstitutes fat absorption in chronically bile-diverted rats

    NARCIS (Netherlands)

    Nishioka, T; Havinga, R; Tazuma, S; Stellaard, F; Kuipers, F; Verkade, HJ

    2004-01-01

    Background and aims: Intestinal bile deficiency in cholestatic patients leads to fat malabsorption. We addressed the potency of model bile, bile salts and phosphatidylcholine (PC)-cholesterol (CH) liposomes to reconstitute fat absorption in permanently bile-diverted (BD) rats. Methods: The plasma

  17. Dietary cholesterol induces trafficking of intestinal Niemann-Pick Type C1 Like 1 from the brush border to endosomes

    DEFF Research Database (Denmark)

    Skov, Marianne; Tønnesen, Carina K; Hansen, Gert H

    2011-01-01

    The transmembrane protein Niemann-Pick C1 Like 1 (NPC1L1) belongs to the Niemann-Pick C1 (NPC1) family of cholesterol transporters and is mainly expressed in the liver and the small intestine. NPC1L1 is believed to be the main transporter responsible for the absorption of dietary cholesterol. Lik...

  18. Fatty acids modulate the expression levels of key proteins for cholesterol absorption in Caco-2 monolayer.

    Science.gov (United States)

    Yang, Fang; Chen, Guoxun; Ma, Meihu; Qiu, Ning; Zhu, Lingjiao; Li, Jing

    2018-02-20

    Fatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. The current study investigates the unknown mechanism by which fatty acids modulate cholesterol absorption. We evaluated the effects of six fatty acids palmitic acid (PAM), oleic acid (OLA), linoleic acid (LNA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cholesterol uptake and transport in human enterocytes Caco-2 cells, and on the mRNA expression levels of NPC1L1, others proteins (ABCG5, ABCG8, ABCA1, ACAT2, MTP, Caveolin 1, Annexin-2) involved in cholesterol absorption, and SREBP-1 and SREBP-2 that are responsible for lipid metabolism. The polyunsaturated fatty acids (PUFAs), especially for EPA and DHA, dose-dependently inhibited cholesterol uptake and transport in Caco-2 monolayer, while saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) had no inhibitory effects. EPA and DHA inhibited cholesterol absorption in Caco-2 monolayer might be caused by down-regulating NPC1L1 mRNA and protein levels, which were associated with inhibition of SREBP-1/- 2 mRNA expression levels. Results from this study indicate that functional food containing high PUFAs may have potential therapeutic benefit to reduce cholesterol absorption. Further studies on this topic may provide approaches to control lipid metabolism and to promote health.

  19. Neural regulation of intestinal nutrient absorption.

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Intestinal absorption of fluorescently labeled nanoparticles.

    Science.gov (United States)

    Simovic, Spomenka; Song, Yunmei; Nann, Thomas; Desai, Tejal A

    2015-07-01

    Characterization of intestinal absorption of nanoparticles is critical in the design of noninvasive anticancer, protein-based, and gene nanoparticle-based therapeutics. Here we demonstrate a general approach for the characterization of the intestinal absorption of nanoparticles and for understanding the mechanisms active in their processing within healthy intestinal cells. It is generally accepted that the cellular processing represents a major drawback of current nanoparticle-based therapeutic systems. In particular, endolysosomal trafficking causes degradation of therapeutic molecules such as proteins, lipids, acid-sensitive anticancer drugs, and genes. To date, investigations into nanoparticle processing within intestinal cells have studied mass transport through Caco-2 cells or everted rat intestinal sac models. We developed an approach to visualize directly the mechanisms of nanoparticle processing within intestinal tissue. These results clearly identify a mechanism by which healthy intestinal cells process nanoparticles and point to the possible use of this approach in the design of noninvasive nanoparticle-based therapies. Advances in nanomedicine have resulted in the development of new therapies for various diseases. Intestinal route of administration remains the easiest and most natural. The authors here designed experiments to explore and characterize the process of nanoparticle transport across the intestinal tissue. In so doing, further insights were gained for future drug design. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Intestinal Absorption of Thyroid Hormone

    NARCIS (Netherlands)

    N. Kelderman-Bolk (Nienke)

    2015-01-01

    textabstractIn this thesis the treatment of hypothyroidism and absorption of T4 is described from a clinical and basic point of view. Put together the thesis gives insight in the factors influencing LT4 absorption and its results have influenced the timing of LT4 intake.

  2. The hypercholesterolemic effect of dietary coconut fat versus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption.

    Science.gov (United States)

    Meijer, G W; Lemmens, A G; Versluis, A; Van Zutphen, L F; Beynen, A C

    1991-05-01

    In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturated versus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fat versus corn oil is not exerted by influencing cholesterol absorption.

  3. The effect of BAY o 2752 on bile acid absorption and cholesterol esterification

    International Nuclear Information System (INIS)

    Harnett, K.M.

    1988-01-01

    BAY o 2752 [N,N-(1,11-undecandiyl)bis(2,3-dihydro-2-methyl-1H-indole-1-carboxamide)] has been demonstrated to inhibit intestinal cholesterol absorption in rats. Studies were carried out on male Wistar rats to determine if this drug alters intestinal bile acid absorption or cholesterol esterification by acyl CoA: cholesterol acyltransferase (ACAT) or cholesterol ester hydrolase (CEH). BAY o 2752 did not affect intestinal absorption of taurocholic acid (TC) from ileal segments perfused in vivo with a tragacanth suspension in phosphate buffer containing NaCl, TC, and 24- 14 C-TC as determined by the excretory rate of radioactivity in bile. BAY o 2752 also did not affect the uptake of TC into ileal everted sacs incubated in stirred, gassed Krebs-Ringer bicarbonate buffer with 1 mM TC, 24- 14 C-TC and 3 H-inulin. BAY o 2752 also did not bind TC; TG, in a filtrate of the above solutions remained at 92-98% of control

  4. Molecular aspects of intestinal calcium absorption.

    Science.gov (United States)

    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

  5. Trust Your Gut: Galvanizing Nutritional Interest in Intestinal Cholesterol Metabolism for Protection Against Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Jiyoung Lee

    2013-01-01

    Full Text Available Recent studies have demonstrated that the intestine is a key target organ for overall health and longevity. Complementing these studies is the discovery of the trans-intestinal cholesterol efflux pathway and the emerging role of the intestine in reverse cholesterol transport. The surfacing dynamics of the regulation of cholesterol metabolism in the intestine provides an attractive platform for intestine-specific nutritional intervention strategies to lower blood cholesterol levels for protection against cardiovascular diseases. Notably, there is mounting evidence that stimulation of pathways associated with calorie restriction may have a large effect on the regulation of cholesterol removal by the intestine. However, intestinal energy metabolism, specifically the idiosyncrasies surrounding intestinal responses to energy deprivation, is poorly understood. The goal of this paper is to review recent insights into cholesterol regulation by the intestine and to discuss the potential for positive regulation of intestine-driven cholesterol removal through the nutritional induction of pathways associated with calorie restriction.

  6. Biotin absorption by distal rat intestine

    International Nuclear Information System (INIS)

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

    1987-01-01

    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

  7. Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes[S

    Science.gov (United States)

    Engelking, Luke J.; McFarlane, Matthew R.; Li, Christina K.; Liang, Guosheng

    2012-01-01

    Enterocyte cholesterol homeostasis reflects aggregated rates of sterol synthesis, efflux, and uptake from plasma and gut lumen. Cholesterol synthesis and LDL uptake are coordinately regulated by sterol regulatory element-binding proteins (SREBP), whereas sterol efflux is regulated by liver X receptors (LXR). How these processes are coordinately regulated in enterocytes, the site of cholesterol absorption, is not well understood. Here, we treat mice with ezetimibe to investigate the effect of blocking cholesterol absorption on intestinal SREBPs, LXRs, and their effectors. Ezetimibe increased nuclear SREBP-2 8-fold. HMG-CoA reductase (HMGR) and LDL receptor (LDLR) mRNA levels increased less than 3-fold, whereas their protein levels increased 30- and 10-fold, respectively. Expression of inducible degrader of LDLR (IDOL), an LXR-regulated gene that degrades LDLRs, was reduced 50% by ezetimibe. Coadministration of ezetimibe with the LXR agonist T0901317 abolished the reduction in IDOL and prevented the increase in LDLR protein. Ezetimibe-stimulated LDLR expression was independent of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. To maintain cholesterol homeostasis in the face of ezetimibe, enterocytes boost LDL uptake by increasing LDLR number, and they boost sterol synthesis by increasing HMGR and other cholesterologenic genes. These studies reveal a hitherto undescribed homeostatic network in enterocytes triggered by blockade of cholesterol absorption. PMID:22523394

  8. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)

  9. Absorption and transport of cholesterol autoxidation derivatives in rabbits

    International Nuclear Information System (INIS)

    Peng, S.K.; Morin, R.J.; Phillips, G.A.; Xia, G.Z.

    1986-01-01

    Spontaneously autoxidized products of cholesterol have been demonstrated to be angiotoxic and possibly atherogenic. This study investigates the absorption and transport of these cholesterol oxidation derivatives (COD's) as compared to cholesterol. 14 C-labeled cholesterol autoxidized by incubation in a 60 0 C water bath for 5 weeks, then suspended in gelatin and given to New Zealand white rabbits by gastric gavage. Rabbits were sacrificed 24 hours after treatment. COD's were separated by thin layer chromatography (TLC) and radioactivities of each COD and cholesterol were measured. Percentages of each COD and cholesterol in the original mixture before administration and in the rabbits' serum after administration are almost identical, suggesting that the rates of absorption of COD's are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each COD separated by TLC in each lipoprotein fraction showed that cholestane-3β,5α,6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were predominantly present in VLDL (3 x serum concentration) and 25-hydroxycholesterol was predominantly in LDL (2.5 x serum concentration). HDL contained only minute amounts of COD's. The increased levels of COD's in VLDL and LDL may contribute to the atherogenicity of these lipoprotein

  10. A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

    Directory of Open Access Journals (Sweden)

    Takahiro Furune

    2014-12-01

    Full Text Available Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, α-cyclodextrin (α-CD is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that α-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of α-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of α-CD on micellar solubility of cholesterol.Results: α-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF, and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and α-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and α-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of α-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated.Conclusion: This study suggests that α-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with α-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by α-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with α-CD addition.

  11. Egg-Yolk Sphingomyelin and Phosphatidylcholine Attenuate Cholesterol Absorption in Caco-2 Cells.

    Science.gov (United States)

    Yang, Fang; Chen, Guoxun; Ma, Meihu; Qiu, Ning; Zhu, Lingjiao; Li, Jing

    2018-02-01

    Phospholipids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is regulated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. The mechanism by which phospholipids modulate cholesterol absorption remains unknown. Here, we evaluate the effects of egg-yolk phospholipids on cholesterol absorption and transport in human colon carcinoma cell line (Caco-2 cells) and on the expression of NPC1L1 and others proteins associated with cholesterol absorption (ABCG5, ABCG8, ABCA1, ACAT2, MTP, CAV-1, ANX-2). The roles of SREBP-1 and SREBP-2 in this process were also investigated. The results show that egg-yolk sphingomyelin (CerPCho) and phosphatidylcholine (PtdCho) inhibit cholesterol transport in the Caco-2 monolayer in a dose-dependent manner. These might be due to the decrease of the cholesterol solubility in micelles as well as to the increases in the micellar sizes and the bile acid-binding capacity. Furthermore, the treatments with egg-yolk CerPCho or PtdCho at 1.2 mmol/L reduced the expression levels of NPC1L1 protein to 21 or 22%, respectively, and its mRNA to 9 or 31% of that in the control group (p egg-yolk PtdCho and CerPCho on the mRNA levels of SREBP-1, and SREBP-2. These results suggest that the inhibitory effect of egg-yolk CerPCho and PtdCho on cholesterol transport might be due to their interference with the physicochemical properties of micelles and their regulations on the expression of the NPC1L1 gene. © 2018 AOCS.

  12. Intestinal absorption of biotin in the rat

    International Nuclear Information System (INIS)

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

    1986-01-01

    We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing [ 3 H]biotin and [ 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

  13. Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression

    Directory of Open Access Journals (Sweden)

    Takuya Kikuchi

    2016-11-01

    Conclusion: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

  14. Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice*

    Science.gov (United States)

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

    2013-01-01

    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. PMID:24019513

  15. In vivo and In vitro Evaluations of Intestinal Gabapentin Absorption

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Frølund, Sidsel; Nøhr, Martha Kampp

    2015-01-01

    PURPOSE: Gabapentin exhibits saturable absorption kinetics, however, it remains unclear which transporters that are involved in the intestinal transport of gabapentin. Thus, the aim of the current study was to explore the mechanistic influence of transporters on the intestinal absorption...... cells. The effect of co-application of the LAT-inhibitor, BCH, and the b(0,+)-substrate, L-lysine, on intestinal transport of gabapentin was evaluated in vivo and in vitro. RESULTS: Gabapentin showed dose-dependent oral absorption kinetics and dose-independent disposition kinetics. Co-application of BCH...... inhibited intestinal absorption in vivo and apical uptake in vitro, whereas no effect was observed following co-application of L-lysine. CONCLUSIONS: The present study shows for the first time that BCH was capable of inhibiting intestinal absorption of gabapentin in vivo. Furthermore, in Caco-2 cell...

  16. Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters.

    Science.gov (United States)

    Ash, Mark M; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2011-07-01

    The dietary impact of specific phytosterols incorporated into phytosterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytosterol esters containing different sterol moieties (sitosterol, sitostanol, or stigmasterol) but the same fatty acid moiety (stearic acid) produce different effects on cholesterol metabolism. Male Syrian hamsters were fed sitosterol, sitostanol, and stigmasterol stearate esters (25 g/kg diet) in an atherogenic diet containing cholesterol (1.2 g/kg) and coconut oil (80 g/kg). The phytosterol stearates produced no decrease in cholesterol absorption or plasma non-high-density lipoprotein cholesterol despite a reduction in liver free cholesterol in hamsters fed both sitosterol and sitostanol stearate diets. In addition, sitosterol stearate significantly increased fecal esterified and total neutral sterol excretion. Stigmasterol stearate did not differ from control in neutral sterol excretion, plasma lipids, or hepatic lipid concentration. Sitosterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmasterol stearate equivalently demonstrated the lowest. The cholesterol-lowering effect in liver-but not plasma-and the limited presence of fecal free sterols indicate that intact (unhydrolyzed) phytosterol stearates may impact cholesterol metabolism by mechanisms unrelated to the role of free phytosterols. The consumption of phytosterol esters at 2.5% of the diet elicited only modest impacts on cholesterol metabolism, although sitosterol stearate had a slightly greater therapeutic impact by lowering liver free cholesterol and increasing esterified and total neutral sterol fecal excretion, possibly due to a greater level of intestinal hydrolysis. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Absorption of l-methionine from the human small intestine

    Science.gov (United States)

    Schedl, Harold P.; Pierce, Charles E.; Rider, Alan; Clifton, James A.

    1968-01-01

    Absorption of L-methionine was measured in all parts of the human small intestine using transintestinal intubation and perfusion. In four normal subjects, adsorption was higher in the proximal than in the distal intestine. In two patients with nontropical sprue in relapse, there was a proximal zone of low absorption with higher absorption distally. In all parts of the small intestine, absorption showed rate-limiting kinetics as methionine concentration was increased. In normal subjects, the proximal Km (Michaelis constant) was more than 3 times higher than the distal, which suggests a difference in transport mechanisms between the two segments. PMID:12066784

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

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    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

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

    International Nuclear Information System (INIS)

    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

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → 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 β 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 [ 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 [ 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-mediated pathway rather

  20. [Study on absorption kinetics of betulic acid in rat's intestines].

    Science.gov (United States)

    Xu, Huijun; Ren, Xiaohua; Du, Yingfeng; Zhang, Lantong; Li, Tao; Ge, Ying; Wang, Huijie

    2012-02-01

    To establish a HPLC-DAD method for determining concentrations of betulic acid and phenol red in intestinal circulation liquid, and probe into the absorption kinetic characteristics of betulic acid at different intestine segments in rats and the effect of different drug concentrations on absorption. The rat intestinal absorption model was established to detect the impact of absorption site, drug concentration and pH value on drug absorption. Within the range from 75-125 mg x L(-1), the absorption rate and the quality concentration of betulic acid had a linear relation, with Ka value keeping unchanged. The absorption rate for each intestinal segment showed no remarkable difference, with Ka values in duodenum, jejunum, ileum and colon being (0.151 +/- 0.0049), (0.159 +/- 0.0056), (0.156 +/- 6.0083), (0.149 +/- 0.0041) h(-1), respectively. Betulic acid is proved to be well absorbed in intestines marked by no specific absorption site in the intestine. The absorption mechanism of the drug conforms to passive transport mechanism and first-order kinetics. The bioavailability of betulic acid preparation can be increased by enhancing the dissolution rate and the solubility.

  1. [Intestinal absorption kinetics of Polygonum capitatum extract in rats].

    Science.gov (United States)

    Yang, Wu; Hou, Jia; Lu, Yuan; Chen, Peng-cheng; Liao, Shang-gao; Huang, Yong

    2015-11-01

    A UPLC-ESI-MS/MS method was used to determinate the main active fractions gallic acid, protocatechuic acid, myricetrin, hyperoside and quercitrin in Polygonum capitatum extracts by in situ intestinal perfusion models; the absorption rate constants and cumulative penetration rate of absorption were calculated. The effect of different drug concentrations, different intestine segments, bile and P-gp inhibitors on the absorption mechanism of Gallic acid and other compositions in P. capitatum extracts. The experimental results showed that gallic acid, protocatechuic acid, myricetrin and quercitrin were observed saturated at high concentration (P absorption and had promotion effect on myricetrin and hyperoside absorption (P absorption of Protocatechuic acid (P absorption of various compositions was that small intestine > colon. This indicated that the absorption mechanism of P. capitatum extracts in rat intestine was in line with fist-order kinetics characteristics. The composition could be absorbed in all of the different intestinal segments, and the absorption was mainly concentrated in small intestine. The protocatechuic acid may be the substrate of P-gp.

  2. Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, K.R.; Moser, A.H.

    1987-11-01

    Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo(3,4-d)pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of /sup 3/H/sub 2/O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats.

  3. Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

    International Nuclear Information System (INIS)

    Feingold, K.R.; Moser, A.H.

    1987-01-01

    Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo[3,4-d]pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of 3 H 2 O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats

  4. Evaluation of cholesterol absorption and biosynthesis by decoctions of Annona cherimola leaves.

    Science.gov (United States)

    Falé, Pedro L; Ferreira, Catarina; Maruzzella, Federica; Helena Florêncio, Maria; Frazão, Fátima N; Serralheiro, Maria L M

    2013-11-25

    Decoctions of the leaves of Annona cherimola Mill. are traditionally used in Azores to treat hypercholesterolemia. Although they are sold and consumed by people in order to improve their health, these are products that cannot be sold with claims for health benefits as they have never been studied scientifically. The activities of decoctions from Annona cherimola leaves were analysed for the two therapeutic approaches currently used to reduce plasma cholesterol: inhibition of dietary cholesterol uptake and inhibition of HMG-CoA reductase activity. Furthermore, the composition of the decoction was elucidated by LC-MS and the permeability of the active components was analysed using Caco-2 cell monolayers as a model of the intestinal barrier (dietary cholesterol uptake). The chemical composition of the Annona cherimola leaves' extract revealed that rutin was its main component. The in vitro gastrointestinal digestion did not modify the chemical composition of the extract. This extract was able to originate a slight reduction in cholesterol absorption through Caco-2 cells lines and to reduce the HMG-CoA reductase activity in 50% when using 137.3 μg of the extract/mL. Rutin, when used in the same concentration as that found in the extract, was able to reduce cholesterol absorption through Caco-2 cells monolayer in approximately 47%. This flavonoid had an IC50 of 17.85 μM relatively to the HMG-CoA reductase activity. The traditional use of decoctions from the leaves of Annona cherimola may be justified, at least by the inhibition of HMG-CoA reductase activity. © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase.

    Science.gov (United States)

    Brun, Lucas R; Brance, María L; Lombarte, Mercedes; Lupo, Maela; Di Loreto, Verónica E; Rigalli, Alfredo

    2014-07-01

    Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Quantitation of small intestinal permeability during normal human drug absorption

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  7. Absorption sites of orally administered drugs in the small intestine.

    Science.gov (United States)

    Murakami, Teruo

    2017-12-01

    In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

  8. Intestinal permeability and carrier-mediated monosaccharide absorption in preterm neonates during the early postnatal period

    NARCIS (Netherlands)

    Rouwet, Ellen V.; Heineman, Erik; Buurman, Wim A.; ter Riet, Gerben; Ramsay, Graham; Blanco, Carlos E.

    2002-01-01

    Immaturity of intestinal epithelial barrier function and absorptive capacity may play a role in the pathophysiology of intestinal complications in preterm neonates during the early postnatal period. We determined the intestinal permeability and carrier-mediated absorption of monosaccharides in

  9. Biopharmaceutics classification and intestinal absorption study of apigenin.

    Science.gov (United States)

    Zhang, Jianjun; Liu, Dapeng; Huang, Yanting; Gao, Yuan; Qian, Shuai

    2012-10-15

    The aim of the study was to characterize the biopharmaceutics classification system (BCS) category of apigenin (AP) using intrinsic dissolution rate (IDR) and rat intestinal permeability, and to investigate the intestinal absorption mechanism of AP in rats. In the present investigation, equilibrium solubility and intrinsic dissolution rate (IDR) of AP were estimated in phosphate buffers. Effective intestinal permeability (P(eff)) of AP was determined using single-pass intestinal perfusion (SPIP) technique in four segments (duodenum, jejunum, ileum and colon) of rat intestine at three concentrations (10, 50 and 100 μg/ml). The aqueous solubility of AP in tested phosphate buffers was very poor with maximum solubility of 2.16 μg/ml at pH 7.5. The IDR of AP was very low with a value of 0.006 mg/min/cm(2). The minimum and maximum P(eff)s determined by SPIP were 0.198×10(-4) and 0.713×10(-4) cm/s at jejunum and duodenum site, respectively. In addition, the concentration-dependent permeability behavior was observed in the duodenum and jejunum, which suggested that AP was transported by both passive and active carrier-mediated saturable mechanism in these two intestinal segments. However, the observed concentration-independent permeability behavior in ileum and colon indicated primarily passive transport mechanism of absorption of AP in the last two intestinal segments. AP was classified as class II drug of the BCS due to its low solubility and high intestinal permeability. AP could be well absorbed in the whole intestine with the main absorption site at duodenum. The absorption of AP in four intestinal segments exhibited different transport mechanisms. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Validation of a dual-isotope plasma ratio method for measurement of cholesterol absorption in rats.

    Science.gov (United States)

    Zilversmit, D B; Hughes, L B

    1974-09-01

    Several methods for measuring cholesterol absorption in the rat have been compared. After administration of an oral dose of labeled cholesterol ((14)C or (3)H) and an intravenous dose of colloidal labeled cholesterol ((3)H or (14)C) the ratio of the two labels in plasma or whole blood 48 hr or more after dosing compared closely to the ratio of areas under the respective specific activity-time curves. The area ratio method is independent of a time lag between the appearance of oral and intravenous label in the bloodstream. Both measures of cholesterol absorption agree fairly well with a method based on measuring the unabsorbed dietary cholesterol in a pooled fecal sample. The plasma isotope ratio method gave more reproducible results than the fecal collection method when the measurement was repeated in the same animals 5 days after the first measurement. Cholesterol absorption was overestimated by the use of Tween 20-solubilized labeled cholesterol for the intravenous dose. The plasma disappearance curves of injected labeled colloidal cholesterol and cholesterol-labeled chylomicrons infused intravenously over a 3.5-hr period in the same animal coincided within experimental error from the first day until 75 days after injection. The plasma isotope ratio method for cholesterol absorption gave the same results in rats practicing coprophagy as in those in which this practice was prevented. The addition of sulfaguanidine to the diet lowered cholesterol absorption as measured by the plasma isotope ratio to the same degree as that measured by the fecal collection method.

  11. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  12. Quantitation of the rates of hepatic and intestinal cholesterol synthesis in lysosomal acid lipase-deficient mice before and during treatment with ezetimibe.

    Science.gov (United States)

    Chuang, Jen-Chieh; Lopez, Adam M; Turley, Stephen D

    2017-07-01

    Esterified cholesterol (EC) and triglycerides, contained within lipoproteins taken up by cells, are hydrolysed by lysosomal acid lipase (LAL) in the late endosomal/lysosomal (E/L) compartment. The resulting unesterified cholesterol (UC) is transported via Niemann-Pick type C2 and C1 into the cytosolic compartment where it enters a putative pool of metabolically active cholesterol that is utilized in accordance with cellular needs. Loss-of-function mutations in LIPA, the gene encoding LAL, result in dramatic increases in tissue concentrations of EC, a hallmark feature of Wolman disease and cholesteryl ester storage disease (CESD). The lysosomal sequestration of EC causes cells to respond to a perceived deficit of sterol by increasing their rate of cholesterol synthesis, particularly in the liver. A similar compensatory response occurs with treatments that disrupt the enterohepatic movement of cholesterol or bile acids. Here we measured rates of cholesterol synthesis in vivo in the liver and small intestine of a mouse model for CESD given the cholesterol absorption inhibitor ezetimibe from weaning until early adulthood. Consistent with previous findings, this treatment significantly reduced the amount of EC sequestered in the liver (from 132.43±7.35 to 70.07±6.04mg/organ) and small intestine (from 2.78±0.21 to 1.34±0.09mg/organ) in the LAL-deficient mice even though their rates of hepatic and intestinal cholesterol synthesis were either comparable to, or exceeded those in matching untreated Lal -/- mice. These data reveal the role of intestinal cholesterol absorption in driving the expansion of tissue EC content and disease progression in LAL deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Plasma plant sterols serve as poor markers of cholesterol absorption in man

    NARCIS (Netherlands)

    Jakulj, Lily; Mohammed, Hussein; van Dijk, Theo H.; Boer, Theo; Turner, Scott; Groen, Albert K.; Vissers, Maud N.; Stroes, Erik S. G.

    The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail. Nevertheless, plant sterol concentrations are routinely used to describe treatment-induced changes in cholesterol absorption. Their use has also been advocated as a clinical tool to tailor

  14. Effect of zinc supplements on the intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Spencer, H.; Rubio, N.; Kramer, L.; Norris, C.; Osis, D.

    1987-01-01

    Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca-47 and determining plasma levels and urinary and fecal excretions of Ca-47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake

  15. PXR induces CYP27A1 and regulates cholesterol metabolism in the intestine.

    Science.gov (United States)

    Li, Tiangang; Chen, Wenling; Chiang, John Y L

    2007-02-01

    Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyzes oxidative cleavage of the sterol side chain in the bile acid biosynthetic pathway in the liver and 27-hydroxylation of cholesterol in most tissues. Recent studies suggest that 27-hydroxycholesterol (27-HOC) activates liver orphan receptor alpha (LXRalpha) and induces the cholesterol efflux transporters ABCA1 and ABCG1 in macrophages. The steroid- and bile acid-activated pregnane X receptor (PXR) plays critical roles in the detoxification of bile acids, cholesterol metabolites, and xenobiotics. The role of CYP27A1 in the intestine is not known. This study investigated PXR and CYP27A1 regulation of cholesterol metabolism in the human intestinal cell lines Caco2 and Ls174T. A human PXR ligand, rifampicin, induced CYP27A1 mRNA expression in intestine cells but not in liver cells. Rifampicin induced CYP27A1 gene transcription, increased intracellular 27-HOC levels, and induced ABCA1 and ABCG1 mRNA expression only in intestine cells. A functional PXR binding site was identified in the human CYP27A1 gene. Chromatin immunoprecipitation assays revealed that rifampicin induced the PXR recruitment of steroid receptor coactivator 1 to CYP27A1 chromatin. Cholesterol loading markedly increased intracellular 27-HOC levels in intestine cells. Rifampicin, 27-HOC, and a potent LXRalpha agonist, T0901317, induced ABCA1 and ABCG1 protein expression and stimulated cholesterol efflux from intestine cells to apolipoprotein A-I and HDL. This study suggests an intestine-specific PXR/CYP27A1/LXRalpha pathway that regulates intestine cholesterol efflux and HDL assembly.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 ( 3 H)-biotin and ( 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 μM 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

  17. Intestinal absorption of specific structured triacylglycerols

    DEFF Research Database (Denmark)

    Mu, Huiling; Høy, Carl-Erik

    2001-01-01

    -sn-glycerol (10:0/18:2/10:0), and 1,3-didodecanoyl-2-linoleoyl-sn-glycerol (12:0/18:2/12:0) in a rat model. Safflower oil was used in the absorption study in order to compare the absorption of medium- chain fatty acids and long-chain fatty acids, The triacylglycerol species of lymph Lipids were separated......-type triacylglycerols. From the present study we conclude that the medium-chain fatty acids from STAG, in addition to absorption into the portal blood as free fatty acids, are absorbed by the same pathway as the conventional long-chain triacylglycerols, that is, they are hydrolyzed into free fatty acids, absorbed...

  18. Glutamine protects intestinal calcium absorption against oxidative stress and apoptosis.

    Science.gov (United States)

    Moine, Luciana; Díaz de Barboza, Gabriela; Pérez, Adriana; Benedetto, Mercedes; Tolosa de Talamoni, Nori

    2017-10-01

    The aim of this study was to investigate whether glutamine (GLN) could block the inhibition of the intestinal Ca 2+ absorption caused by menadione (MEN), and elucidate the underlying mechanisms. To do this, one-month old chicks were divided in four groups: 1) controls, 2) MEN treated, 3) GLN treated and 4) GLN treated before or after MEN treatment. Intestinal Ca 2+ absorption as well as protein expression of molecules involved in the transcellular Ca 2+ pathway were determined. Glutathione (GSH) and superoxide anion and activity of enzymes of the antioxidant system were evaluated. Apoptosis was measured by the TUNEL technique, the expression of FAS and FASL and the caspase-3 activity. A previous dose of 0.5gGLN/kg of b.w. was necessary to show its protector effect and a dose of 1g/kg of b.w. could restore the intestinal Ca 2+ absorption after MEN treatment. GLN alone did not modify the protein expression of calbindin D 28k and plasma membrane Ca 2+ -ATPase, but blocked the inhibitory effect of the quinone. GLN avoided changes in the intestinal redox state provoked by MEN such as a decrease in the GSH content, and increases in the superoxide anion and in the SOD and CAT activities. GLN abrogated apoptotic effects caused by MEN in intestinal mucosa, as indicated by the reduction of TUNEL (+) cells and the FAS/FASL/caspase-3 pathway. In conclusion, GLN could be an oral nutritional supplement to normalize the redox state and the proliferation/cell death ratio in the small intestine improving the intestinal Ca 2+ absorption altered by oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Hydroxycitric acid delays intestinal glucose absorption in rats

    NARCIS (Netherlands)

    Wielinga, PY; Wachters-Hagedoorn, RE; Bouter, B; van Dijk, TH; Stellaard, F; Nieuwenhuizen, AG; Verkade, HJ; Scheurink, AJW; Nieuwenhuizen, Arie G.; Verkade, Henkjan J.

    In this study, we investigated in rats if hydroxycitric acid (HCA) reduces the postprandial glucose response by affecting gastric emptying or intestinal glucose absorption. We compared the effect of regulator HCA (310 mg/kg) and vehicle (control) on the glucose response after an intragastric or

  20. The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies.

    Science.gov (United States)

    Stellaard, Frans; von Bergmann, Klaus; Sudhop, Thomas; Lütjohann, Dieter

    2017-05-01

    Regulation of cholesterol (Chol) homeostasis is controlled by three main fluxes, i.e. intestinal absorption, de novo synthesis (ChS) and catabolism, predominantly as bile acid synthesis (BAS). High serum total Chol and LDL-Chol concentrations in particular are considered risk factors and markers for the development of atherosclerosis. Pharmaceutical treatments to lower serum Chol have focused on reducing absorption or ChS and increasing BAS. Monitoring of these three parameters is complex involving isotope techniques, cholesterol balance experiments and advanced mass spectrometry based analysis methods. Surrogate markers were explored that require only one single fasting blood sample collection. These markers were validated in specific, mostly physiological conditions and during statin treatment to inhibit ChS. They were also applied under cholesterol absorption restriction, but were not validated in this condition. We retrospectively evaluated the use of serum campesterol (Camp), sitosterol (Sit) and cholestanol (Cholol) as markers for cholesterol absorption, lathosterol (Lath) as marker for ChS and 7α-hydroxycholesterol (7α-OH-Ch) and 27-hydroxycholesterol (27-OH-Ch) as markers for BAS under conditions of Chol absorption restriction. Additionally, their values were corrected for Chol concentration (R_sterol or oxysterols). Thirty-seven healthy male omnivore subjects were studied under treatments with placebo (PLAC), ezetimibe (EZE) to inhibit cholesterol absorption, simvastatin (SIMVA) to reduce cholesterol synthesis and a combination of both (EZE+SIMVA). Results were compared to those obtained in 18 pure vegetarian subjects (vegans) whose dietary Chol intake is extremely low. Relative or fractional Chol absorption (FrChA) was measured with the continuous feeding stable isotope procedure, ChS and BAS with the cholesterol balance method. The daily Chol intake (DICh) was inventoried and the daily Chol absorption (DACh) calculated. Monitoring cholesterol

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Optimizing the effect of plant sterols on cholesterol absorption in man.

    Science.gov (United States)

    Mattson, F H; Grundy, S M; Crouse, J R

    1982-04-01

    During three experimental periods, nine adults were hospitalized on a metabolic ward and fed a meal containing 500 mg of cholesterol as a component of scrambled eggs. In addition, the meal contained: 1) no additive, 2) 1 g beta-sitosterol, or 3) 2 g beta-sitosteryl oleate. Stools for the succeeding 5 days were analyzed to determine the percentage of the cholesterol in the test meal that was absorbed. The addition of beta-sitosterol resulted in a 42% decrease in cholesterol absorption; the beta-sitosteryl oleate caused a 33% reduction. These results indicate that the judicious addition of beta-sitosterol or beta-sitosteryl oleate to meals containing cholesterol-rich foods will result in a significant decrease in cholesterol absorption, with a consequent decrease in plasma cholesterol.

  3. Molecular characterisation of non-absorptive and absorptive enterocytes in human small intestine

    DEFF Research Database (Denmark)

    Gassler, N; Newrzella, D; Böhm, C

    2006-01-01

    BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS...... genes, and vesicle/transport related genes was found. CONCLUSION: Two types of enterocytes were dissected at the molecular level, the non-absorptive enterocyte located in the upper part of crypts and the absorptive enterocyte found in the middle of villi. These data improve our knowledge about...... the physiology of the crypt-villus architecture in human small intestine and provide new insights into pathophysiological phenomena, such as villus atrophy, which is clinically important....

  4. Validation of a dual-isotope plasma ratio method for measurement of cholesterol absorption in rats

    International Nuclear Information System (INIS)

    Zilversmit, D.B.; Hughes, L.B.

    1974-01-01

    Several methods for measuring cholesterol absorption in the rat have been compared. After administration of an oral dose of labeled cholesterol ( 14 C or 3 H) and an intravenous dose of colloidal labeled cholesterol ( 3 H or 14 C) the ratio of the two labels in plasma or whole blood 48 hr or more after dosing compared closely to the ratio of areas under the respective specific activity-time curves. The area ratio method is independent of a time lag between the appearance of oral and intravenous label in the bloodstream. Both measures of cholesterol absorption agree fairly well with a method based on measuring the unabsorbed dietary cholesterol in a pooled fecal sample. The plasma isotope ratio method gave more reproducible results than the fecal collection method when the measurement was repeated in the same animals 5 days after the first measurement. Cholesterol absorption was overestimated by the use of Tween 20-solubilized labeled cholesterol for the intravenous dose. The plasma disappearance curves of injected labeled colloidal cholesterol and cholesterol-labeled chylomicrons infused intravenously over a 3.5-h period in the same animal coincided within experimental error from the first day until 75 days after injection. The plasma isotope ratio method for cholesterol absorption gave the same results in rats practicing coprophagy as in those in which this practice was prevented. The addition of sulfaguanidine to the diet lowered cholesterol absorption as measured by the plasma isotope ratio to the same degree as that measured by the fecal collection method. (U.S.)

  5. Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man.

    Science.gov (United States)

    Samuel, P; McNamara, D J; Ahrens, E H; Crouse, J R; Parker, T

    1982-03-01

    Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P., J. R. Crouse, and E. H. Ahrens, Jr. 1978 J. Lipid Res. 19: 82-93). This comparison has now been extended to additional studies carried out in eight hospitalized patients (19 experiments). Of the 34 comparisons between the IRM and the FRM in our hands, 29 were technically acceptable (chromic oxide fecal recovery >/=80%): percent cholesterol absorption was 43.1 +/- 12% by the FRM and 46.0 +/- 11% by the IRM, exhibiting an accuracy within 3.5% at the 95% and 4.7% at the 99% confidence levels. In addition, various procedural modifications of the IRM were studied in out-patients. The measurement of isotope ratios in a single blood sample (analyzed in sextuplicate) on the third day (or later) following the tests gave identical results to those obtained from six to eight daily blood samplings. Blood samples drawn at any time during the day gave cholesterol absorption values similar to those obtained from samples drawn following an overnight fast. Absorption tests carried out before and 1 hr after breakfast, lunch, or dinner, or giving the oral isotope in three divided daily doses all yielded identical results with tests carried out in the am in the fasting state. Cholesterol absorption was markedly reduced when the oral radiolabeled cholesterol was administered in orange juice vs. liquid formula, milk or a solution of glucose and amino acids, consistent with the well-known fact that gallbladder contraction is a critical requirement of cholesterol absorption. A meal high in cholesterol consumed on the day of the test did not influence the results of the absorption measurements. Furthermore, addition of three eggs per day (~750mg cholesterol) for 3 weeks to a

  6. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.

    Science.gov (United States)

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out

  7. Quantitation of small intestinal permeability during normal human drug absorption

    Science.gov (United States)

    2013-01-01

    Background Understanding the quantitative relationship between a drug’s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (“Averaged Model” (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4 cm/sec) corresponding to an unstirred layer of only 45 μm. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH 7.4, suggesting

  8. DIETARY-CHOLESTEROL INDUCED DOWN-REGULATION OF INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IS DIMINISHED IN RABBITS WITH HYPERRESPONSE OF SERUM-CHOLESTEROL TO DIETARY-CHOLESTEROL

    NARCIS (Netherlands)

    MEIJER, GW; SMIT, MJ; VANDERPALEN, JGP; KUIPERS, F; VONK, RJ; VANZUTPHEN, BFM; BEYNEN, AC

    Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was

  9. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters.

    Science.gov (United States)

    Lin, Yuguang; Vermeer, Mario A; Trautwein, Elke A

    2011-01-01

    Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

  10. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

    Directory of Open Access Journals (Sweden)

    Yuguang Lin

    2011-01-01

    Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

  11. Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels.

    Science.gov (United States)

    Otis, Jessica P; Shen, Meng-Chieh; Quinlivan, Vanessa; Anderson, Jennifer L; Farber, Steven A

    2017-03-01

    Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated. In this study the cellular dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic contributions of CAV1 were determined with mice lacking CAV1 in intestinal epithelial cells (CAV1 IEC-KO ). Live imaging of Cav1-GFP and fluorescently labeled caveolae cargos shows localization to the basolateral and lateral enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between enterocytes and the submucosa. CAV1 IEC-KO mice are protected from the elevation in circulating fasted low-density lipoprotein (LDL) cholesterol associated with a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in circulating FAs in HFD CAV1 IEC-KO mice is mirrored by decreased hepatic FAs, suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL cholesterol and several FA species via the basolateral PM of enterocytes. These results point to intestinal epithelial cell CAV1 as a potential therapeutic target to lower circulating FFAs and LDL cholesterol, as high levels are associated with development of type II diabetes and cardiovascular disease. © 2017. Published by The Company of Biologists Ltd.

  12. Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

    Science.gov (United States)

    Wang, Y.-H.; Ke, X.-M.; Zhang, C.-H.; Yang, R.-P.

    2017-01-01

    This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism. PMID:28953988

  13. Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

    Directory of Open Access Journals (Sweden)

    Y.-H. Wang

    2017-09-01

    Full Text Available This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

  14. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    Vyas, M.

    1962-01-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4- 14 C- cholesterol subcutaneously or orally, or the 1- 14 C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [fr

  15. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    Science.gov (United States)

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  16. Studies on intestinal copper and zinc absorption in the rat

    International Nuclear Information System (INIS)

    Oestreicher, P.

    1985-01-01

    An attempt is made to examine the interactions zinc and copper undergo at the absorptive level in the rat. In addition, the kinetics of zinc transport by rat intestinal basolateral membrane vesicles are described. The influence copper and zinc exert on each other's absorption was studied using the isolated, vascularly and luminally perfused rat intestine system. Rats were fed one of nine diets for one week, each with a different copper and zinc concentration representing low, adequate and high dietary concentrations (1-36 mg/kg Cu 2+ and 5-180 mg/kg Zn 2+ ). Experiments to describe zinc transport out of intestinal cells were carried out using a membrane fraction enriched with basolateral membrane vesicles (BLMV). Initial rates of 65 Zn 2+ uptake (extravesicular Zn 2+ concentrations of 5 μM to 625 μM) with BLMV from zinc-adequate and zinc-deficient rats fit Michaelis-Menten saturation kinetics indicating a carrier-mediated transport process. The Km and Jmax were not significantly changed by dietary zinc status. SDS-PAGE of BLMV from rats of different zinc status did not show differences in the number of abundance of protein bands. Na + did not alter 65 Zn 2+ uptake. ATP caused a reduction in 65 Zn 2+ uptake due to complex formation with zinc ions thereby decreasing the amount of zinc available for transport

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

    Science.gov (United States)

    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.

  18. [Study on absorption ingredients of yuanhuzhitong pill by everted intestinal sac method].

    Science.gov (United States)

    Chen, Xiaomeng; Zhang, Yingchun; Lin, Shuo; Yang, Hongjun; Wu, Hongwei; Li, Shaojing; Li, Defeng; Xu, Haiyu

    2012-07-01

    To establish an everted intestinal sac method for determining absorption ingredients of yuanhuzhitong pill and study absorption characteristics of major chemical constituents of yuanhuzhitong pill. The everted intestinal sac model was adopted. Intestinal sac fluid samples at different time points after administration of three concentrations of Yuanhuzhitong pill were collected and determined by HPLC. The accumulative absorbed doses of active constituents were calculated, while the proportion between samples of yuanhuzhitong pill and absorption ingredients was compared. Eight ingredients of Yuanhuzhitong pill can be detected in intestinal sac, they are protopine, palmatine, coptisine, imperatorin, berberine, byakangelicin, alpha-allocryptopine and tetrahydropalmatine. The absorption rate constants (Ka) of eight constituents increased in jejunum and ileum with the increase in concentration of Yuanhuzhitong pill extracts (P absorption. As ingredients are selectively absorbed in intestinal sac, the everted intestinal sac method is selected to assess the intestinal absorption characteristics of ingredients of Yuanhuzhitong prescription.

  19. Absence of intestinal microbiota increases ß-cyclodextrin stimulated reverse cholesterol transport.

    Science.gov (United States)

    Mistry, Rima H; Verkade, Henkjan J; Tietge, Uwe J F

    2017-05-01

    Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria. In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p < 0.05), largely within HDL, while fecal neutral sterol excretion increased (3-fold, p < 0.01) and fecal bile acid excretion was unchanged. Hepatic cholesterol levels and biliary cholesterol secretion were unaltered. Changes in cholesterol metabolism translated into increased macrophage-to-feces RCT in ßCD-administered mice (1.5-fold, p < 0.05). In germ-free C57BL/6J mice ßCD similarly lowered plasma cholesterol (-40%, p < 0.05). However, ßCD increased fecal neutral sterol excretion (7.5-fold, p < 0.01), bile acid excretion (2-fold, p < 0.05) and RCT (2.5-fold, p < 0.01) even more substantially in germ-free mice compared with the effect in conventional mice. In summary, this study demonstrates that ßCD lowers plasma cholesterol levels and increases fecal cholesterol excretion from a RCT-relevant pool. Intestinal bacteria decrease the impact of ßCD on RCT. These data suggest that dietary ßCD might have cardiovascular health benefits. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte; Immerdal, Lissi

    2007-01-01

    Absorption of dietary fat in the small intestine is accompanied by a rise of intestinal alkaline phosphatase (IAP) in the serum and of secretion of IAP-containing surfactant-like particles from the enterocytes. In the present work, fat absorption was studied in organ cultured mouse intestinal exp...

  1. Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

    Directory of Open Access Journals (Sweden)

    Ekin Bolukbasi

    2017-10-01

    Full Text Available Reduced activity of nutrient-sensing signaling networks can extend organismal lifespan, yet the underlying biology remains unclear. We show that the anti-aging effects of rapamycin and reduced intestinal insulin/insulin growth factor (IGF signaling (IIS require the Drosophila FoxA transcription factor homolog Fork Head (FKH. Intestinal FKH induction extends lifespan, highlighting a role for the gut. FKH binds to and is phosphorylated by AKT and Target of Rapamycin. Gut-specific FKH upregulation improves gut barrier function in aged flies. Additionally, it increases the expression of nutrient transporters, as does lowered IIS. Evolutionary conservation of this effect of lowered IIS is suggested by the upregulation of related nutrient transporters in insulin receptor substrate 1 knockout mouse intestine. Our study highlights a critical role played by FKH in the gut in mediating anti-aging effects of reduced IIS. Malnutrition caused by poor intestinal absorption is a major problem in the elderly, and a better understanding of the mechanisms involved will have important therapeutic implications for human aging.

  2. [Design and analyze mathematical algorithms of intestinal absorption and metabolism of multicomponent drug].

    Science.gov (United States)

    Dong, Ling; Xiang, Jia-Mei; Wang, Yun; Wu, Rui-Guang; Tang, Ming-Min; Sun, Mo-Han

    2014-12-01

    Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.

  3. EFFECT OF HIGH FAT DIETS ON INTESTINAL MICROFLORA AND SERUM CHOLESTEROL IN RATS.

    Science.gov (United States)

    GRABER, C D; O'NEAL, R M; RABIN, E R

    1965-01-01

    Graber, C. D. (Baylor University College of Medicine, Houston, Tex.), R. M. O'Neal, and E. R. Rabin. Effect of high fat diets on intestinal microflora and serum cholesterol in rats. J. Bacteriol. 89:47-51. 1965.-Differential bacterial counts of feces and total plasma cholesterol determinations were performed on 60 Wistar rats fed several high lipid diets for a period of approximately 6 months. Fecal flora remained relatively stable irrespective of diet, but cholesterol levels rose in animals fed butter and sodium cholate. The six most commonly cultured organisms in all diets were enterococci, Proteus, lactobacilli, Escherichia coli, Staphylococcus aureus, and other micrococci. No enteric pathogens which did not ferment lactose or fermented it slowly were grown. Fungi and yeasts were rare. Aerobes generally outnumbered anaerobes in proportions which were sometimes as high as 300:1. Clostridium perfringens isolations were consistently high in animals given the butter diets, particularly when sodium cholate was added. Evidence is reviewed which indicates that this organism may play a role in bile salt and cholesterol metabolism. This experiment would seem to demonstrate that differences in plasma-cholesterol levels among the various dietary groups of rats were the result of dietary factors rather than alteration in intestinal flora.

  4. Comparison of two approaches of intestinal absorption by puerarin.

    Science.gov (United States)

    Li, Hewei; Dong, Ling; Liu, Yang; Wang, Gang; Zhang, Lei; Qiao, Yanjiang

    2014-01-01

    Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix. In the present study, three rat models of ex vivo and in situ, EGS, SPIP, and in situ intestinal perfusion with venous sampling (IPVS), were established to determine the permeability coefficient of puerarin. The apparent permeability coefficient (Papp) was obtained by EGS. The SPIP model was used to determine the effective permeability coefficient (Peff) in different intestinal segments. The blood permeability coefficient (Pblood) was determined by IPVS. Puerarin concentration of perfusion and blood samples were measured by HPLC. Puerarin could filter into EGS incubated in aqueous extract of Puerariae Radix or puerarin solution. In the SPIP experiment, the concentration effect on Peff was observed in the ileum, but not in the other three intestinal segments. The Pblood was 0.068±0.002×10(-5)cm/s and was 16-fold lower than the Peff (1.114±0.153×10(-5)cm/s) in the IPVS experiment at 80μg/mL puerarin. As expected, the Peff (1.24±0.11×10(-5)cm/s) in SPIP did not differ from the Peff in IPVS. The Papp was 0.199×10(-5)cm/s at 1200μg/mL puerarin, 10-fold lower than Peff (2.047±0.116×10(-5)cm/s) in SPIP. Three models for permeability were successfully practiced in the study of puerarin absorption and our research strategy will be useful for herbal constituent absorption in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Studies on the intestinal absorption of vitamin B2

    International Nuclear Information System (INIS)

    Yamaguchi, Keiko; Moriwaki, Chiaki

    1978-01-01

    The intestinal absorption of vitamin B 2 was studied by in situ mesenteric perfusion system. Free form riboflavin (FR), FMN and FAD (1 mg each) were injected into the ligated jejunum of rat which was infused Krebs Ringer bicarbonate solution from the superior mesenteric artery. Perfusate was recovered from the mesenteric vein and the recoveries of the total riboflavin during 120 min after the administration of these 3 types vitamin B 2 were 1.0, 1.5 and 2.8%, respectively. Furthermore, riboflavin and its esters were detected in the perfusates from 14 C-FR and 14 C-FAD given rats. There was a considerable amount of labeled substance which was not vitamin B 2 derivatives in the radiopaperchromatogram of the perfusate of 14 C-FR dosed rats, and it is suggested that a portion of riboflavin is decomposed in the process of absorption. (auth.)

  6. Mechanistic and regulatory aspects of intestinal iron absorption

    Science.gov (United States)

    Gulec, Sukru; Anderson, Gregory J.

    2014-01-01

    Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands. PMID:24994858

  7. Intestinal absorption of chromium as affected by wheat bran

    International Nuclear Information System (INIS)

    Keim, K.S.; Holloway, C.L.; Hegsted, M.

    1986-01-01

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100μCi of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium

  8. Computational approaches for modeling human intestinal absorption and permeability.

    Science.gov (United States)

    Subramanian, Govindan; Kitchen, Douglas B

    2006-07-01

    Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2015, American Association for the Advancement of Science.

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

    Science.gov (United States)

    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.

  12. [Study on intestinal absorption of ingredients from different compatibilities of Shaoyao Gancao decoction].

    Science.gov (United States)

    Ma, Ting-ting; He, Rui; Gong, Mu-xin; Xu, Yong-song; Li, Jing; Zhai, Yong-song; Wan, Guang

    2015-11-01

    To study the compatible mechanisms and compatible proportion of Shaoyao Gancao decoction, the intestinal absorption of main ingredients in Shaoyao Gancao decoction SG11 (Baishao-Zhigancao 1: 1) , SG31 (Baishao-Zhigancao 3: 1), Baishao water decoction S and Zhigancao (G) were investigated and compared using in vitro everted intestinal sac model and in situ single pass intestinal perfusion (SPIP) model. The concentration of paeoniflorin (PF), liquiritin (LQ) and mono-ammonium glycyrrhizinate (GL) in test samples and samples of intestinal sac and intestinal perfusion was determined by HPLC. The intestinal absorptive amount and absorption parameters were calculated. Results showed that in the everted intestinal sac model, three ingredients could be absorbed by duodenum, jejunum and ileum, and the absorption in the jejunum was best for all 3 ingredients. The absorption rate of three ingredients in SG11 was significantly higher than that in single decoction (P absorption rate constant K(a), the apparent absorption coefficient P(app) and the absorption rate of three ingredients in SG11 were significantly higher than those in single decoction. Parameters of PF and GL in SG11 were significantly higher than those in SG31, but had no differences of LQ. It proved that the compatibility of Baishao and Zhigancao could improve the intestinal absorption of PF, LQ and GL. The absorption of each ingredient in SG11 was better than that in SG31.

  13. Fractional cholesterol absorption measurements in humans : Determinants of the blood-based dual stable isotope tracer technique

    NARCIS (Netherlands)

    Stellaard, Frans; Luetjohann, Dieter

    BACKGROUND: The flux of absorbed cholesterol is a controlling element in the regulation of cholesterol biosynthesis and catabolism. A review of 5 published methods to measure cholesterol absorption is presented, including 2 dual stable isotope approaches. The continuous dual isotope feeding

  14. Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease.

    Science.gov (United States)

    Qi, Yue; Liu, Jing; Ma, Changsheng; Wang, Wei; Liu, Xiaohui; Wang, Miao; Lv, Qiang; Sun, Jiayi; Liu, Jun; Li, Yan; Zhao, Dong

    2013-11-01

    No indices are currently available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment. We aimed to investigate whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin. Total 306 statin-naïve patients with high risk of coronary heart disease (CHD) were treated with atorvastatin 20 mg/day for 1 month. Cholesterol synthesis and absorption markers and LDL cholesterol (LDL-C) levels were measured before and after treatment. Atorvastatin decreased LDL-C by 36.8% (range: decrease of 74.5% to increase of 31.9%). Baseline cholesterol synthesis marker lathosterol and cholesterol absorption marker campesterol codetermined the effect of atorvastatin treatment. The effect of cholesterol lowering by atorvastatin was significantly associated with baseline lathosterol levels but modified bidirectionally by baseline campesterol levels. In patients with the highest baseline campesterol levels, atorvastatin treatment decreased cholesterol absorption by 46.1%, which enhanced the effect of LDL-C lowering. Atorvastatin treatment increased cholesterol absorption by 52.3% in those with the lowest baseline campesterol levels, which attenuated the effect of LDL-C reduction. Especially those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels (27.3% versus 42.4%, P = 0.002). These results suggest that combined patterns of cholesterol synthesis/absorption markers, rather than each single marker, are potential predictors of the LDL-C-lowering effects of atorvastatin in high-risk CHD patients.

  15. In vivo kinetics of intestinal absorption of riboflavin in rats

    International Nuclear Information System (INIS)

    Feder, S.; Daniel, H.; Rehner, G.

    1991-01-01

    To investigate absorption kinetics of riboflavin under in vivo conditions, with blood and lymph circulation intact, the small intestine of anesthetized rats was perfused with [ 14 C]riboflavin in a concentration range between 0.31 and 10.00 mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was determined. The absorption proved to be a dual process: at low substrate concentrations (less than 2 mumol/L) a saturable component predominated; at higher concentrations simple diffusion was found to be the prevailing uptake mechanism. The apparent transport constant of the saturable component was calculated to be 0.38 mumol/L. [ 14 C]flavin concentrations in the portal and peripheral blood were estimated as a function of the riboflavin concentration of the perfusion media. The dual character of the absorption was reflected by the portal blood flavin levels. Due to the high retaining and equalizing capacity of the liver, the [ 14 C]flavin level of the peripheral blood was relatively low and obeyed saturation kinetics. Constants of elimination, determined by pharmacokinetic calculations, were different for the two blood compartments but independent of the concentration of riboflavin in the perfusion media

  16. Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat

    International Nuclear Information System (INIS)

    Wang, Q.; Pantzar, N.; Jeppson, B.; Westroem, B.R.; Karlsson, B.W.

    1994-01-01

    The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. The different-sized intestinal absorption markers 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51 Cr-EDTA. In comparison with the sham-operated rats, septic rats had higher 51 Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. Thr results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit. 38 refs., 4 figs., 2 tabs

  17. Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats.

    Science.gov (United States)

    Zhou, Yan; Jiao, Yang; Wei, Yu-Hui; Zhang, Guo-Rong; Zhang, Jian-Ping; Ren, Jiang-Xia; Zhang, Fan; Zhang, Guo-Qiang; Duan, Hao-Gang; Wu, Xin-An

    2013-03-01

    Pyridoxine is always simultaneously administered orally with isoniazid for tuberculosis patients in the clinic to prevent or treat the nervous system side effects induced by isoniazid. So the aim of this research was to investigate the effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid. The intestinal absorption of isoniazid with or without pyridoxine was investigated by the rat single-pass intestinal perfusion model in situ, and a high-performance liquid chromatographic method was applied to study the pharmacokinetics of isoniazid with or without pyridoxine. The results suggested that the intestinal apparent permeability (P app) and intestinal absorption rate constant (K a) for isoniazid (30 μg/ml) were decreased by 43.7 and 36.4 %, respectively, by co-perfused pyridoxine (40 μg/ml). In vivo, the effect of pyridoxine on isoniazid pharmacokinetic correlated with the doses of pyridoxine. The blood concentrations of isoniazid at the absorption phase were affected by co-administered pyridoxine, but the AUC and C max of isoniazid were not greatly affected by pyridoxine as expected from the inhibition by pyridoxine of the intestinal absorption of isoniazid, which could be caused by its rapid absorption phase. Therefore, although the intestinal absorption of isoniazid could be significantly inhibited by pyridoxine, the pharmacokinetics of isoniazid oral administration was not greatly affected by the decreased intestinal absorption of isoniazid due to its rapid absorption.

  18. Effect of lactose on intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Labat, Marie-Louise

    1972-01-01

    Calcium absorption was immediately increased when lactose was administered in large amounts in the intestine of standard rats fed on a vitamin D diet. The same effect could be reproduced with lactulose, a glucid un-hydrolyzed by lactase and unabsorbed. The occurrence of a saturation process for high doses of calcium agrees with a biochemical process through a carrier; this process was not inhibited by actinomycin D, which does not agree with a 'de novo' synthesis of a calcium binding protein; yet activation of the preexisting protein cannot be excluded. The intestinal effect of lactose resulted in an inhibition of bone catabolism in the adult normocalcemic rat indicating a possible interference of thyrocalcitonin. Finally in the young rat, hypocalcemic by lack of vitamin D, on account of the lactose effect, calcium can be considered as a 'third messenger' in the chain of intracellular events between the interaction of the parathyroid hormone with the bone receptor and the expression of its activity. (author) [fr

  19. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish.

    Science.gov (United States)

    Semova, Ivana; Carten, Juliana D; Stombaugh, Jesse; Mackey, Lantz C; Knight, Rob; Farber, Steven A; Rawls, John F

    2012-09-13

    Regulation of intestinal dietary fat absorption is critical to maintaining energy balance. While intestinal microbiota clearly impact the host's energy balance, their role in intestinal absorption and extraintestinal metabolism of dietary fat is less clear. Using in vivo imaging of fluorescent fatty acid (FA) analogs delivered to gnotobiotic zebrafish hosts, we reveal that microbiota stimulate FA uptake and lipid droplet (LD) formation in the intestinal epithelium and liver. Microbiota increase epithelial LD number in a diet-dependent manner. The presence of food led to the intestinal enrichment of bacteria from the phylum Firmicutes. Diet-enriched Firmicutes and their products were sufficient to increase epithelial LD number, whereas LD size was increased by other bacterial types. Thus, different members of the intestinal microbiota promote FA absorption via distinct mechanisms. Diet-induced alterations in microbiota composition might influence fat absorption, providing mechanistic insight into how microbiota-diet interactions regulate host energy balance. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. The effect of wellsolve, a novel solubilizing agent, on the intestinal barrier function and intestinal absorption of griseofulvin in rats.

    Science.gov (United States)

    Hamid, Khuriah Abdul; Lin, Yulian; Gao, Yang; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2009-11-01

    The effect of Wellsolve, a new solubilizing agent, on the function of intestinal membrane barrier and transporters including P-glycoprotein (P-gp) and peptide transporter (PEPT1) was examined by an in vitro diffusion chamber and an in situ closed loop method. The model drugs used in this study were 5(6)-carboxyfluorescein (CF), rhodamine123 (a P-glycoprotein substrate), cephalexin (a typical substrate for PEPT1) and griseofulvin (a BCS Class II drug). Intestinal absorption of CF was not affected by the addition of 1-10% (v/v) Wellsolve, while 20% (v/v) Wellsolve significantly enhanced its intestinal absorption by the in situ absorption study. Therefore, this finding suggested that high concentration of Wellsolve might alter the intestinal barrier function. The mucosal to serosal (absorptive) and serosal to mucosal (secretory) transport of rhodamine123 was significantly inhibited in the presence of 5.0-20% (v/v) of Wellsolve, suggesting that Wellsolve might not affect the function of P-gp in the intestine. The intestinal transport of cephalexin was not affected in the presence of Wellsolve, suggesting that this solubilizing agent might not change the function of PEPT1 in the intestine. In the toxicity studies, we found that 1-10% (v/v) Wellsolve did not change the release of lactate hydrogenase (LDH) and protein from the intestinal membranes. Furthermore, intestinal absorption of griseofulvin in the presence of 10% (v/v) Wellsolve significantly increased as compared with the control. In summary, Wellsolve at lower concentrations might be a potent and safe solubilizing agent for improving the solubility and absorption of poorly water-soluble drugs including griseofulvin.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [Comparative study of absorption kinetics in intestines of rats on Xianlinggubao capsule prepared by different technologies].

    Science.gov (United States)

    Wu, Huichao; Du, Shouying; Lu, Yang; Chen, Wen; Ma, Yong; Li, Pengyue

    2011-04-01

    To study the characteristics of intestinal absorption of psoralen and isopsoralen of Xianlinggubao capsule, and compare the absorption of Xianlinggubao capsule prepared by different technologies. Non everted gut sac method was applied to investigate the influence of absorption sites and drug concentration on psoralen and isopsoralen absorption, which were determined by HPLC. Although the absorption rate constants of psoralen and isopsoralen in duodenum were more than that in jejunum and ileum, there was no significance difference between them. The absorption rate constants of psoralen kept at the same level when the concentrations of drug solution were at middle and low level, while the absorption rate constant at high level was absolutely lower than them (P Intestinal absorption of psoralen and isopsoralen may be affected by the dissolution. The absorption rate constants of psoralen and isopsoralen in new Xianlinggubao capsules are higher. The absorptions of active components absorption has significant difference in different preparation processes of Xianlinggubao capsule.

  3. [Recent knowledge about intestinal absorption and cleavage of carotenoids].

    Science.gov (United States)

    Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G

    2005-01-01

    Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the

  4. Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity1234

    Science.gov (United States)

    Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

    2011-01-01

    Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography–mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol–cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons. PMID:21940599

  5. [Study on intestinal absorption features of oligosaccharides in Morinda officinalis How. with sigle-pass perfusion].

    Science.gov (United States)

    Deng, Shao-Dong; Zhang, Peng; Lin, Li; Xiao, Feng-Xia; Lin, Jing-Ran

    2015-01-01

    To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum, jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results, all of the five oligosaccharides were absorbed in the whole intestine, and their absorption rates were affected by the pH of the perfusion solution, drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments, without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. [Study on intestinal absorption of formononetin in Millettia nitita var. hirsutissima in rats].

    Science.gov (United States)

    Liu, Ya-Li; Xiong, Xian-Bing; Su, Dan; Song, Yong-Gui; Zhang, Ling; Yang, Shi-Lin

    2013-10-01

    To use the single-pass intestine perfusion (SPIP) model and HPLC to determine the concentration of formononetin, the effect of quality concentrations of formononetin, different intestinal segments and P-glycoprotein inhibitor on intestinal absorption of formononetin, in order to observe the intestinal absorption mechanism of formononetin from Millettia nitita var. hirsutissima in rats. The experimental results showed that the qulaity concentration of formononetin in the perfusate had no significant effect on the absorption rate constant (K(a)) and the apparent absorption coefficient (P(app)); K(a) and P(app) of formononetin in duodenum, jejunum and ileum showed no significant difference. However, K(a) was significantly higher than that in colon (P intestinal segments (P absorption mechanism of formononein in rat intestinal tracts passive diffusion, without any saturated absorption. Formononein is absorbed well in all intestines. Their absorption windows were mainly concentrated in the intestinum tenue, without specific absorption sites. Formononein may be the substrate of P-glycoprotein.

  8. Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

    Directory of Open Access Journals (Sweden)

    Liu Xiao-Wei

    2011-07-01

    Full Text Available Abstract Background The hypocholesterolemic effects of lactic acid bacteria (LAB have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of Lactobacillus plantarum 9-41-A and Lactobacillus fermentum M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet. Methods Forty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum 9-41-A or Lactobacillus fermentum M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p Lactobacillus and Bifidobacterium colonies were increased while Escherichia coli colonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration of Lactobacillus plantarum 9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p Conclusions This study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, L. plantarum 9-41-A may play a role in fat metabolism.

  9. Coconut oil and sesame oil affect lymphatic absorption of cholesterol and fatty acids in rats.

    Science.gov (United States)

    Satchithanandam, S; Reicks, M; Calvert, R J; Cassidy, M M; Kritchevsky, D

    1993-11-01

    Five groups of male Wistar rats weighing approximately 200 g consumed 12 or 24% sesame oil or coconut oil diets or a control diet (14% corn oil) ad libitum for 4 wk. The thoracic ducts of these rats were cannulated, and a lipid emulsion containing [3H]cholesterol and [14C]oleic acid was given through a duodenal catheter. Lymph was collected for 24 h and the isotopic tracers for cholesterol and fatty acid were measured. Rats fed the 24% sesame oil diet had significantly lower lymphatic cholesterol and fatty acid compared with the control group. Absorption of oleic acid in rats fed 24% coconut oil was significantly greater than in controls during 0-8 h but was not significantly different during 0-24 h. There were no differences among groups in the distribution of cholesterol and oleic acid either in the lymph lipoproteins or in the lipid classes. The significant reduction in lymph cholesterol and fatty acids due to sesame oil feeding may be an important factor in reducing hypercholesterolemia.

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

    Science.gov (United States)

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

    2017-04-01

    LCA and 1,25(OH) 2 D 3 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.

  11. Mathematical Modeling of Intestinal Iron Absorption Using Genetic Programming.

    Science.gov (United States)

    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

  12. Impaired intestinal cholecystokinin secretion, a fascinating but overlooked link between coeliac disease and cholesterol gallstone disease.

    Science.gov (United States)

    Wang, Helen H; Liu, Min; Li, Xiaodan; Portincasa, Piero; Wang, David Q-H

    2017-04-01

    Coeliac disease is a chronic, small intestinal, immune-mediated enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Clinical studies have found that intestinal cholecystokinin secretion and gallbladder emptying in response to a fatty meal are impaired before coeliac patients start the gluten-free diet (GFD). However, it was never really appreciated whether coeliac disease is associated with gallstones because there were very few studies investigating the mechanism underlying the impact of coeliac disease on the pathogenesis of gallstones. We summarize recent progress on the relationship between coeliac disease and gallstones and propose that coeliac disease is an important risk factor for gallstone formation because defective intestinal cholecystokinin secretion markedly increases susceptibility to cholesterol gallstones via a mechanism involving dysmotility of both the gallbladder and the small intestine. Because GFD can significantly improve the coeliac enteropathy, early diagnosis and therapy in coeliac patients is crucial for preventing the long-term impact of cholecystokinin deficiency on the biliary and intestinal consequences. When gluten is reintroduced, clinical and histologic relapse often occurs in coeliac patients. Moreover, some of the coeliac patients do not respond well to GFD. It is imperative to routinely examine by ultrasonography whether gallbladder motility function is preserved in coeliac patients and monitor whether biliary sludge (a precursor of gallstones) appears in the gallbladder, regardless of whether they are under the GFD programme. To prevent gallstones in coeliac patients, it is urgently needed to investigate the prevalence and pathogenesis of gallstones in these patients. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  13. [Association between very low density lipoprotein cholesterol and cholesterol absorption/synthesis markers in patients with moderate and high risk of coronary heart disease].

    Science.gov (United States)

    Gong, Zhizhong; Qi, Yue; Zhao, Fan; Liu, Jing; Wang, Wei; Liu, Jun; Sun, Jiayi; Xie, Wuxiang; Li, Yan; Wang, Miao; Qin, Lanping; Wang, Ying; Hao, Yongchen; Zhang, Qingxuan; Chen, Xiaoping; Zhao, Dong

    2015-11-01

    To evaluate the association between very low density lipoprotein cholesterol (VLDL-C) and cholesterol absorption and synthesis markers in patients with moderate and high risk of coronary heart disease. A total 363 statin-naïve patients with moderate and high risk of coronary heart disease were consecutively recruited from two hospitals in Shanxi and Henan provinces between October 2008 and June 2009. A standard questionnaire and physical examination were performed at baseline. Atorvastatin (20 mg/day) was administered to patients for 4 weeks. Venous blood samples after an overnight fast were collected before and after treatment for measuring VLDL-C and cholesterol absorption and synthesis markers. In qualitative analyses, the baseline level of cholesterol absorption and synthesis markers and their reduction after atorvastatin treatment were categorized into 3 tertile groups. (1) Of 363 patients, 283 patients with mean age of (55.43±9.01)years old with complete data were finally analyzed. The median level of baseline VLDL-C was 1.06 (0.65, 1.86) mmol/L. The median level of baseline cholesterol absorption marker (Campesterol) and cholesterol synthesis marker (Lathosterol) was 6.01 (3.78, 9.45) mg/L and 13.46 (8.30, 21.07) mg/L, respectively. (2) Partial correlation analysis and multiple regression showed the baseline level of VLDL-C was positively correlated with Campesterol (r=0.153, Pmarker, and further studies are needed to validate if inhibitor of cholesterol absorption (for example by Ezetimibe) could bring about more effective VLDL-C lowering effect in this patient cohort.

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

    Science.gov (United States)

    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.

  15. The origin of cholesterol in chyle demonstrated by nuclear indicator methods; Origines du cholesterol du chyle mises en evidence par la methode des indicateurs nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Vyas, M

    1962-07-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-{sup 14}C- cholesterol subcutaneously or orally, or the 1-{sup 14}C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [French] Pour obtenir des renseignements concernant le mecanisme de l'absorption intestinale du cholesterol, on utilise des rats porteurs d'une fistule lymphatique abdominale. Les animaux recoivent soit du cholesterol 4-{sup 14}C par voie sous-cutanee ou par voie orale, soit de l'acetate 1-{sup 14}C. L'etude des radioactivites specifiques du cholesterol du chyle, du serum, de la paroi et du contenu intestinal permet de preciser les roles joues par le cholesterol de transfert d'origine serique, par le cholesterol de synthese intestinale et par le cholesterol d'absorption, dans la formation de la lymphe et des chylomicrons. Une theorie nouvelle concernant le mecanisme de l'absorption du cholesterol est proposee. (auteur)

  16. Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe.

    Science.gov (United States)

    Zhang, Tao; Wu, Wen-feng; Liu, Yang; Wang, Qi-hui; Wang, Lü-ya; Mi, Shu-hua

    2013-01-01

    Statins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease. Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography. After treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

  17. [Determination method of muscone in rat intestinal perfusate by GC-MS/MS and its intestinal absorption kinetic characteristics in rats].

    Science.gov (United States)

    Zou, Liang; Lin, Junzhi; Wang, Zhanguo; Xu, Lijia; Wang, Ping; Zhao, Gang; Luo, Jieying

    2012-08-01

    To establish the method for determining muscone in rat intestinal perfusate by GC-MS/MS and study its intestinal absorption kinetic characteristics in rats. The GC-MS/MS method was used to determine the content of muscone in rat intestinal circulation fluid. In situ intestinal circulation perfusion was adopted to study absorption kinetics of muscone in rats. Muscone was proved to be well absorbed in each section of small intestine. Its absorption rate constants (Ka) and the absorption rate (A) in the rat intestine showed duodenum > jejunum (P ileum (P intestine was 0.990 h(-1) , 43.58% and 0.705h, respectively. Muscone was well absorbed in each intestinal section, with duodenum better than jejunum (Ka, T1/2, P < 0.05) significantly better than ileum (Ka, T1/2, P < 0.01; A, P < 0.05). There is no obvious statistical difference between jejunum and ileum.

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

    Science.gov (United States)

    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.

  19. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Science.gov (United States)

    2012-01-01

    Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w) cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load. PMID:22394543

  20. Comparable reduction in cholesterol absorption after two different ways of phytosterol administration in humans.

    Science.gov (United States)

    Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

    2013-04-01

    Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE-minidrink, p < 0.0001) compared with the control meal. PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.

  1. Adaptation of intestinal calcium absorption: parathyroid hormone and vitamin D metabolism

    International Nuclear Information System (INIS)

    Ribovich, M.L.; DeLuca, H.F.

    1978-01-01

    It has already been demonstrated that the adaptation of intestinal calcium absorption of rats on a low calcium diet can be eliminated by thyroparathyoidectomy plus parathyroid hormone administration. It therefore appears likely that the modulation of intestinal calcium absorption by dietary calcium is mediated by the parathyroid glands and the renal biogenesis of 1,25-dihydoxyvitamin D 3 . Changes in the other unknown vitamin D metabolite levels as a result of dietary calcium are also modified by thyroparathyroidectomy and parathyroid hormone administration, but the effect of these metabolites on intestinal calcium transport is unknown

  2. Luminal calcium concentration controls intestinal calcium absorption by modification of intestinal alkaline phosphatase activity.

    Science.gov (United States)

    Brun, Lucas R; Brance, María L; Rigalli, Alfredo

    2012-07-01

    Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. IAP expression parallels that of other proteins involved in Ca absorption under vitamin D stimulation. Experiments carried out in vitro with purified IAP have demonstrated an interaction between Ca and IAP. The gut is prepared to face different levels of Ca intake over time, but high Ca intake in a situation of a low-Ca diet over time would cause excessive entry of Ca into the enterocytes. The presence of a mechanism to block Ca entry and to avoid possible adverse effects is thus predictable. Thus, in the present study, Sprague-Dawley rats were fed with different amounts of Ca in the diet (0.2, 1 and 2 g%), and the percentage of Ca absorption (%Ca) in the presence and absence of L-phenylalanine (Phe) was calculated. The presence of Phe caused a significant increase in %Ca (52.3 (SEM 6.5) % in the presence of Phe v. 31.1 (sem 8.9) % in the absence of Phe, regardless of the amount of Ca intake; paired t test, P = 0.02). When data were analysed with respect to Ca intake, a significant difference was found only in the group with low Ca intake (paired t test, P = 0.03). Additionally, IAP activity increased significantly (ANOVA, P < 0.05) as Ca concentrations increased in the duodenal lumen. The present study provides in vivo evidence that luminal Ca concentration increases the activity of IAP and simultaneously decreases %Ca, acting as a minute-to-minute regulatory mechanism of Ca entry.

  3. Kinetic stability and membrane structure of liposomes during in vitro infant intestinal digestion: Effect of cholesterol and lactoferrin.

    Science.gov (United States)

    Liu, Weilin; Wei, Fuqiang; Ye, Aiqian; Tian, Mengmeng; Han, Jianzhong

    2017-09-01

    The effects of cholesterol and lactoferrin on the kinetic stability and membrane structural integrity of negatively charged liposomes under in vitro infant intestinal digestion conditions were elucidated using dynamic light scattering, pH-stat titration, Fourier transform infrared spectroscopy, and pyrene steady state fluorescence probes. The liposomes had a smaller particle diameter, a wider size distribution, and a greater negative charge after digestion. The incorporation of cholesterol into the phospholipid bilayers resulted in a more ordered conformation in the aliphatic tail region and reduced micropolarity, indicating that cholesterol can improve the structural stability of liposomal membranes against intestinal environmental stress. Lactoferrin coverage facilitated the release of free fatty acids and increased the microfluidity of the bilayers, reducing the structural integrity of the liposomes. This study provides useful information on the design of liposomes and other microcapsules with improved and controlled release properties during digestion for particular groups of people. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    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. PMID:25231105

  5. Impact of co-administration of protonated nanostructured aluminum silicate (cholesterol absorption inhibitor) on the absorption of lipid soluble vitamins D3 and K1: an assessment of pharmacokinetic and in vitro intraluminal processing.

    Science.gov (United States)

    Ibrahim, Fady; Sivak, Olena; Wong, Carly; Hopkins, Patrick; Midha, Ankur; Gordon, Jacob; Darlington, Jerald W; Wasan, Kishor M

    2013-05-13

    Protonated nanostructured aluminum silicate (NSAS) is a protonated montmorillonite clay that was shown to be effective as an inhibitor of intestinal cholesterol absorption. The effect of NSAS on the intestinal absorption of nutrients is unknown. An in vitro lipolysis model was adapted to test the intraluminal processing of vitamin D3 and K1 in the presence of various amounts of NSAS. Additionally, vitamin absorption was assessed in male Sprague-Dawley rats randomized in the following treatment groups: IV administration of 0.1 mg/kg vitamin D3 and 1 mg/kg vitamin K1, and a single-dose gavage of 1 mg/kg vitamin D3 and 5mg/kg of vitamin K1 in peanut oil with various doses of NSAS slurry, 2% NSAS-fortified diet, or 50 mg/kg stigmastanol. The solubilized fraction of vitamin D3 in the lipolysis medium was reduced from 70% to 46% upon the addition of 120 mg NSAS. In contrast, the solubilized fractions of vitamin K1 were not significantly affected. Although the NSAS-fortified diet did not significantly affect the absorbed fraction of both vitamins, NSAS slurry decreased the absorption of vitamin D3 as compared to the control. These results indicate that NSAS may be incorporated in diet to treat hypercholesterolemia; however, vitamin D3 monitoring may be required. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Dietary cholesterol-induced transcriptome differences in the intestine, hepatopancreas, and muscle of Oriental River prawn Macrobrachium nipponense.

    Science.gov (United States)

    Gu, Xizhang; Fu, Hongtuo; Sun, Shengming; Qiao, Hui; Zhang, Wenyi; Jiang, Sufei; Xiong, Yiwei; Jin, Shubo; Gong, Yongsheng; Wu, Yan

    2017-09-01

    Cholesterol is an important nutrient for crustaceans. In this study, we performed comparative transcriptome analyses to explore the transcriptome differences in the intestine, hepatopancreas, and muscle of Macrobrachium nipponense fed either a low cholesterol (LC) or high cholesterol (HC) diet (2.8 or 17.1g cholesterol per kg diet). High-throughput RNA-Seq was conducted, resulting in 7.65, 5.88, and 7.59G clean bases from the intestine, hepatopancreas, and muscle of the LC group, respectively, and 7.59, 6.73, and 6.70G clean bases from the same tissues of the HC group. Assembly of clean reads resulted in 230,946 unigenes. The following enriched pathways were identified: xenobiotic and drug metabolism by cytochrome P450; chloroalkane and chloroalkene degradation; metabolic and biosynthetic pathways; fatty acid metabolism and biosynthesis; and immune-related pathways. To the best of our knowledge, this is the first study to describe how functional unigenes and biosynthetic and metabolic pathways are affected by dietary cholesterol in aquatic crustaceans. Thus, these results contribute to our understanding of the molecular mechanisms underlying the cholesterol requirement of crustaceans. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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

  9. Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data.

    Science.gov (United States)

    Sjögren, Erik; Dahlgren, David; Roos, Carl; Lennernäs, Hans

    2015-06-01

    Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans. Plasma concentration-time profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal Peff estimates and jejunal Peff measurements determined directly using the single-pass perfusion double balloon technique. On average, Peff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal Peff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making.

  10. [Intestinal absorption of different combinations of active compounds from Gegenqinlian decoction by rat single pass intestinal perfusion in situ].

    Science.gov (United States)

    An, Rui; Zhang, Hua; Zhang, Yi-Zhu; Xu, Ran-Chi; Wang, Xin-Hong

    2012-12-01

    The aim is to study the intestinal absorption of different combinations of active compounds out of Gegenqinlian decoction. Rat single pass intestinal perfusion model with jugular vein cannulated was used. Samples were obtained continuously from the outlet perfusate and the mesenteric vein. The levels of puerarin, daidzin, liquilitin, baicalin, wogonoside, jatrorrhizine, berberine and palmatine were determined by LC-MS/MS and their permeability coefficients were calculated. The results showed that Glycyrrhiza could promote the absorption of the active ingredients in Pueraria which is the monarch herb; meanwhile, Pueraria also played a role in promoting the absorption of liquilitin. Based on the Gegenqinlian decoction and the different combinations experiments, the results concerning the absorption of baicalin and wogonoside were as follows. For baicalin, Pueraria and Glycyrrhiza could promote its absorption and the effect of Pueraria was more obvious. For wogonoside, Pueraria could also promote its absorption, while Glycyrrhiza played a opposite role. Pueraria and Glycyrrhiza both played a part in promoting the absorption of jateorhizine, berberine and palmatine, the effective compounds in Coptis.

  11. A new cholesterol biosynthesis and absorption disorder associated with epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration.

    Science.gov (United States)

    Korematsu, Seigo; Uchiyama, Shin-ichi; Honda, Akira; Izumi, Tatsuro

    2014-06-01

    Cholesterol is one of the main components of human cell membranes and constitutes an essential substance in the central nervous system, endocrine system, and its hormones, including sex hormones. A 19-year-old male patient presented with failure to thrive, psychomotor deterioration, intractable epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration. His serum level of cholesterol was low, ranging from 78.7 to 116.5 mg/dL. The serum concentrations of intermediates in the cholesterol biosynthesis pathway, such as 7-dehydrocholesterol, 8-dehydrocholesterol, desmosterol, lathosterol, and dihydrolanosterol, were not increased. In addition, the levels of the urinary cholesterol biosynthesis marker mevalonic acid, the serum cholesterol absorption markers, campesterol and sitosterol, and the serum cholesterol catabolism marker, 7α-hydroxycholesterol, were all low. A serum biomarker analysis indicated that the patient's basic abnormality differed from that of Smith-Lemli-Opitz syndrome and other known disorders of cholesterol metabolism. Therefore, this individual may have a new metabolic disorder with hypocholesterolemia because of decreased biosynthesis and absorption of cholesterol. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins: Cellular and Molecular Aspects

    DEFF Research Database (Denmark)

    Nexø, Ebba; Said, Hamid M

    2012-01-01

    The water-soluble vitamins represent a group of structurally and functionally unrelated compounds that share the common feature of being essential for normal cellular functions, growth, and development. With the exception of some endogenous production of niacin, human cells cannot synthesize...... these micronutrients, and thus, must obtain them from exogenous sources via intestinal absorption. The intestine, therefore, plays a critical role in maintaining and regulating normal body homeostasis of these essential nutrients, and interference with its normal absorptive function could lead to suboptimal states...... or deficiency. An impaired absorptive function occurs in a variety of conditions including congenital defects in the digestive or absorptive processes, intestinal diseases, drug interaction, and chronic alcohol use....

  13. Differential effects of paricalcitol and calcitriol on intestinal calcium absorption in hemodialysis patients.

    Science.gov (United States)

    Lund, Richard J; Andress, Dennis L; Amdahl, Michael; Williams, Laura A; Heaney, Robert P

    2010-01-01

    Increased parathyroid activity associated with chronic kidney disease is often managed with calcitriol, which can elevate serum calcium (Ca) by increasing bone resorption and intestinal absorption, whereas paricalcitol promotes less bone resorption. This study compared intestinal Ca absorption in hemodialysis patients treated with calcitriol versus paricalcitol (dose ratio 1:3). Patients (n = 22) aged > or =20 years, on maintenance hemodialysis for > or =2 months with intact parathyroid hormone (iPTH) levels of >200 pg/ml were enrolled in a single-center, double-blind, active-controlled, randomized, crossover trial. Mean fractional intestinal Ca absorption (+/-SE) was measured by the single-tracer method ((42)Ca) and evaluated with an analysis of variance crossover model. Mean fractional intestinal Ca absorption was significantly lower after paricalcitol (0.135 +/- 0.006) versus calcitriol treatment (0.158 +/- 0.006, p = 0.022), a 0.023 difference in absolute Ca absorption fraction. Overall Ca absorption was low in the study population, indicating that regulation of Ca absorption may be dysfunctional. There were no significant differences in serum PTH, Ca, phosphorus (P), or Ca x P. Overall, paricalcitol-treated patients absorbed approximately 14% less Ca compared with calcitriol-treated patients with similar effects on PTH. In hemodialysis patients, paricalcitol may provide a benefit by lowering the Ca available for removal by dialysis and/or for deposit in bone or soft tissues. Copyright (c) 2009 S. Karger AG, Basel.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. [Production, absorption and excretion of phenols in intestinal obstruction].

    Science.gov (United States)

    Kawamoto, M

    1986-11-01

    In intestinal obstruction, phenols were produced in the distended loop proximal to obstruction by enteric bacteria. Clinically, in 17 cases of non-strangulated intestinal obstruction, phenols were detected in 15 cases and mean concentration of phenols was 4.2 +/- 9.7 micro g/ml(mean +/- 1 SD). In the fraction of phenols, p-cresol was detected in 15 cases and mean concentration was 3.8 +/- 7.7 and phenol was detected in 4 cases and mean concentration was 0.5 +/- 2.6. Phenols were decreased as clinical improvement of intestinal obstruction. Enteric bacteria in enteric juice ranged from 10(4) to 10(10)/ml and its change paralleled to phenols concentration. Mean urinary concentration of phenols in intestinal obstruction was increased to 297 +/- 415 mg/day compared to control (less than 50 mg/day). Its change also paralleled to phenols concentration in enteric juice. Closed ileal loop was made in dogs and phenols were infused in the loop. Phenols were increased in the portal vein 5 min after the infusion and in the femoral vein 60 min after the infusion. Phenols, which was thought to be toxic to the host, were proved to be produced in the distended intestine and excreted from the kidney.

  16. Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs

    NARCIS (Netherlands)

    Tryfonidou, M.A.; Stevenhagen, J.J.; Bemd, G.J.C.M. van den; Oosterlaken-Dijksterhuis, M.A.; Deluca, H.F.; Mol, J.A.; Brom, W.E. van den; Leeuwen, J.P.T.M. van; Hazewinkel, H.A.W.

    2002-01-01

    Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D3)supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 μg vitamin D3/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in

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

    Science.gov (United States)

    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. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Intestinal absorption of water-soluble vitamins in health and disease

    Science.gov (United States)

    Said, Hamid M.

    2014-01-01

    Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current

  19. Intestinal absorption of dinitrophenyl-lysine and effect of immunization with dinitrophenylated bovine serum albumin

    International Nuclear Information System (INIS)

    Shimura, Fumio; Shimura, Junko; Shimazaki, Shigeki; Hosoya, Norimasa

    1983-01-01

    The intestinal absorption of dinitrophenyl-lysine (DNP-lys) was studied with a special interest on the role of the immune system in the absorption of small molecules which are recognized as nonself. [ 3 H]-DNP- lys was rapidly absorbed by ligated intestinal loops in situ via a saturable and unique route. When [ 3 H]-DNP-lys was preincubated with the immume serum obtained from rats immunized with dinitrophenylated bovine serum albumin (DNP-BSA), the [ 3 H]-DNP-lys absorption was depressed. The absorption of [ 3 H]-DNP-lys in DNP-BSA-immunized rats was depressed compared to the control. The results obtained suggest that the immune system play a role in avoiding the absorption of small molecules with antigenicity. (author)

  20. Clinical studies of intestinal /sup 47/Ca absorption test by external arm counter

    Energy Technology Data Exchange (ETDEWEB)

    Ebisuno, Shoichi; Morimoto, Shigeyoshi; Torizumi, Kazutami; Yamada, Ryusaku; Ohta, Kiichiro; Ohkawa, Tadashi

    1984-08-01

    An arm counter used to measure fractional accumulation of /sup 47/Ca on the forearm following an intravenous and a later oral dose of the radioisotope, and the intestinal /sup 47/Ca absorption rate was calculated. Clinical studies were carried out in normal subjects and patients with some disorders of calcium metabolism, using this external counting techinique. In 12 healthy control men (mean age 31.8 y), calcium absorption rate ranged from 42.5% to 59.6%. In 6 healthy women (mean age 31.4 y), the rate ranged from 46.8% to 57.3%. The intestinal calcium absorption was not related to the sex in younger adults. The fractional absorption of calcium was significantly increased in patients with primary hyperparathyroidism, whereas it was reduced in hypoparathyroidism. In 5 female subjects affected by osteoporosis, a defective intestinal absorption of calcium was observed. The calcium absorption tests were carried out on normo- and hypercalciuric patients with calcium urolithiasis. Higher absorption of calcium was recognized in some hypercalciuric patients. In hypercalciuric calcium stone formers with rice-bran treatment, /sup 47/Ca absorption from the gut was decreased significantly.

  1. Measurement of Intestinal and Peripheral Cholesterol Fluxes by a Dual-Tracer Balance Method

    NARCIS (Netherlands)

    Ronda, Onne A H O; van Dijk, Theo H; Verkade, H J; Groen, Albert K

    2016-01-01

    Long-term elevated plasma cholesterol levels put individuals at risk for developing atherosclerosis. Plasma cholesterol levels are determined by the balance between cholesterol input and output fluxes. Here we describe in detail the methodology to determine the different cholesterol fluxes in mice.

  2. Clinical studies of intestinal 47Ca absorption test by external arm counter

    International Nuclear Information System (INIS)

    Ebisuno, Shoichi; Morimoto, Shigeyoshi; Torizumi, Kazutami; Yamada, Ryusaku; Ohta, Kiichiro; Ohkawa, Tadashi

    1984-01-01

    An arm counter used to measure fractional accumulation of 47 Ca on the forearm following an intravenous and a later oral dose of the radioisotope, and the intestinal 47 Ca absorption rate was calculated. Clinical studies were carried out in normal subjects and patients with some disorders of calcium metabolism, using this external counting techinique. The following results were obtained; (1) In 12 healthy control men (mean age 31.8 y), calcium absorption rate ranged from 42.5% to 59.6% (mean+-SD; 54.1+-4.7%). In 6 healthy women (mean age 31.4 y), the rate ranged from 46.8% to 57.3% (mean+-SD; 51.3+- 4.3%). The intestinal calcium absorption was not related to the sex in younger adult. (2) The fractional absorption of calcium were significantly increased in patients with primary hyperparathyroidism, whereas reduced in hypoparathyroidism. (3) In 5 female subjects affected by osteoporosis, a defective intestinal absorption of calcium was observed. (4) The calcium absorption tests were carried out on normo- and hypercalciuric patients with calcium urolithiasis. Higher absorption of calcium was recognized in some hypercalciuric patients. (5) In hypercalciuric calcium stone formers with rice-bran treatment, 47 Ca absorption from gut were decreased significantly. (6) This method is very convenient to determine the intestinal absorption of 47 Ca. When a protective covering of lead is prepared for scintiscanner, the 47 Ca absorption test can be done for the patients with calcium metabolic disorder on a routine examination. (author)

  3. Catecholamines potentiate the effect of thyroid hormone on intestinal absorption of glucose in the rat.

    Science.gov (United States)

    Olaleye, S B; Elegbe, R A

    2005-06-01

    The study is to investigate the role of catecholamines on the increased absorption of glucose from the gut by thyroxine, the effect of graded doses of adrenaline and noradrenaline on glucose absorption was studied in euthyroid (ET), hyperthyroid (TH-) and hypothyroid rats (Thx). Glucose absorption was deduced in vivo from intestinal segment perfused with Kreb's bicarbonate solution containing 5.6 mM glucose and in vitro using the everted sac technique. In vivo, basal glucose absorption was significantly increased in the hyperthyroid and decreased in the hypothyroid rats (1.97 +/- 0.19 mM/g, P<0.01, and 0.92 +/- 0.10 mM/g, p<0.05 respectively) when compared with the euthyroid group (1.34 +/- 0.15 mM/g). Adrenaline (20 mg/dl - 80 mg/dl) increased glucose absorption in a dose dependent manner in all the groups. However, the responsiveness of the gut glucose absorption to adrenaline (as evidenced by the dose producing half- maximal absorption or ED50) was reduced by thyroidectomy (ED50 = 26.09 mg/100 ml) and increased by chronic thyroxine treatment (ED50 = 11.13 mg/100 ml). The ED50 in the euthyroid animals was 14.6 mg/100 ml. In vitro, glucose absorption from the isolated segments in both Thx and TH- rats were significantly reduced (P<0.05). Incubation of the isolated intestinal segments with graded doses of adrenaline caused a significan and dose related increases in glucose absorption. However thyroidectomy shifted the dose-response curve for glucose uptake from the isolated intestinal sac incubated with adrenaline to the right of the curve for euthyroid rats. It is concluded that catecholamines may play a role in the increase in intestinal absorption by thyroid hormones.

  4. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  5. Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

    Science.gov (United States)

    McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

    2005-01-01

    Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands. PMID:17148346

  6. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats

    Science.gov (United States)

    Morrone, Maurilio da Silva; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; da Boit Martinello, Katia; Saldanha Henkin, Bernardo; Rabello, Thallita Kelly; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-01-01

    The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause. PMID:26640615

  7. Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice.

    Science.gov (United States)

    Wang, Ming-Yu; Yang, Ming; Hou, Pi-Yong; Chen, Xiu-Bo; Li, Hong-Gang; Yan, Jiu-Xing; Zhang, Jun; Zhang, Yan-Wen; Wu, Xiao-Hui

    2017-08-03

    1. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be very effective in hyperuricemic control. But it is poorly bioavailable after oral administration. Here, we determined the role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D. 2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity in vitro ATPase assay with a small EC 50 value of 0.46 μM. 3. In the single-pass perfused mouse intestine model, the absorption of Pallidifloside D was not favored in the small intestine (duodenum, jejunum and ileum) with a P* w value of 0.35-0.78. By contrast, this compound was well-absorbed in the colon with a P* w value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum, ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of Pallidifloside D by a 2.5-fold after oral administration. 4. These results suggest that P-gp-mediated efflux is a limiting factor for intestinal absorption of Pallidifloside D in mice.

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

    Science.gov (United States)

    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.

  9. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    Directory of Open Access Journals (Sweden)

    Jungsuwadee Paiboon

    2011-02-01

    Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

  10. [Study on effect of oligochitosan in promoting intestinal absorption of protoberberine alkaloids in extracts from Corydalis saxicola total alkaloids].

    Science.gov (United States)

    Li, Xin-yang; Xie, Hui; Lu, Tu-lin; Shi, Yue-jiao; Zhang, Xing-de; Liu, Ting

    2015-05-01

    To investigate the effect of oligochitosan in promoting intestinal absorption of protoberberine alkaloids in extracts from Corydalis saxicola total alkaloids. The in vitro single-pass intestinal perfusion model in rats was established to study the changes in absorption kinetic parameters of dehydrocavidine, berberine hydrochloride and palmatine chloride in C. saxicola total alkaloids after the addition of different concentrations oligochitosan and evaluate the effect of oligochitosan in promoting intestinal absorption of the drugs. The concentration of oligochitosan had different effects on the absorption rate constant (Ka) and apparent permeability coefficient (Peff) of the three active component in rat intestines. Ka and Peff in 0.5% oligochitosan group significantly increased, indicating a stronger effect in promoting the absorption. Oligochitosan has a certain effect in promoting the intestinal absorptions of protoberberine alkaloids in C. saxicola total alkaloids.

  11. Tests of intestinal absorption using carbon-14-labeled isotopes

    International Nuclear Information System (INIS)

    Fromm, H.; Sarva, R.P.

    1983-01-01

    Beta radiation-emitting isotopes are being used increasingly in diagnostic gastroenterology for the study of absorption. The major reason for the popularity of radioisotopes is that their use is convenient for patient and physician alike. They often obviate naso- or orointestinal intubation and the collection, storage, and analysis of stool. The radioactivity used for the studies of digestive and absorptive processes is small and is not hazardous. In spite of the safety of the radiolabeled compounds, their use is restricted in children and pregnant women. Therefore, for most tests, promising alternative methods that make use of the stable isotope of carbon, /sup 13/C, instead of the radioactive /sup 14/C have been developed. The analysis of stable isotopes requires more sophisticated technology than that of radioactive compounds, however. Only a few centers presently are equipped and staffed to analyze stable isotopes on a routine basis. In contrast, the analysis of radioactive isotopes has become a routine procedure in almost ever major laboratory. The last decade has brought the development of several radioactive absorption tests. The clinically most useful tests relate to the study of bile acid, fat, lactose, and xylose absorption. All of these tests utilize the excretion rate of /sup 14/CO/sub 2/ in breath after ingestion of a /sup 14/C-labeled compound as a measure of the rate of its absorption or malabsorption

  12. Intestinal absorption of calcium and magnesium in rats

    International Nuclear Information System (INIS)

    Erhart, J.

    1981-01-01

    Absorption of Ca and Mg was studied in isolated and perfused jejunum segments of rats using radioactive 45 Ca and 28 Mg. At ion concentrations of 1.5 and 10 mmol in the bath solution, the influence of uraemia, 1,25-(OH) 2 D 3 and the complementary ion was investigated. Absorption of Ca ++ was found to be slightly reduced by uraemia and renormalized by 1,25-(OH) 2 D 3 substitution. Transport of Ca ++ was significantly increased in the presence of Mg ++ , both in healthy rats and in animals with chronic uraemia. Mg ++ absorption, in contrast, was significantly reduced in rats with uraemia, and 1,25-(OH) 2 D 3 substitution was found to reduce it even further. In the presence of Ca ++ , transport of Mg ++ was lowered both in healthy rats and in rats with chronic uraemia. (MG) [de

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

    International Nuclear Information System (INIS)

    Mason, J.B.; Selhub, J.

    1986-01-01

    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 3 pteryolmonoglutamate (H 3 PGA) was examined in suckling rats by the intestinal loop model. Unbound H 3 PGA demonstrated greater lumenal disappearance in the proximal segment of the small intestine compared to the distal segment (79% vs. 56%, P 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

  14. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

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

    2017-01-01

    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 intestinal 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. 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. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    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 (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 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.

  16. Effect of enteric micro-organisms on intestinal sugar and fatty acid absorption.

    Science.gov (United States)

    Burke, V; Houghton, M; Gracey, M

    1977-08-01

    The effect of micro-organisms contaminating the upper intestinal contents of malnourished children on intestinal absorption of 3-0 methyl-alpha-D-glucopyranose (3-M.G.) and oleic acid was studied in rats in vivo. Oleci acid absorption was unaffected by non-pathogenic E. coli but decreased by E. coli 0111, Salmonella paratyphi B., Shigella sonnei and Candida sp. This effect was probably explained by intestinal secretion diluting the test solution leading to a decreased diffusion gradient for solubilised fatty acid. Inhibition of sugar absorption occurred with bacterial suspensions of Staphylococcus aureus, Streptococcus faecalis, E. coli and Candida sp. and cell-free preparations of Staphylococcus aureus, Streptococcus faecalis, a non-pathogenic E. coli, Proteus sp., Klebsiella sp., Pseudomonas sp. and Candida sp. These effects were not explained by dilution of the test solution. This indicates that numerous micro-organisms and, in some instances, their cell-free preparations can interfere with intestinal active sugar transport. These findings may be relevant to the production of malabsorption in malnourished children who have a wide variety of micro-organisms contaminating their upper intestinal contents.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-07-15

    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. 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 contamination

  19. Study on intestinal /sup 47/Ca absorption test by employing scintillation camera

    Energy Technology Data Exchange (ETDEWEB)

    Torizumi, K.; Yamada, R.; Ota, K.; Ebisuno, S.

    1987-05-01

    In order to evaluate the clinical application of the calcium absorption test from the intestine, the intestinal /sup 47/Ca absorption test by using a scintillation camera was carried out in our laboratory. The results in the intestinal /sup 47/Ca absorption test using a scintillation camera showed a good correlation to the results which were estimated by using an arm counter previously reported by us. The rate of intestinal /sup 47/Ca absorption in 8 healthy volunteers (5 male, 3 female, average age: 37.6 +- 9.5 years) was 52.0 +- 3.8 %, 74.3 % in a patient with primary hyperparathyroidism 30.4 %, and 32.7 % in two patients with idiopathic hypoparathyroidism respectively. This method is more easily handled and can be performed for only 4 days in institutes that are set up with scintillation camera without any special preparations, and it is recommended to be of clinical usefulness for the diagnosis of calcium metabolic disorders.

  20. A study on intestinal 47Ca absorption test by employing scintillation camera

    International Nuclear Information System (INIS)

    Torizumi, Kazutami; Yamada, Ryusaku; Ota, Kiichiro; Ebisuno, Shoichi

    1987-01-01

    In order to evaluate the clinical application of the calcium absorption test from the intestine, the intestinal 47 Ca absorption test by using a scintillation camera was carried out in our laboratory. The results in the intestinal 47 Ca absorption test using a scintillation camera showed a good correlation to the results which were estimated by using an arm counter previously reported by us. The rate of intestinal 47 Ca absorption in 8 healthy volunteers (5 male, 3 female, average age: 37.6 ± 9.5 years) was 52.0 ± 3.8 %, 74.3 % in a patient with primary hyperparathyroidism 30.4 % and 32.7 % in two patients with idiopathic hypoparathyroidism respectively. This method is more easily handled and can be performed for only 4 days in institutes that are set up with scintillation camera without any special preparations, and it is recommended to be of clinical usefulness for the diagnosis of calcium metabolic disorders. (author)

  1. Follow-up of treated coeliac patients: Sugar absorption test and intestinal biopsies compared

    NARCIS (Netherlands)

    Uil, J. J.; van Elburg, R. M.; van Overbeek, F. M.; Meyer, J. W.; Mulder, C. J.; Heymans, H. S.

    1996-01-01

    Objective: To determine whether the sugar absorption test (SAT) during follow-up of patients with coeliac disease on a gluten-free diet (GFD) correlates with improvement of the villous architecture of the small intestine. Methods: The SAT was performed in coeliacs at diagnosis and during follow-up

  2. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    Ribovich, M.L.; DeLuca, H.F.

    1978-01-01

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D 3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D 3 , 24,25-dihydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , 25,26-dihydroxyvitamin D 3 , and 1,24,25-trihydroxyvitamin D 3 ), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 , the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

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

    Science.gov (United States)

    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. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine.

    Science.gov (United States)

    Jattan, Javeed; Rodia, Cayla; Li, Diana; Diakhate, Adama; Dong, Hongli; Bataille, Amy; Shroyer, Noah F; Kohan, Alison B

    2017-05-01

    Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken. Here we report that primary murine enteroid cultures recapitulate in vivo intestinal lipoprotein synthesis and secretion, and reflect key aspects of the physiology of intact intestine in regard to dietary fat absorption. We also show that enteroids can be used to elucidate intestinal mechanisms behind CVD risk factors, including tissue-specific apolipoprotein functions. Using enteroids, we show that intestinal apoC-III overexpression results in the secretion of smaller, less dense chylomicron particles along with reduced triacylglycerol secretion from the intestine. This model significantly expands our ability to test how specific genes or genetic polymorphisms function in dietary fat absorption and the precise intestinal mechanisms that are critical in the etiology of metabolic disease. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium.

    Science.gov (United States)

    Yin, Yong-Mei; Cui, Fu-De; Kim, Jung Sun; Choi, Min-Koo; Choi, Byung Chul; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2009-01-01

    A redispersible dry emulsion (DE) formulation of atorvastatin calcium (AC) was developed to enhance the in vitro dissolution of AC, thereby increasing its gastrointestinal absorption. The spray-drying technology was used where Plurol Oleique CC 497 was chosen as the oil phase. Effects of carriers, surfactants, and homogenizers on the characteristics of DE containing AC were systematically investigated. The final formulation consisted of dextrin and Poloxamer 188 as carrier and surfactant, respectively, and was homogenized by a high pressure homogenizer before spray drying. The in vitro release of AC from the optimized DE was significantly higher than that of pure AC powder (76% vs. 30% at 24 hr). The in vitro intestinal absorption of AC from the DE formulation was 0.77 microg/cm(2) at 2 hr, which was a 2.33-fold increase compared to the pure unformulated AC powder. These results suggest that the oral dry emulsion formulation could improve the intestinal absorption of AC.

  6. Therapeutic effect of an elemental diet on proline absorption across the irradiated rat small intestine

    International Nuclear Information System (INIS)

    Mohiuddin, M.; Kramer, S.

    1978-01-01

    Active absorption of [ 3 H]L-proline across the intestinal wall was used to measure functional change following irradiation of the exteriorized rat small intestine and to see whether an elemental amino acid diet would modify these changes. Segments (15 cm) of the exteriorized upper ileum of male Wistar rats were exposed to 1000 rad. Active transport against a concentration gradient of [ 3 H]L-proline from this irradiated segment was measured using the everted sac technique on days 1, 3, 7, 10, 14, 21, and 30 post-irradiation. Irradiated rats maintained on a normal diet showed depression of absorptive function with only partial recovery by day 30. Irradiated rats maintained on an elemental amino acid diet also showed an initial drop in function but then recovered absorptive function completely by day 7

  7. Glycosidic Bond Cleavage is Not Required for Phytosteryl Glycoside-Induced Reduction of Cholesterol Absorption in Mice

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Moreau, Robert A.

    2012-01-01

    Phytosteryl glycosides occur in natural foods but little is known about their metabolism and bioactivity. Purified acylated steryl glycosides (ASG) were compared with phytosteryl esters (PSE) in mice. Animals on a phytosterol-free diet received ASG or PSE by gavage in purified soybean oil along with tracers cholesterol-d7 and sitostanol-d4. In a three-day fecal recovery study, ASG reduced cholesterol absorption efficiency by 45 ± 6% compared with 40 ± 6% observed with PSE. Four hours after gavage, plasma and liver cholesterol-d7 levels were reduced 86% or more when ASG was present. Liver total phytosterols were unchanged after ASG administration but were significantly increased after PSE. After ASG treatment both ASG and deacylated steryl glycosides (SG) were found in the gut mucosa and lumen. ASG was quantitatively recovered from stool samples as SG. These results demonstrate that ASG reduces cholesterol absorption in mice as efficiently as PSE while having little systemic absorption itself. Cleavage of the glycosidic linkage is not required for biological activity of ASG. Phytosteryl glycosides should be included in measurements of bioactive phytosterols. PMID:21538209

  8. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Directory of Open Access Journals (Sweden)

    Rebecca M Heidker

    Full Text Available Bile acid (BA sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY. Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1, compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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. © 2015 Society for Endocrinology.

  11. Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats.

    Science.gov (United States)

    Zhang, Hailong; Huang, Xiaoyan; Zhang, Yongjing; Gao, Yang

    2017-03-01

    Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic. To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats. Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively. HP-β-CD-PEI polymers, especially HP-β-CD-PEI 1800 , demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI 1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects. HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

    Directory of Open Access Journals (Sweden)

    Senem Kamiloglu

    2015-09-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    Simko, V.; Kelley, R.E.

    1988-01-01

    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 14 C-triolein marker remained proportional to the load up to 2359 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 14 C-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. Excretion and intestinal absorption of tritiated glutamic acid by carp, Cyprinus Carpio

    International Nuclear Information System (INIS)

    Watabe, Terushia; Kistner, G.

    1986-01-01

    Excretion and intestinal absorption of tritiated glutamic acid by carp was investigated. Approximately 80% of orally administered tritium was excreted at a half life value of 1.4 h and an observed slower excretion of 7 days for the remainder. Tritium incorporated in glutamic acid was efficiently retained at the site of absorption, i.e. intestine, liver, gill, kidney, blood and muscle. A dual marking experiment using tritiated glutamic acid and 14 C-market glutamic acid showed higher excretion of tritium by factors 2.0 to 4.9 than that of 14 C. Tritiated glutamic acid is considered to be mainly incorporated in the citric acid cycle soon after administration and the release of tritium in tritiated water through the cycle is assumed as causing the initial rapid excretion of tritium in carp. The intestinal absorption of glutamic acid was likely to depend on its concentration in the administered solution. The maximum level of absorption is estimated to be 0.1 m mol/0.5 h for one year old carp. The results obtained here would make it possible to estimate the tritium contamination of fish due to tritiated glutamic acid entering the food chain. (orig.)

  17. [Effect of mazindol on glucose absorption in everted rat small intestine].

    Science.gov (United States)

    Tsuchiya, M; Inoue, S; Satta, M; Yoshimura, H; Arita, M; Takamura, Y

    1986-06-01

    Effect of an anorexiant, mazindol, on glucose absorption was investigated. Ten weeks-old female Sprague-Dawley rats were divided into mazindol treated (fed on powder diet containing 100 mg/kg of mazindol) and control groups. Four weeks later, experiments of continuous observation of glucose absorption and glucose transport were performed in each group using the everted sac method. During 180 min of continuous observation of glucose absorption, significantly lowered glucose concentrations of the serosal medium were observed in the mazindol treated group at oral and caudal ends of the upper, caudal end of the middle, and caudal ends of the lower small intestine, whereas no significant differences in glucose concentrations of the mucosal medium were observed between the two groups. After 60 min incubation for monitoring the glucose transport, significantly decreased glucose concentrations of serosal medium were observed in mazindol treated group at oral and caudal ends of the upper, caudal ends of the middle and caudal ends of the lower small intestine, whereas no significant differences in glucose concentrations of mucosal medium were observed. The results suggested that there is little effect on glucose absorption, but the metabolism of glucose or the remaining glucose in the small intestinal wall is increased by mazindol treatment.

  18. The effects of critical illness on intestinal glucose sensing, transporters, and absorption.

    Science.gov (United States)

    Deane, Adam M; Rayner, Chris K; Keeshan, Alex; Cvijanovic, Nada; Marino, Zelia; Nguyen, Nam Q; Chia, Bridgette; Summers, Matthew J; Sim, Jennifer A; van Beek, Theresia; Chapman, Marianne J; Horowitz, Michael; Young, Richard L

    2014-01-01

    Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice. Prospective observational study in humans and mice. ICU and university-affiliated research laboratory. Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied. Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection. Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p absorption, associated with reduced intestinal expression of glucose transporters (sodium-dependent glucose transporter-1 and glucose transporter-2) and sweet taste receptor transcripts

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

    Directory of Open Access Journals (Sweden)

    Kristina eSundell

    2012-09-01

    Full Text Available 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.

  20. Improvement of intestinal absorption of forsythoside A in weeping forsythia extract by various absorption enhancers based on tight junctions.

    Science.gov (United States)

    Zhou, Wei; Qin, Kun Ming; Shan, Jin Jun; Ju, Wen Zheng; Liu, Shi Jia; Cai, Bao Chang; Di, Liu Qing

    2012-12-15

    Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no

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

    Science.gov (United States)

    Serafin, J.A.

    1984-01-01

    1. 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.2. Bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards.3. Mallards absorbed less dieldrin and mercury than black-crowned night-herons.4. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards.5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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

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

    Science.gov (United States)

    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. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

    Science.gov (United States)

    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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans.

    Science.gov (United States)

    Chedik, Lisa; Mias-Lucquin, Dominique; Bruyere, Arnaud; Fardel, Olivier

    2017-06-30

    Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides ( n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines ( n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds ( n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.

  7. Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions.

    Science.gov (United States)

    Nicolas, Jean-Marie; Bouzom, François; Hugues, Chanteux; Ungell, Anna-Lena

    2017-04-01

    The dissolution, intestinal absorption and presystemic metabolism of a drug depend on its physicochemical characteristics but also on numerous physiological (e.g. gastrointestinal pH, volume, transit time, morphology) and biochemical factors (e.g. luminal enzymes and flora, intestinal wall enzymes and transporters). Over the past decade, evidence has accumulated indicating that these factors may differ in children and adults resulting in age-related changes in drug exposure and drug response. Thus, drug dosage may require adjustment for the pediatric population to ensure the desired therapeutic outcome and to avoid side-effects. Although tremendous progress has been made in understanding the effects of age on intestinal physiology and function, significant knowledge gaps remain. Studying and predicting pharmacokinetics in pediatric patients remains challenging due to ethical concerns associated with clinical trials in this vulnerable population, and because of the paucity of predictive in vitro and in vivo animal assays. This review details the current knowledge related to developmental changes determining intestinal drug absorption and pre-systemic metabolism. Supporting experimental approaches as well as physiologically based pharmacokinetic modeling are also discussed together with their limitations and challenges. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Lupin protein isolate versus casein modifies cholesterol excretion and mRNA expression of intestinal sterol transporters in a pig model.

    Science.gov (United States)

    Radtke, Juliane; Geissler, Stefanie; Schutkowski, Alexandra; Brandsch, Corinna; Kluge, Holger; Duranti, Marcello M; Keller, Sylvia; Jahreis, Gerhard; Hirche, Frank; Stangl, Gabriele I

    2014-02-03

    Lupin proteins exert hypocholesterolemic effects in man and animals, although the underlying mechanism remains uncertain. Herein we investigated whether lupin proteins compared to casein modulate sterol excretion and mRNA expression of intestinal sterol transporters by use of pigs as an animal model with similar lipid metabolism as humans, and cellular cholesterol-uptake by Caco-2 cells. Two groups of pigs were fed cholesterol-containing diets with either 230 g/kg of lupin protein isolate from L. angustifolius or 230 g/kg casein, for 4 weeks. Faeces were collected quantitatively over a 5 d period for analysis of neutral sterols and bile acids by gas chromatographically methods. The mRNA abundances of intestinal lipid transporters were analysed by real-time RT-PCR. Cholesterol-uptake studies were performed with Caco-2 cells that were incubated with lupin conglutin γ, phytate, ezetimibe or albumin in the presence of labelled [4-14C]-cholesterol. Pigs fed the lupin protein isolate revealed lower cholesterol concentrations in total plasma, LDL and HDL than pigs fed casein (P isolate compared to pigs that received casein (+57.1%; P isolate than in those who received casein (P isolate is attributable to an increased faecal output of cholesterol and a reduced intestinal uptake of cholesterol. The findings indicate phytate as a possible biofunctional ingredient of lupin protein isolate.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Relevance of interactions between sphingomyelin and cholesterol in biliary and intestinal tract

    NARCIS (Netherlands)

    van Erpecum, Karel J.; Petruzzelli, Michele; Groen, Albert K.; Moschetta, Antonio

    2007-01-01

    Phosphatidylcholine and sphingomyelin are the major phospholipids of the hepatocytic canalicular membrane outer leaflet. Sphingomyelin may preferentially reside with cholesterol in liquid-ordered domains. In contrast, phosphatidylcholine is the exclusive phospholipid secreted in rat bile (enriched

  11. Data for the size of cholesterol-fat micelles as a function of bile salt concentration and the physico-chemical properties of six liquid experimental pine-derived phytosterol formulations in a cholesterol-containing artificial intestine fluid

    Directory of Open Access Journals (Sweden)

    Jinsoo Yi

    2017-02-01

    Full Text Available The data in this paper are additional information to the research article entiltled “Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols” (Yi et al.,2016 [1]. The data derived from the measurement on six liquid formulations of commercial pine-derived phytosterol (CPP by dynamic light scattering. The data cover micelle size and the zeta-potential for formulations with cholesterol including monoglyceride, oleic acid, and bile salt. The data demonstrate the critical effect of the bile salt concentration on the size of cholesterol-digested fat micelles.

  12. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  13. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  14. Acupuncture Improves Intestinal Absorption of Iron in Iron-deficient Obese Patients: A Randomized Controlled Preliminary Trial

    Directory of Open Access Journals (Sweden)

    Xin-Cai Xie

    2017-01-01

    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 systemic leptin-hepcidin levels.

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

    Science.gov (United States)

    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 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Qin, Chaobin; Yang, Liping; Zheng, Wenjia; Yan, Xiao; Lu, Ronghua; Xie, Dizhi; Nie, Guoxing

    2018-01-08

    The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-01

    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.

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

    Science.gov (United States)

    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. Copyright © 2012 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Prediction of drug intestinal absorption in human using the Ussing chamber system: A comparison of intestinal tissues from animals and humans.

    Science.gov (United States)

    Miyake, Masateru; Koga, Toshihisa; Kondo, Satoshi; Yoda, Noriaki; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

    2017-01-01

    An adequate evaluation system for drug intestinal absorption is essential in the pharmaceutical industry. Previously, we established a novel prediction system of drug intestinal absorption in humans, using the mini-Ussing chamber equipped with human intestinal tissues. In this system, the TI value was defined as the sum of drug amounts transported to the basal-side component (X corr ) and drug amounts accumulated in the tissue (T corr ), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. In order to apply this system to the screening assay, it is important to understand the differences between animal and human tissues in the intestinal absorption of drugs. In this study, the transport index (TI) values of three drugs, with different levels of membrane permeability, were determined to evaluate the rank order of drug absorbability in intestinal tissues from rats, dogs, and monkeys. The TI values in small intestinal tissues in rats and dogs showed a good correlation with those in humans. On the other hand, the correlation of TI values in monkeys was lower compared to rats and dogs. The rank order of the correlation coefficient between human and investigated animal tissues was as follows: dog (r 2 =0.978), rat (r 2 =0.955), and monkey (r 2 =0.620). TI values in large intestinal tissues from rats (r 2 =0.929) and dogs (r 2 =0.808) also showed a good correlation. The obtained TI values in small intestinal tissues in rats and dogs were well correlated with the fraction of drug absorbed (F a ) in humans. From these results, the mini-Ussing chamber, equipped with intestinal tissues in rats and dogs, would be useful as a screening tool in the drug discovery stage. In addition, the obtained TI values can be used for the prediction of the F a in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments.

    Science.gov (United States)

    Da Silva, Laís Cristina; Da Silva, Taynara Lourenço; Antunes, Alisson Henrique; Rezende, Kênnia Rocha

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell™ inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; ×10(-6) cm/s) was determined for atenolol (10.7 ± 1.2), caffeine (17.6 ± 3.1), cimetidine (6.9 ± 0.1), metoprolol (12.6 ± 0.7), theophylline (15.3 ± 1.6) and, ranitidine (3.8 ± 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Dyslipidaemia--hepatic and intestinal cross-talk.

    LENUS (Irish Health Repository)

    Tomkin, Gerald H

    2010-06-01

    Cholesterol metabolism is tightly regulated with the majority of de novo cholesterol synthesis occurring in the liver and intestine. 3 Hydroxy-3-methylglutaryl coenzyme A reductase, a major enzyme involved in cholesterol synthesis, is raised in both liver and intestine in diabetic animals. Niemann PickC1-like1 protein regulates cholesterol absorption in the intestine and facilitates cholesterol transport through the liver. There is evidence to suggest that the effect of inhibition of Niemann PickC1-like1 lowers cholesterol through its effect not only in the intestine but also in the liver. ATP binding cassette proteins G5\\/G8 regulate cholesterol re-excretion in the intestine and in the liver, cholesterol excretion into the bile. Diabetes is associated with reduced ATP binding cassette protein G5\\/G8 expression in both the liver and intestine in animal models. Microsomal triglyceride transfer protein is central to the formation of the chylomicron in the intestine and VLDL in the liver. Microsomal triglyceride transfer protein mRNA is increased in diabetes in both the intestine and liver. Cross-talk between the intestine and liver is poorly documented in humans due to the difficulty in obtaining liver biopsies but animal studies are fairly consistent in showing relationships that explain in part mechanisms involved in cholesterol homeostasis.

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

    Science.gov (United States)

    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.

  5. The Relationship Between Intestinal Iron Absorption and Hepatic Parenchymal Cell Damage

    International Nuclear Information System (INIS)

    Kim, Mok Hyun; Hahn, Shin Suck

    1971-01-01

    Since the iron balance is maintained by regulated intestinal absorption rather than regulated excretion, there have been many reports concerning the factors which may influence the intestinal iron absorption. As the liver is the largest iron storage organ of the body, any hepatocellular damage may result in disturbances in iron metabolism, e,g., frequent co-existence of haemochromatosis and liver cirrhosis, or elevated serum iron level and increased iron absorption rate in patients with infectious hepatitis or cirrhosis. In one effort to demonstrate the influence of hepatocellular damage on intestinal iron absorption, the iron absorption rate was measured in the rabbits whose livers were injured by a single subcutaneous injection of carbon tetrachloride (doses ranging from 0.15 to 0.5 cc per kg of body weight) or by a single irradiation of 2, 000 to 16, 000 rads with Co on the liver locally. A single oral dose of 1μCi of Fe-citrate with 0.5 mg of ferrous citrate was fed in the fasting state, 24 hours after hepatic damage had been induced, without any reducing or chelating agents, and stool was collected for one week thereafter. Serum iron levels, together with conventional liver function teats, were measured at 24, 48, 72, 120 and 168 hours after liver damage had been induced. All animals were sacrificed upon the completing of the one week's test period and tissue specimens were prepared for H-E and Gomori's iron stain. Following are the results. 1. Normal iron absorption rate of the rabbit was 41.72±3.61% when 0.5 mg of iron was given in the fasting state, as measured by subtracting the amount recovered in stool collected for 7 days from the amount given. The test period of 7 days is adequate, for only 1% of the iron given was excreted thereafter. 2. The intestinal iron absorption rate and serum iron level were significantly increased when the animal was poisoned by a single subcutaneous injection of 0.15 cc, per kg. of body weight of carbon tetrachloride or

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

    International Nuclear Information System (INIS)

    Limsuwan, T.; Lovell, R.T.

    1981-01-01

    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

  7. Modulating effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies.

    Science.gov (United States)

    Shen, Qi; Li, Wenji; Lin, Yulian; Katsumi, Hidemasa; Okada, Naoki; Sakane, Toshiyasu; Fujita, Takuya; Yamamoto, Akira

    2008-12-01

    The effects of polyethylene glycol 20000 (PEG 20000) on the intestinal absorption of prednisolone, methylprednisolone and quinidine, three P-glycoprotein (P-gp) substrates, across the isolated rat intestinal membranes were examined by an in-vitro diffusion chamber system. The serosal-to-mucosal (secretory) transport of these P-gp substrates was greater than their mucosal-to-serosal (absorptive) transport, indicating that their net movement across the intestinal membranes was preferentially in the secretory direction. The polarized secretory transport of these drugs was remarkably diminished and their efflux ratios decreased in the presence of PEG 20000. In addition, PEG 20000 did not affect the transport of Lucifer yellow, a non-P-gp substrate. The intestinal membrane toxicity of PEG 20000 was evaluated by measuring the release of alkaline phosphatase (ALP) and protein from the intestinal membranes. The release of ALP and protein was enhanced in the presence of 20 mM sodium deoxycholate (NaDC), a positive control, while these biological parameters did not change in the presence of 0.1-5% (w/v) PEG 20000. These findings indicated that the intestinal membrane damage caused by PEG 20000 was not a main reason for the enhanced absorptive transport of these P-gp substrates in the presence of PEG 20000. Furthermore, the transepithelial electrical resistance (TEER) of rat jejunal membranes in the presence or absence of PEG 20000 was measured by a diffusion chamber method. PEG 20000 (0.1-5.0 % w/v) did not change the TEER values of the rat jejunal membranes, indicating that the increase in the absorptive transport of these P-gp substrates might not be due to the increased transport of these P-gp substrates via a paracellular pathway caused by PEG 20000. Finally, the effect of PEG 20000 on the intestinal absorption of quinidine was examined by an in-situ closed-loop method. The intestinal absorption of quinidine was significantly enhanced in the presence of 0.1-1.0% (w

  8. Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy.

    Science.gov (United States)

    Mori, Kenta; Ishida, Tatsuro; Tsuda, Shigeyasu; Oshita, Toshihiko; Shinohara, Masakazu; Hara, Tetsuya; Irino, Yasuhiro; Toh, Ryuji; Hirata, Ken-Ichi

    2017-02-01

    Clinical trials suggest that residual risks remain for coronary artery disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering therapy. We aimed to investigate the role of exogenous lipids in the prognosis of CAD after percutaneous coronary intervention (PCI). A total of 145 patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients were enrolled in this study. CAD patients underwent follow-up coronary angiography 6-9 months after PCI, and were classified into three groups: 1) patients who showed in-stent restenosis (ISR) in the original stented segment, 2) patients with other non-target coronary atherosclerotic lesions (de novo), and 3) patients with neither ISR nor a de novo lesion. Biochemical analyses were performed on fasting serum samples at the time of follow-up coronary angiography. Despite the controlled serum LDL-C levels, CAD patients with statin showed elevated cholesterol absorption marker campesterol/total cholesterol (TC), synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were associated with de novo lesion progression after PCI. In stepwise multivariate logistic regression analysis, campesterol/TC and apoB48 concentrations were independent risk factors for de novo lesion progression in statin-treated CAD patients after PCI. The increase of cholesterol absorption marker and apoB48 concentration may lead to the progression of de novo lesions, and these markers may represent a residual risk during statin treatment after PCI.

  9. Effects of Kluyveromyces marxianus Isolated from Tibetan Mushrooms on the Plasma Lipids, Egg Cholesterol Level, Egg Quality and Intestinal Health of Laying Hens

    Directory of Open Access Journals (Sweden)

    S Zhong

    Full Text Available ABSTRACT The effects of the Kluyveromyces marxianus M3 strain, isolated from Tibetan mushrooms, on plasma lipids, egg cholesterol level, egg quality, and intestinal health of laying hens were evaluated. In total, 160 Beijing fatty laying hens (43 weeks old were divided into four groups and fed a basal diet supplemented with 0%, 0.1%, 0.3%, or 0.5% freeze-dried K. marxianus M3 powder for four weeks. The results showed that yeast supplementation reduced serum total cholesterol (TC, triglyceride (TG, low density lipoprotein-cholesterol (LDL-C, and very low density lipoprotein-cholesterol (VLDL-C levels (p<0.01, and increased serum high density lipoprotein-cholesterol (HDL-C level (p<0.05. Moreover, regardless of K. marxianus M3 dietary addition level, the cholesterol content of the eggs decreased by more than 26%. When0.3% yeast was supplemented, significant differences were found in the egg weights, shell strength, albumen height, Haugh unit and nutrient content of the eggs (p<0.01. Finally, 0.3% yeast supplementation improved the intestinal flora conditions of the hens by decreasing the Salmonella and Staphylococcus aureus counts (p<0.01 and increasing the Bifidobacterium count (p<0.01. The results in this work demonstrated that yeast culture supplementation to the diets deceased the serum and egg yolk cholesterol, and increased egg quality.

  10. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    Science.gov (United States)

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. In vivo and in vitro evaluations of intestinal gabapentin absorption: effect of dose and inhibitors on carrier-mediated transport.

    Science.gov (United States)

    Larsen, Malte Selch; Frølund, Sidsel; Nøhr, Martha Kampp; Nielsen, Carsten Uhd; Garmer, Mats; Kreilgaard, Mads; Holm, René

    2015-03-01

    Gabapentin exhibits saturable absorption kinetics, however, it remains unclear which transporters that are involved in the intestinal transport of gabapentin. Thus, the aim of the current study was to explore the mechanistic influence of transporters on the intestinal absorption of gabapentin by both in vivo and in vitro investigations Pharmacokinetic parameters were determined following a range of intravenous (5-100 mg/kg) and oral doses (10-200 mg/kg) in rats. Transepithelial transport (50 μM-50 mM) and apical uptake of gabapentin (0.01-50 mM) were investigated in Caco-2 cells. The effect of co-application of the LAT-inhibitor, BCH, and the b(0,+)-substrate, L-lysine, on intestinal transport of gabapentin was evaluated in vivo and in vitro. Gabapentin showed dose-dependent oral absorption kinetics and dose-independent disposition kinetics. Co-application of BCH inhibited intestinal absorption in vivo and apical uptake in vitro, whereas no effect was observed following co-application of L-lysine. The present study shows for the first time that BCH was capable of inhibiting intestinal absorption of gabapentin in vivo. Furthermore, in Caco-2 cell experiments BCH inhibited apical uptake of gabapentin. These findings may imply that a BCH-sensitive transport-system was involved in the apical and possibly the basolateral transport of gabapentin across the intestinal wall.

  12. Intestinal Absorption and First-Pass Metabolism of Polyphenol Compounds in Rat and Their Transport Dynamics in Caco-2 Cells

    Science.gov (United States)

    Zhang, Feng; Huan, Menglei; Cao, Weidong; Li, Kangchu; Yang, Jingyue; Cao, Dayong; Zhou, Siyuan; Mei, Qibing

    2012-01-01

    Background Polyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and are therefore readily consumed by humans. The relationship between their chemical structure and intestinal absorption, transport, and first-pass metabolism remains unresolved, however. Methods Here, we investigated the intestinal absorption and first-pass metabolism of four polyphenol compounds, apigenin, resveratrol, emodin and chrysophanol, using the in vitro Caco-2 cell monolayer model system and in situ intestinal perfusion and in vivo pharmacokinetic studies in rats, so as to better understand the relationship between the chemical structure and biological fate of the dietary polyphenols. Conclusion After oral administration, emodin and chrysophanol exhibited different absorptive and metabolic behaviours compared to apigenin and resveratrol. The differences in their chemical structures presumably resulted in differing affinities for drug-metabolizing enzymes, such as glucuronidase and sulphatase, and transporters, such as MRP2, SGLT1, and P-glycoprotein, which are found in intestinal epithelial cells. PMID:22253753

  13. Intestinal absorption and excretion of thallium (201Tl) in the rat.

    Science.gov (United States)

    Sabbioni, E; Di Nucci, A; Edel, J; Gregotti, C; Marafante, E; Manzo, L

    1984-01-01

    The gastrointestinal transport of 201Tl-labelled monovalent thallium has been studied in normal and rats with cannulated bile ducts using an in vivo ligated loop technique. A marked difference in the Tl absorptive capacity among the various sections of the gut was observed. 201Tl was taken up more quickly from the colon than from any other segment and the uptake from the ileum and jejunum was higher than from the stomach. In addition, considerable amounts of the intravenously administered thallium were excreted into the intestinal lumen. The biliary excretion was very low compared with the direct transfer of 201Tl across the gastrointestinal wall that occurred against a tissue-to-plasma concentration gradient. In the rat, the large intestine seems to be the major area for the enteral reabsorption and recycling of thallium (I) ions.

  14. Intestinal absorption and distribution of 14C-palmitic acid in an young Indian freshwater major carp, Labeo rohita (Hamilton)

    International Nuclear Information System (INIS)

    Sinha, G.M.; Chakrabarti, P.

    1983-01-01

    The mechanism of absorption and distribution of radioactive lipids in the various regions of the intestine and hepatopancreas of young Labeo rohita (Ham.) was investigated after feeding with small-sized earthworms (Pheretima posthuma), preinjected with 14 C-Palmitic acid. Dietary free fatty acids were mainly absorbed in the various regions (anterior, middle and posterior) of the intestine-the absorption capacity, however, varying greatly from region to region. The absorption of free fatty acids through the luminal brush border of the various regions of the intestine started at 24 hr of post-feeding (h.p.f.) with labelled diet and recorded its peak during 32 +- 2 h.p.f. However, middle intestine was found to be more active for such absorption than the other two regions (anterior and posterior). Incorporation of labelled Palmitic acid in the columnar epithelial cells and its subsequent transportation in the hepatic tissues, via lymphatic systems took place with in a short interval after absorption. However, absorption was completed within 40 h.p.f. when deposition of radioactive lipids was found to be maximum in the columnar epithelial cells of the various regions of the intestine and hepatic tissues. (author)

  15. Non-starch polysaccharides extracted from seaweed can modulate intestinal absorption of glucose and insulin response in the pig.

    Science.gov (United States)

    Vaugelade, P; Hoebler, C; Bernard, F; Guillon, F; Lahaye, M; Duee, P H; Darcy-Vrillon, B

    2000-01-01

    We have investigated the possible effects of algal polysaccharides on postprandial blood glucose and insulin responses in an animal model, the pig. Three seaweed fibres of different viscosities, extracted from Palmaria palmata (PP), Eucheuma cottonii (EC), or Laminaria digitata (LD), were compared to purified cellulose (CEL). Blood glucose and plasma insulin levels were monitored and intestinal absorption quantified for 8 h following a high carbohydrate test-meal supplemented with 5% fibre. Digestive contents were also sampled, 5 h postprandial. As compared to CEL, PP had no effect on glucose and insulin responses. The latter decreased with EC, but glucose absorption balance was not modified. LD addition resulted in a dramatically reduced glucose absorption balance, accompanied by a higher amount of starch left in the small intestine. Among polysaccharides tested, only the highly viscous alginates could affect intestinal absorption of glucose and insulin response.

  16. An ATPase dependent, radiosensitive acidic microclimate essential for intestinal folate absorption

    International Nuclear Information System (INIS)

    Kesavan, V.; Noronha, J.M.

    1978-01-01

    Methyltetrahydrofolic acid transport was studied across everted sacs of rat jejunal segments from control and whole-body X-irradiated (700 rad) rats at 10 -5 M concentrations (at which optimum transport occurs) at various pHs. The folate transport from mucosal to serosal compartment was inhibited by about 55% in irradiated rats at the pH of the intestinal chyme (6.5). Extraneous ATP in the incubation system could restore the defective transport of the irradiated intestine. The maximum folate transport which occurred at pH 4.0 was not adversely affected by whole body irradiation. An acidic, pH dependent, passive uptake of 5-methyltetrahydrofolic acid was observed. The normal absorption barrier of the small bowel was not disrupted by the acidification process as practically no uptake was observed with irradiated segments pretreated at pH 4.0 except in the presence of ATP. Leucine and serine transport at a zero concentration gradient indicated active transport mechanisms which were not affected by acidification. Their uptake was additively increased in the presence of glucose and ATP, further indicating that the normal physiology of the intestines was not affected by the acidification process. An intestinal mucosal cell surface ATPase was observed which was Mg 2+ dependent. It could hydrolyse solution phase ATP and thus generate the protons necessary for the acidification of a microenvironment where passive uptake of the neutral folate species could occur. The ATPase activity was inhibited about 90% by 50 mM-Na azide at pH 6.5. Below this concentration folate transport was also inhibited. Na azide did not inhibit folate transport at pH 4.0, suggesting that its inhibition of folate uptake at pH 6.5 is related to its inhibitory effect on ATPase, rather than on folate transport per se. ATPase activity was therefore essential for folate transport at the pH of the intestinal chyme. (author)

  17. Studies on the in vitro absorption of spice principles--curcumin, capsaicin and piperine in rat intestines.

    Science.gov (United States)

    Suresh, D; Srinivasan, K

    2007-08-01

    A comparative evaluation of the absorbability of three structurally similar and physiologically active spice principles in an in vitro system consisting of everted rat intestinal sacs was made. When everted sacs of rat intestines were incubated with 50-1000 microg of curcumin in 10 ml incubation medium, absorption of the spice principle was maximum at 100 microg concentration. The amount of absorbed curcumin present in the serosal fluid was negligible. This and the comparatively lower recovery of the original compound suggested that curcumin to some extent undergoes a modification during absorption. For similar concentrations of added piperine, about 44-63% of piperine disappeared from the mucosal side. Absorption of piperine which was maximum at 800 microg per 10 ml was about 63%. The absolute amounts of piperine absorbed in this in vitro system exceeded the amounts of curcumin. The absorbed piperine could be traced in both the serosal fluid and in the intestinal tissue, indicating that piperine did not undergo any metabolic change during the process of absorption. 7-12% of the absorbed piperine was found in the serosal fluid. When everted sacs of rat intestines were incubated with 10-500 microg of capsaicin, a maximum of 82-88% absorption could be seen in the lower concentrations, and the amount of absorbed capsaicin did not proportionately increase at higher concentrations. A relatively higher percentage of the absorbed capsaicin could be seen in the serosal fluid as compared to curcumin or piperine. When these spice active principles were associated with mixed micelles, their in vitro intestinal absorption was relatively higher. Curcumin absorption in everted intestinal sac increased from 48.7% to 56.1% when the same was present in micelles. In the case of capsaicin and piperine, increase in absorption was 27.8-44.4% and 43.4-57.4%, respectively, when they were present in micelles as compared to its native form.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  20. Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical preparation.

    Science.gov (United States)

    Werner, E; Hansen, Ch; Roth, P; Kaltwasser, J P

    1999-01-01

    Only few data are available on intestinal calcium absorption from foodstuffs and composite meals in humans. The aim of the study was to compare intraindividually the calcium absorption from milk and from a breakfast with that from a pharmaceutical calcium preparation of equal calcium content. In 8 healthy volunteers between 44 and 58 years of age, the intestinal calcium absorption was measured in randomized order applying the double isotope technique from: (1) 500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg 42Ca in a sterile isotonic solution were injected intravenously. The mean values of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and 28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The data show that less calcium is absorbed from foodstuffs as compared to a preparation of optimal bioavailability. But in this study only the difference between absorption from the milk and from the meal was statistically significant. Therefore, it is possible to obtain a sufficient calcium supply of the human body also by properly selected foodstuffs.

  1. Serum plant sterols, cholestanol, and cholesterol precursors associate with histological liver injury in pediatric onset intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Nissinen, Markku J; Lohi, Jouko; Heikkilä, Päivi; Gylling, Helena; Pakarinen, Mikko P

    2014-10-01

    Increased serum concentrations of plant sterols, including stigmasterol, during parenteral nutrition (PN) have been linked with serum biochemical signs of intestinal failure-associated liver disease (IFALD), whereas clinical data on their correlation to histologic liver injury have been limited. We studied interrelations between serum noncholesterol sterols and histologic liver injury in pediatric-onset intestinal failure (IF). Serum plant sterols (stigmasterol, avenasterol, sitosterol, and campesterol), cholestanol, and cholesterol precursors (cholestenol, lathosterol, and desmosterol) were measured in 50 IF patients at a median age 7.3 y and in 86 matched controls. Forty patients underwent liver biopsies. Sixteen patients had been receiving PN for 45 mo, and 34 patients had received PN for 9.1 mo but had not received PN for 5.4 y. Serum plant sterols were higher in patients who were currently receiving PN than in controls and were related to conjugated bilirubin (r = 0.799-0.541, P 2-fold higher in patients with persistent liver steatosis than in those without steatosis or controls (P liver steatosis after weaning off PN. Serum cholestanol reflects liver injury in IF patients. © 2014 American Society for Nutrition.

  2. Evaluation of intestinal absorption of amtolmetin guacyl in rats: breast cancer resistant protein as a primary barrier of oral bioavailability.

    Science.gov (United States)

    Rong, Zhihui; Xu, Yanjiao; Zhang, Chengliang; Xiang, Daochun; Li, Xiping; Liu, Dong

    2013-02-27

    The purpose of the present study was to investigate the role of efflux transporters on the intestinal absorption of amtolmetin guacyl (MED-15). The effects of P-glycoprotein (P-gp), multiple resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on intestinal absorption amount of MED-5 (tolmetin-glycine amide derivative), the metabolite formed from MED-15 in the intestinal epithelial cells were studied in the in vitro everted gut sac experiments. Moreover, the in situ single-pass intestine perfusion was adopted to clarify the role of efflux transporters in excreting MED-5 in knockout mice. The plasma concentration of MED-5 and tolmetin, the metabolite formed from MED-5 was determined in Bcrp1 knockout mice and wild-type mice. BCRP inhibitor Ko143 (50 μM and 100 μM) significantly increased the intestinal absorption amount in jejunum, ileum and colon (pintestinal segment. Furthermore, the plasma concentration MED-5 and tolmetin, metabolites of MED-15, increased 2-fold and 4-fold, respectively, in Bcrp1 knockout mice compared with wild-type mice after the single-pass perfusion of small intestine with MED-15. It may be concluded that BCRP plays an important role in the intestinal efflux of MED-5 and limits the bioavailability after oral administration of MED-15. Copyright © 2013. Published by Elsevier Inc.

  3. In Vitro Intestinal Absorption and Metabolism of Magnoflorine and its Potential Interaction in Coptidis Rhizoma Decoction in Rat.

    Science.gov (United States)

    Xue, Baojuan; Zhao, Yuanyuan; Su, Jin; Miao, Qing; Miao, Peipei; Chen, Ning; Wang, Zijian; Zhang, Yujie; Ma, Shuangcheng

    2017-04-01

    In our previous studies, it was found that there existed pharmacokinetic interactions between magnoflorine and the rest of the ingredients in Coptidis Rhizoma. In this study, the pharmacokinetic interaction mechanism of magnoflorine with the rest of the components in Coptidis Rhizoma was researched based on the intestinal absorption and metabolism characteristics. The absorption characteristics of magnoflorine in each rat intestinal segments were evaluated by non-everted intestinal sac model. To identify the metabolites of magnoflorine, the acceptor solutions of each intestinal segment at 120 min were analyzed by HPLC-LTQ-Orbitrap MS. The accumulative absorption (Q), the absorption rate (J) and the apparent permeability coefficient (P app ) of magnoflorine were increased in duodenum, jejunum, ileum and colon of the Coptidis Rhizoma group as compared to the magnoflorine group, but there was no statistical difference between the two groups (P > 0.05). Four phase I metabolites of magnoflorine were identified in intestinal acceptor solutions of pure compound, while eight metabolites were detected in that of Coptidis Rhizoma decoction including six phase I metabolites and two phase II metabolic products. It was shown that the rest of the ingredients in Coptidis Rhizoma accelerated the absorption of magnoflorine weakly and promoted the metabolism of magnoflorine in the gut. The effects of other processes in the pharmacokinetics should be further evaluated.

  4. Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota.

    Science.gov (United States)

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

    2015-12-01

    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 (NEC) and sepsis, and the influence of HMOs on the microbiota is unclear. 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 to complement a previous analysis. 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 nonsecretor mothers. Specific HMO structures in the milk, urine, and feces were associated with alterations in fecal Proteobacteria and Firmicutes. 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 NEC, while other HMOs may increase dysbiosis in this population.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells.

    Science.gov (United States)

    Saito, Kei; Fujiwara, Tohru; Ota, Urara; Hatta, Shunsuke; Ichikawa, Satoshi; Kobayashi, Masahiro; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizuka, Masahiro; Tanaka, Tohru; Harigae, Hideo

    2017-09-01

    5-Aminolevulinic acid (ALA) is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC) for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN . The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1), as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

  8. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Kei Saito

    2017-09-01

    Full Text Available 5-Aminolevulinic acid (ALA is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN. The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1, as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

  9. Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine 210Pb and 59Fe absorption in duodenum and ileum in vivo

    International Nuclear Information System (INIS)

    Elsenhans, Bernd; Janser, Heinz; Windisch, Wilhelm; Schuemann, Klaus

    2011-01-01

    Highlights: → Absorption of 210 Pb increases much less than that of 59 Fe in murine duodena. → 210 Pb-absorption is almost equally high in murine duodenal and ileal segments. → 59 Fe absorption is much lower in ileal than in duodenal segments. → There must be an additional DMT1-independet pathway for intestinal Pb absorption. -- Abstract: Background: Human isotope studies and epidemiological trials are controversial as to whether lead absorption shares the absorptive pathways of iron and whether body lead content can be reduced by iron supplementation. Aim: To compare the impact of iron-deficiency on 59 Fe- and 210 Pb-absorption rates in duodenal and ileal segments. Methods: 59 Fe- and 210 Pb-absorption was determined in ligated duodenal and ileal segments from juvenile and adult iron-deficient and iron-adequate C57Bl6 wild-type mice (n = 6) in vivo at luminal concentrations corresponding to human exposure (Fe: 1 and 100 μmol/L; Pb: 1 μmol/L). Results and discussion: 59 Fe-absorption increased 10-15-fold in iron-deficient duodena from adult and adolescent mice. Ileal 59 Fe-absorption was 4-6 times lower than in iron-adequate duodena showing no adaptation to iron-deficiency. This in accordance to expectation as the divalent metal transport 1 (DMT1) shows low ileal expression levels. Juvenile 59 Fe-absorption was about twice as high as in adult mice. In contrast, duodenal 210 Pb-absorption was increased only 1.5-1.8-fold in iron-deficiency in juvenile and adult mice and, again in contrast to 59 Fe, ileal 210 Pb-absorption was as high as in iron-adequate duodena. Conclusions: The findings suggest a DMT1-independent pathway to mediate lead absorption along the entire small intestine in addition to DMT1-mediated duodenal uptake. Ileal lead absorption appears substantial, due the much longer residence of ingesta in the distal small intestine. Differences in lead-solubility and -binding to luminal ligands can, thus, explain the conflicting findings regarding the

  10. Absorption characteristics of the total alkaloids from Mahonia bealei in an in situ single-pass intestinal perfusion assay.

    Science.gov (United States)

    Sun, Yu-He; He, Xin; Yang, Xiao-Lin; Dong, Cui-Lan; Zhang, Chun-Feng; Song, Zi-Jing; Lu, Ming-Xing; Yang, Zhong-Lin; Li, Ping

    2014-07-01

    To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis (TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. The absorption behavior was investigated in an in situ single-pass intestinal perfusion (SPIP) assay in rats. The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds (jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids (borneol or camphor) was higher than by the monocyclic monoterpenes (menthol or menthone), and promotion by compounds with a hydroxyl group (borneol or menthol) was higher than those with a carbonyl group (camphor or menthone). The apparent permeability coefficient (Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant (Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein (P-gp) and organic cation transporters (OCT), rather than multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  11. Increased in situ intestinal absorption of phytoestrogenic diarylheptanoids from Curcuma comosa in nanoemulsions.

    Science.gov (United States)

    Su, Jian; Sripanidkulchai, Kittisak; Hu, Ying; Chaiittianan, Rungsiri; Sripanidkulchai, Bungorn

    2013-09-01

    Curcuma comosa has long been used as a gynecological medicine. Several diarylheptanoids have been purified from this plant, and their pharmacological effects were proven. However, there is no information about the absorption of C. comosa components to support the formulation usage. In the present study, C. comosa hexane extract and the mixture of its two major compounds, (4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol (DA1) and (6E)-1,7-diphenylhept-6-en-3-ol (DA2), were formulated into nanoemulsions. The physical properties of the nanoemulsions and the in situ intestinal absorptions of DA1 and DA2 were evaluated. The results demonstrated the mean particle sizes at 0.207 ± 0.001 and 0.408 ± 0.014 μm, and the zeta potential at -14.57 ± 0.85 and -10.47 ± 0.32 mV for C. comosa nanoemulsion (C.c-Nano) and mixture of diarlylheptanoid nanoemulsions (DA-Nano), respectively. The entrapments of DA1 and DA2 were 76.61% and 75.41%, and 71.91% and 71.63% for C.c-Nano and DA-Nano, respectively. The drug loading ratios of DA1 and DA2 were 351.47 and 614.53 μg/mg, and 59.48 and 126.72 μg/mg for C.c-Nano and DA-Nano. The intestinal absorption rates of DA1 and DA2 were 0.329 ± 0.015 and 0.519 ± 0.026 μg/min/cm2 in C.c-Nano, and 0.380 ± 0.006 and 0.428 ± 0.036 μg/min/cm2 in DA-Nano, which were five to ten times faster than those in oil. In conclusion, the formulation in nanoemulsion forms obviously increased the intestinal absorption rate of diarylheptanoids.

  12. Investigation of the effective components of the flowers of Trollius chinensis from the perspectives of intestinal bacterial transformation and intestinal absorption.

    Science.gov (United States)

    Guo, Lina; Qiao, Shanshan; Hu, Junhong; Li, Deli; Zheng, Shiqi; Shi, Duozhi; Liu, Junxiu; Wang, Rufeng

    2017-12-01

    The flowers of Trollius chinensis Bunge (Ranunculaceae), used for respiratory tract infections, mainly contain flavonoids, phenolic acids, and alkaloids; however, the effective components are debatable because of their unclear in vivo activities. This study investigates the effective components from the perspectives of biotransformation and absorption. Both single person derived- and multiple people-derived intestinal florae were used to investigate the biotransformation of aqueous extract of the flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0 mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2) monolayers and everted gut sacs were employed to evaluate the intestinal absorption of the intestinal bacterial transformed AEOF at the concentrations of 10, 20, and 30 mg/mL, respectively, for 180 min. 2″-O-β-l-Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid, proglobeflowery acid, and trolline in AEOF were not transformed by intestinal bacteria, while isoquercetin and trollioside were completely transformed. The P app values of 2″-O-β-l-galactopyranosylorientin, orientin, and vitexin calculated based on the experimental data of intestinal absorption were at the levels of 10 -5 , whereas those of veratric acid, proglobeflowery acid, and trolline were at 10 -4 . The mass ratio of flavonoids to phenolic acids to alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. The dominant position of flavonoids was replaced by phenolic acids after absorption. In addition to flavonoids which are usually considered as the dominant effective ones, phenolic acids and alkaloids should be also very important for the efficacy of these flowers.

  13. Enhanced Oral Delivery of Bisphosphonate by Novel Absorption Enhancers: Improvement of Intestinal Absorption of Alendronate by N-Acyl Amino Acids and N-Acyl Taurates and Their Absorption-Enhancing Mechanisms.

    Science.gov (United States)

    Nakaya, Yuka; Takaya, Mayu; Hinatsu, Yuta; Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-12-01

    Bisphosphonates (BPs) are carbon-substituted pyrophosphate analogs that exhibit a high affinity to hydroxyapatite and specifically inhibit bone resorption. Alendronate sodium (sodium 4-amino-1-hydroxybutylidene-1,1-bisphosphonate trihydrate) is a typical BP compound in clinical use. BPs have very low bioavailability, typically intestinal absorption is further reduced by co-administered drugs or food. In this study, we examined the effects of N-acyl amino acids and N-acyl taurates on the small intestinal absorption of alendronate. All N-acyl amino acids and N-acyl taurates increased the small intestinal absorption of alendronate, especially 1% (wt/vol) sodium palmitoyl sarcosinate (PN), which elicited a 14-fold increase. In addition, the absorption-enhancing effects of these enhancers were reversible and they may not cause continuous and irreversible membrane toxicity in the rat small intestine. Furthermore, we examined the absorption-promoting mechanisms of PN and found that it increased the membrane fluidity of the lipid bilayers. In addition, it was found that PN may open the tight junctions by reducing the expression level of claudin-4, which is a major tight junction protein. These findings indicate that these enhancers are useful for promoting the intestinal absorption of alendronate. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1983-01-01

    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)

  15. Intestinal absorption differences of major bioactive compounds of Gegenqinlian Decoction between normal and bacterial diarrheal mini-pigs in vitro and in situ.

    Science.gov (United States)

    Ling, Xiao; Xiang, Yuqiang; Chen, Feilong; Tang, Qingfa; Zhang, Wei; Tan, Xiaomei

    2018-04-15

    Intestinal condition plays an important role in drug absorption and metabolism, thus the effects of varied gastrointestinal diseases such as infectious diarrhea on the intestinal function are crucial for drug absorption. However, due to the lack of suitable models, the differences of absorption and metabolism of drugs between the diarrheal and normal intestines are rarely reported. Thus, in this study, Escherichia coli diarrhea model was induced in mini-pigs and single-pass intestinal perfusion and intestinal mucosal enzyme metabolism experiments were conducted. A simple and rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine the concentrations of 9 major components in Gegen Qinlian decoction (GQD). Samples were pretreated by protein precipitation with methanol and naringin and prednisolone were used as internal standards. The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 9 compounds. Results of intestinal perfusion showed that puerarin, daidzein, daidzin and baicalin and berberine were absorbed faster in diarrheal jejunum than in normal intestines (p intestine after incubation compared with the normal group (p absorption and metabolism of GQD were significantly different between the diarrheal and normal intestines, which suggest that bacterial diarrheal mini-pigs model can be used in the intestinal absorption study and is worthy to be applied in the other intestinal absorption study of anti- diarrheal drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  17. Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, James G.

    2017-11-01

    Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

  18. Effect of plant sterol-enriched diets on plasma and egg yolk cholesterol concentrations and cholesterol metabolism in laying hens.

    Science.gov (United States)

    Liu, X; Zhao, H L; Thiessen, S; House, J D; Jones, P J H

    2010-02-01

    Egg exists as a major dietary source of cholesterol in Western diets. In North America, laying hen diets are usually devoid of cholesterol when diets are formulated to exclude animal-based products. Hence, laying hens meet their physiological cholesterol requirement through de novo synthesis. Plant sterols exert a cholesterol-lowering effect in humans by interfering with intestinal sterol absorption. However, it is unknown whether plant sterol supplementation could be effective in reducing intestinal reabsorption of biliary cholesterol in laying hens, thus modulating whole body cholesterol in favor of lower plasma and yolk cholesterol content. The current study was designed to investigate the effect of diets enriched with 0, 0.5, 1, and 2% plant sterols on cholesterol absorption, synthesis, as well as plasma, liver, and egg yolk cholesterol concentrations in laying hens. After 8 wk of plant sterol intervention (first 2 wk were acclimatization), feed intake, BW, egg weight, egg yolk weight, egg production, Haugh units, liver mass, plasma, and hepatic cholesterol concentrations did not differ as a function of plant sterol supplementation. Egg cholesterol concentrations (mg/g) fluctuated during the 6-wk experimental period. At wk 6, a minor reduction in egg yolk cholesterol concentration (mg per g of yolk, Pcholesterol-enriched diets, respectively. However, such result failed to affect total egg cholesterol content. No statistical difference was observed across treatments over 6 wk. Neither cholesterol absorption rates nor synthesis differed as a function of treatment. Results suggested that overall cholesterol content in egg yolk was not affected by feeding hens plant sterol-enriched diets over 6 wk.

  19. Gas chromatography analysis of serum cholesterol synthesis and absorption markers used to predict the efficacy of simvastatin in patients with coronary heart disease.

    Science.gov (United States)

    Wu, Wen-Feng; Wang, Qi-Hui; Zhang, Tao; Mi, Shu-Hua; Liu, Yang; Wang, Lv-Ya

    2013-08-01

    We investigated the changes in cholesterol absorption and synthesis markers before and after simvastatin therapy in Chinese patients with coronary heart disease. We developed a gas chromatography method to identify cholesterol synthesis and absorption markers and measured them in patients with coronary heart disease. We then tested their use in predicting the efficacy of simvastatin in lowering cholesterol. Serum samples from 45 patients and 38 healthy humans (controls) were analyzed in a gas chromatography-flame ionization detector. Squalene and five non-cholesterol sterols--desmosterol and lathosterol (synthesis markers) and campesterol, stigmasterol, and sitosterol (absorption markers)--were detected. The recovery rates of the markers were 95-102%. After simvastatin treatment for four weeks, the total cholesterol and low-density lipoprotein cholesterol levels had significantly decreased from the baseline values (pmarkers and can be used to predict the efficacy of simvastatin in patients with coronary heart disease. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  1. 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.

    Science.gov (United States)

    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. Copyright 2009 Elsevier B.V. All rights reserved.

  2. Intestinal absorption of radiocalcium. Measurement by the oral and intraveinous activity ratio and by the inverse convolution method

    International Nuclear Information System (INIS)

    Monnier, L.; Collet, H.; Suquet, P.; Mirouze, J.

    1975-01-01

    The intestinal absorption of calcium was measured by a double isotopic labelling method, the results being obtained by a mathematical deconvolution technique. This analytical method was compared with the simple measurement of the plasma radioactivity ratio for the two isotopes administered orally and intraveinously respectively. The study covered 29 determinations. It was possible to estimate the total fractional absorption of calcium (TFACa) by calculating the average of the 47 Ca/ 45 Ca quotients measured on the 3rd and 8th hour after simultaneous administration of 45 Ca intraveinously and 47 Ca by mouth. The advantages of this method are obvious: need for only two blood samplings, simplicity of calculations which nevertheless give TFACa values comparable to those obtained by deconvolution analysis. However the only information supplied by the quotients method is the total fractional absorption, whereas inverse convolution analysis provides several interesting parameters such as the maximum absorption and the mean transit time of radiocalcium through the intestinal wall [fr

  3. Inhibition of intestinal radiocaesium absorption from Chernobyl contaminated whey by hexacyanoferrates(II) in pigs

    International Nuclear Information System (INIS)

    Dresow, B.; Asmus, J.; Fischer, R.; Nielsen, P.; Heinrich, H.C.

    1993-01-01

    The inhibition of radiocaesium transfer from Chernobyl contaminated whey powder to the pork and liver of fattening pigs using various dosages of different hexacyanoferrate (II) compounds (HCF) was studied under normal feeding conditions. Increasing amounts of all three hexacyanoferates tested resulted in a dose-dependent reduction in the 134+137 Cs activity concentration in all of the tissues sampled. KFe[Fe(CN) 6 ] and NE 4 Fe(CN) 6 ] were effective to the same extent while Fe 4 [Fe(CN) 6 ] 3 was less effective at dosages of 1-3 g d -1 HCF. Administration of 10 g d -1 HCF resulted in an almost complete inhibition (>99%) of intestinal radiocaesium absorption for all three compounds. (Author)

  4. Intestinal absorption of amino acids in the Pacific bluefin tuna (Thunnus orientalis): in vitro lysine-arginine interaction using the everted intestine system.

    Science.gov (United States)

    Martínez-Montaño, Emmanuel; Peña, Emyr; Viana, María Teresa

    2013-04-01

    The interaction between lysine (Lys) and arginine (Arg) in the proximal intestinal region of Pacific bluefin tuna (Thunnus orientalis) was evaluated using the everted intestine method. This in vitro intestinal system has been shown to be an effective tool for studying the nutrient absorption without the need to handle the tuna fish in marine cages as needed for digestibility and amino acid (AA) absorption. We used a factorial design with two sets of variables: low and high Lys concentration (10 and 75 mM) and four different Arg concentrations (3, 10, 20, and 30 mM). Both amino acids were dissolved in marine Ringer solution with a basal amino acidic composition consisting of a tryptone solution (9 mg mL(-1)). No interaction was observed between the absorption of Lys and Arg during the first 10 min of the experiment when low concentration of Lys and Arg was used in the hydrolyzate solution. However, there seemed to be a positive effect on Lys absorption when both amino acids were at high concentrations (30 and 75 mM, respectively). This type of studies will led us to test different formulations and/or additives to better understand the efficiency of AA supplementation as an alternative to in situ studies that are difficult to follow to design with the Pacific Bluefin Tuna.

  5. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

    Directory of Open Access Journals (Sweden)

    Courtney B. Ferrebee

    2015-03-01

    Full Text Available The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR and the G-protein-coupled bile acid receptor (TGR5.

  6. Absorption of cholesterol and β-sitosterol from cigarette smoke in Macaca mulatta

    International Nuclear Information System (INIS)

    Malinow, M.R.; McLaughlin, Phyllis; Aigner-Held, Rosemarie; Upson, Barbara; Isabelle, L.M.; Connor, W.E.; Lin, Don

    1986-01-01

    When smoke from single cigarettes containing (4- 14 C) chloresterol or β-(4- 14 C) sitosterol was delivered to the lungs of Rhesus macaques, plasma contained radiolabeled sterols up to 50 days later. Since chloresterol, as well as plant sterols (campesterol, stigmasterol and β-sitosterol), are normally present in cigarette smoke, our observations suggest that protracted absorption of sterols occurs after cigarette smoking. (author)

  7. [Comparative study on absorption kinetics in intestines of rats of epimedii foliunm of Xianlinggubao capsules prepared by different processes].

    Science.gov (United States)

    Wu, Huichao; Lu, Yang; Du, Shouying; Chen, Wen; Wang, Yue

    2011-10-01

    To study the characteristics of intestinal absorption of icariin and epimedin C of Xianlinggubao capsules, and compare the absorption of Xianlinggubao capsules prepared by different processes. Non everted gut sac method was applied to investigate the influence of absorption sites and concentration on icariin and epimedin C, which were determined by HPLC. The absorption rate constants of epimedin C in duodenum were absolutely more than that in jejunum and ileum (P absorption rate constants of icariin in jejunum were absolutely less than that in duodenum and ileum (P absorption rate constants of epimedin C and icariin kept at the same level when the concentrations of drug solution were at high, middle and low level. The Ka of epimedin C at three levels were 0.040, 0.058, 0.061 h(-1) , respectively, and the Ka of icariin at three levels were 0.002, 0.007, 0.003 h(-1), respectively. Intestinal absorption of icariin and epimedin C is not effected by concentrations. The absorption rate constants of icariin and epimedin C in new Xianlinggubao capsules are higher.

  8. Water absorption enhances the uptake of mannitol and decreases Cr-EDTA/mannitol permeability ratios in cat small intestine in situ

    NARCIS (Netherlands)

    Bijlsma, P. B.; Fihn, B. M.; Sjöqvist, A.; Groot, J. A.; Taminiau, J. A. J. M.; Jodal, M.

    2002-01-01

    Background: Recently, we hypothesized that mannitol absorption in human intestinal permeability tests is a reflection of small intestinal water absorption and is dependent mainly on the efficiency of the countercurrent multiplier in the villi. This may affect the outcome of clinical double-sugar

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

    Science.gov (United States)

    Balay, Kimberly S; Hawthorne, Keli M; Hicks, Penni D; Chen, Zhensheng; Griffin, Ian J; Abrams, Steven A

    2012-09-01

    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 stable isotope technique at two different time points when possible. The first study was conducted when the subject was receiving maximal tolerated feeds enterally while the ostomy remained in place. A second study was performed as soon as feasible after full feeds were achieved after intestinal repair. We found biochemical evidence of deficiencies of both zinc and copper in infants with small intestinal ostomies at both time points. Fractional zinc absorption with an ostomy in place was 10.9% ± 5.3%. After reanastamosis, fractional zinc absorption was 9.4% ± 5.7%. Net zinc balance was negative prior to reanastamosis. In conclusion, our data demonstrate that infants with a jejunostomy or ileostomy are at high risk for zinc and copper deficiency before and after intestinal reanastamosis. Additional supplementation, especially of zinc, should be considered during this time period.

  10. Effect of Cryptosporidium parvum infection on the absorptive capacity and paracellular permeability of the small intestine in neonatal calves

    Czech Academy of Sciences Publication Activity Database

    Klein, P.; Kleinová, T.; Volek, Z.; Šimůnek, Jiří

    2008-01-01

    Roč. 152, 1-2 (2008), s. 53-59 ISSN 0304-4017 Institutional research plan: CEZ:AV0Z50450515 Keywords : calves * cryptosporidium parvum * intestinal absorption Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.039, year: 2008

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

    International Nuclear Information System (INIS)

    Mason, J.B.; Selhub, J.

    1988-01-01

    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

  12. Effect of processed and fermented soyabeans on net absorption in enterotoxigenic Escherichia coli-infected piglet small intestine

    NARCIS (Netherlands)

    Kiers, J.L.; Nout, M.J.R.; Rombouts, F.M.; Andel, van E.E.; Nabuurs, M.J.A.; Meulen, van der J.

    2006-01-01

    Infectious diarrhoea is a major problem in both children and piglets. Infection of enterotoxigenic Escherichia coli (ETEC) results in fluid secretion and electrolyte losses in the small intestine. In the present study the effect of processed and fermented soyabean products on net absorption during

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

    DEFF Research Database (Denmark)

    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...

  14. Uptake of Gold Nanoparticles by Intestinal Epithelial Cells: Impact of Particle Size on Their Absorption, Accumulation, and Toxicity.

    Science.gov (United States)

    Yao, Mingfei; He, Lili; McClements, David Julian; Xiao, Hang

    2015-09-16

    Inorganic nanomaterials have been increasingly utilized in many consumer products, which has led to concerns about their potential toxicity. At present, there is limited knowledge about the gastrointestinal fate and cytotoxicity of ingested inorganic nanoparticles. This study determined the influence of particle size and concentration of gold nanoparticles (AuNPs) on their absorption, accumulation, and cytotoxicity in model intestinal epithelial cells. As the mean particle diameter of the AuNPs decreased (from 100 to 50 to 15 nm), their rate of absorption by the intestinal epithelium cells increased, but their cellular accumulation in the epithelial cells decreased. Moreover, accumulation of AuNPs caused cytotoxicity in the intestinal epithelial cells, which was evidenced by depolarization of mitochondria membranes. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity.

  15. High paracellular nutrient absorption in intact bats is associated with high paracellular permeability in perfused intestinal segments.

    Science.gov (United States)

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

    2014-09-15

    Water-soluble nutrients are absorbed by the small intestine via transcellular and paracellular mechanisms. Based on a few previous studies, the capacity for paracellular nutrient absorption seems greater in flying mammals than in nonflying mammals, but there has been little investigation of the mechanisms driving this difference. Therefore, we studied three species each of bats (Artibeus lituratus, Sturnira lilium and Carollia perspicillata) and nonflying mammals (Akodon montensis, Mus musculus and Rattus norvegicus). Using standard pharmacokinetic techniques in intact animals, we confirmed the greater paracellular nutrient absorption in the fliers, comparing one species in each group. Then we conducted in situ intestinal perfusions on individuals of all species. In both approaches, we measured the absorption of 3OMD-glucose, a nonmetabolizable glucose analog absorbed both paracellularly and transcellularly, as well as L-arabinose, which has no mediated transport. Fractional absorption of L-arabinose was three times higher in the bat (S. lilium: 1.2±0.24) than in the rodent (A. montensis: 0.35±0.04), whereas fractional absorption of 3OMD-glucose was complete in both species (1.46±0.4 and 0.97±0.12, respectively). In agreement, bats exhibited two to 12 times higher l-arabinose clearance per square centimeter nominal surface area than rodents in intestinal perfusions. Using L-arabinose, we estimated that the contribution of the paracellular pathway to total glucose absorption was higher in all three bats (109-137%) than in the rodents (13-39%). These findings contribute to an emerging picture that reliance on the paracellular pathway for nutrient absorption is much greater in bats relative to nonflying mammals and that this difference is driven by differences in intestinal permeability to nutrient-sized molecules. © 2014. Published by The Company of Biologists Ltd.

  16. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    Directory of Open Access Journals (Sweden)

    Mazur Andrzej

    2005-10-01

    Full Text Available Abstract Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans.

  17. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    Science.gov (United States)

    Coudray, Charles; Rambeau, Mathieu; Feillet-Coudray, Christine; Tressol, Jean Claude; Demigne, Christian; Gueux, Elyett; Mazur, Andrzej; Rayssiguier, Yves

    2005-01-01

    Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans. PMID:16253138

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

    Science.gov (United States)

    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.

  19. Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study

    DEFF Research Database (Denmark)

    Andersen, Sara Korsgaard; Hardis, Anne L S; Tupper, Oliver Djurhuus

    2018-01-01

    BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby...... compromise absorption of nutrients. AIM: To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven...

  20. 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

    Science.gov (United States)

    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.

  1. Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

    Science.gov (United States)

    Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

    2012-05-01

    In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

  2. Effect of cholecalciferol and 1,25-dihydroxycholecalciferol on the intestinal absorption of zinc in the chick

    International Nuclear Information System (INIS)

    Koo, S.I.; Fullmer, C.S.; Wasserman, R.H.

    1980-01-01

    The effect of cholecalciferol on the intestinal absorption of 65 Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect 65 Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25-dihydroxycholecalciferol increased 47 Ca absorption and induced the synthesis of CaBP but exerted no effect on 65 Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc

  3. Properties of glycerol-75Se-triether: A lipid-soluble marker for the estimation of intestinal fat absorption.

    Science.gov (United States)

    Hoving, J; Valkema, A J; Wilsin, J H; Woldring, M G

    1975-08-01

    The properties of a 75Se-labeled glycerol triether were investigated in rat experiments designed to test this substance as a nonabsorbable marker for the assessment of intestinal fat absorption. After oral administration of 75Se-triether, the radioactivity was excreted almost completely with the feces. Amounts in excess of the quantity required tor clinical use did not interfere with overall fat absorption. No evidence for toxicity of 75Se-triether was observed. 131l-triolein was used as tracer fat and fat absorption was calculated by the following methods: (1) isotope balance method-oral intake minus fecal excretion of 131L; (2) isotope ratio method-comparison of the 131L to 75Se ratios in the test dose and in a stool sample. Results obtained from the isotope ratio method were in close agreement with those of the isotope balance method over a range of fat absorption of 80 to 95 per cent, thus indicating that the marker and the radioactive fat pass the gastrointestinal tract at the same rate under these experimental conditions. These results show that 75Se-triether possesses several of the properties of an ideal marker for fat absorption studies. Its advantages over other proposed markers for fat absorption studies are discussed. Simultaneous administration of 131L-TRIOLEIN AND 75Se-triether in a single dose may provide a reliable, rapid, and simple method to estimate intestinal fat absorption in man.

  4. Does intestinal resection affect the absorption of essential vitamins, minerals, and bile salts? An overview of the literature.

    Science.gov (United States)

    Lambert, Geraldine M

    2008-06-01

    As the number of persons living long lives following ostomy and bowel resection surgery increases, so do their questions about the effect of surgery on chronic conditions commonly associated with aging. The literature was reviewed to evaluate current evidence about the effect of bowel resection on the absorption of vitamins and minerals and related health concerns such as osteoporosis, gallstones, and renal calculi. Present knowledge about the process of vitamin and mineral absorption in the intestine and clinical study results suggest that chronic inflammation and corticosteroid use may adversely affect absorption. In general, a history of bowel resection does not appear to increase the risk of developing osteoporosis, gallstones, or renal calculi and the body can adjust to losing significant sections of intestine. Strategies to help prevent the majority of long-term complications should be encouraged, including monitoring hydration and transit time, consuming low-digestible carbohydrates, and avoiding processed foods as well as agents with chelating properties.

  5. Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat.

    Science.gov (United States)

    He, Xin; Song, Zi-Jing; Jiang, Cui-Ping; Zhang, Chun-Feng

    2017-01-01

    The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

  6. The Prediction of the Relative Importance of CYP3A/P-glycoprotein to the Nonlinear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit Model.

    Science.gov (United States)

    Takano, Junichi; Maeda, Kazuya; Bolger, Michael B; Sugiyama, Yuichi

    2016-11-01

    Intestinal CYP3A and P-glycoprotein (P-gp) decrease the intestinal absorption of substrate drugs. Since substrate specificity of CYP3A often overlaps that of P-gp, and estimation of their saturability in the intestine is difficult, dose-dependent F a F g (fraction of the administered drugs that reach the portal blood) of substrate drugs and the relative importance of CYP3A and P-gp have not been clarified in many cases. Thus, we tried to establish the universal methodology for predicting the in vivo absorption of several CYP3A and/or P-gp substrates from in vitro assays. One of the key points is to set up the scaling factor (SF), correcting the difference between the observed in vivo clearance and the predicted clearance from in vitro data. The SFs of V max for CYP3A (SF CYP3A ) and P-gp (SF P-gp ) were simultaneously optimized to explain the F a F g of CYP3A and/or P-gp substrate drugs. The best predictability of F a F g was achieved when considering both SF CYP3A and SF P-gp The simulation also clarified the relative importance of CYP3A and P-gp in determining F a F g In particular, the nonlinear intestinal absorption of verapamil was caused by the saturation of intestinal CYP3A, whereas that of quinidine was governed by the saturation of both CYP3A and P-gp. In addition, the dose-dependent F a F g of selective and dual CYP3A and/or P-gp substrates was well predicted. We therefore propose a methodology for predicting the F a F g of drugs using a mathematical model with optimized SF CYP3A and SF P-gp Our methodology is applicable to in vitro-in vivo extrapolation of intestinal absorption, even if absolute in vivo functions of enzymes/transporters are unclear. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

    Energy Technology Data Exchange (ETDEWEB)

    Artursson, P.; Karlsson, J. (Uppsala Univ., (Sweden))

    1991-03-29

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10{sup {minus} 8} to 5 x 10{sup {minus} 5} cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10{sup {minus} 6} cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10{sup {minus} 6} cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10{sup {minus} 7} cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption.

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

    Science.gov (United States)

    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).

  9. Techniques and problems in studying intestinal absorption with radioactive isotopes in children

    International Nuclear Information System (INIS)

    James, W.P.T.; Waterlow, J.C.

    1976-01-01

    Radioactive isotopes give substantial promise for assisting the study of gastrointestinal absorption in children in that they allow reduction or elimination of the collection of blood, urine and faeces specimens. These operations are particularly difficult and unreliable in infants, on whom greatest interest in paediatric gastroenterology is centred in the tropics. Here intestinal malabsorption is most commonly associated with malnutrition, lactose intolerance, gastroenteritis, parasitic infestation and iron-deficiency anaemia. Two general techniques that have been employed are whole-body counting and analyses of 14 CO 2 exhaled in the breath after the feeding of 14 C-labelled nutrients. The former is advantageous if radionuclides suitable for the test at hand exist; the latter may be hard to interpret because of problems in the distribution and metabolism of the nutrient and intermediary products. Proper selection and understanding of the tests is particularly important in paediatric work, where the use of radioactive tracer techniques is unacceptable merely for the convenience of the investigator. (author)

  10. Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in intestinal absorption of endothelin receptor antagonist in rats

    DEFF Research Database (Denmark)

    Tani, Takeshe; Gram, Luise Kvisgaard; Arakawa, Hiroshi

    2008-01-01

    PURPOSE: To assess the contribution of organic anion transporting polypeptide 1a5 (Oatp1a5/Oatp3) in the intestinal absorption of an orally active endothelin receptor antagonist, (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylene-dioxyphenyl)cyclopenteno[1,2-b...... and taurocholic acid. CONCLUSIONS: These results consistently suggested that Oatp1a5 is contributing to the intestinal absorption of compound-A at least in part, and the transporter-mediated absorption seems to be maximized at the acidic microenvironment of epithelial cells in the small intestine in rats....

  11. Intrinsic myenteric denervation: a new model to increase the intestinal absorptive surface in short-bowel syndrome.

    Science.gov (United States)

    Garcia, S B; Kawasaky, M C; Silva, J C; Garcia-Rodrigues, A C; Borelli-Bovo, T J; Iglesias, A C; Zucoloto, S

    1999-08-01

    Short-bowel syndrome (SBS) is caused by resection of massive portions of the small intestine and is characterized by symptoms related to malabsorption, of which severe weight loss is the most apparent. Surgical treatments for SBS are not yet satisfactory. In rats, the myenteric denervation by benzalkonium chloride (BAC) leads to development of megaileum with visceral dilatation and mucosal hyperplasia and increases the intestinal transit time. Such operation in the remaining intestinal segment after massive small bowel resection could increase the duration of contact between luminal nutrients and ileal mucosal epithelium, and furthermore, it could increase the superficial area of the mucosa. Thus, our aim in this study was to evaluate the epithelial morphology and body weight changes of animals after intrinsic ileal denervation associated with extensive small intestine resection. Wistar rats were submitted to resection of 80% of small intestinal length (Group R). Another group (B) of animals also received topical serosal application of BAC 0.3%. Control animals were submitted to simulated surgery (Group C). Animals were weighed weekly and sacrificed after 90 days. Intestinal walls were collected for histological procedure and morphometry. At the end of the experimental period all groups showed weight increase, which was reduced in the R group (P < 0.01). Interestingly, the denervated Group B showed a marked increase in weight, similar to the control animals. Morphometric analysis of the mucosal layer area showed a major increase in mucosal surface area, mainly in Group B. Our results showed that the ileal intrinsic denervation associated with massive intestinal resection induced an increase in the superficial absorptive area and was able to improve the postsurgical conditions for the animals, with accentuated weight increase. This procedure may be a useful model for further studies related to the role of the enteric nervous system on intestinal adaptations after

  12. The effects of 18β-glycyrrhetinic acid and glycyrrhizin on intestinal absorption of paeoniflorin using the everted rat gut sac model.

    Science.gov (United States)

    He, Rui; Xu, Yongsong; Peng, Jingjing; Ma, Tingting; Li, Jing; Gong, Muxin

    2017-01-01

    Paeoniflorin (PF), the main active component of Shaoyao-Gancao-tang, possesses significantly antinociceptive effects and many other pharmacological activities. However, its poor intestinal absorption results in low bioavailability. Therefore, enhancing PF absorption plays a vital role in exerting its therapeutic effect. Shaoyao combined with Gancao exhibited a synergistic effect. The enhancement of PF absorption through the interaction of its constituents in intestinal absorption would be greatly implicated. The present study aimed at investigating the effects of glycyrrhizin, the main constituent of Gancao, and its main metabolite, 18β-glycyrrhetinic acid (18β-GA), on the intestinal absorptive behavior of PF, and the role of P-glycoprotein (P-gp) in PF absorption using the in vitro everted rat gut sac model. The results demonstrated that 1 mM of 18β-GA significantly increased PF absorption in both the jejunum and the ileum, while 100 μM of 18β-GA only promoted the ileum absorption and had no obvious effect on the jejunum absorption. The effect of glycyrrhizin on intestinal PF absorption was related to concentrations. One mM of glycyrrhizin significantly increased PF absorption in the jejunum after 45 min and in the ileum after 90 min. But 100 μM of glycyrrhizin had an inhibitory effect in the jejunum and no effect in the ileum before 60 min. Moreover, verapamil, the well-known P-gp inhibitor, could significantly enhance the PF absorption. In conclusion, the influence of 18β-GA and glycyrrhizin on the PF absorption was related to concentrations and intestinal segments. This might be involved in the intervention of efflux transport of PF mediated by intestinal P-gp.

  13. The rate of intestinal glucose absorption is correlated with plasma glucose-dependent insulinotropic polypeptide concentrations in healthy men

    DEFF Research Database (Denmark)

    Wachters-Hagedoorn, Renate E; Priebe, Marion G; Heimweg, Janneke A J

    2006-01-01

    of the factors determining the metabolic quality of different types of carbohydrates. We analyzed the correlation between the rate of intestinal absorption of (starch-derived) glucose and plasma concentrations of GLP-1 and GIP after ingestion of glucose and starchy foods with a different content of rapidly...... and slowly available glucose. In a crossover study, glucose, insulin, GLP-1, and GIP concentrations were monitored for 6 h after consumption of glucose, uncooked cornstarch (UCCS) or corn pasta in 7 healthy men. All test meals were naturally labeled with 13C. Using a primed, continuous D-[6,6-2H2]glucose...... infusion, the rate of appearance of exogenous glucose (RaEx) was estimated, reflecting the rate of intestinal glucose absorption. GLP-1 concentrations increased significantly from 180 to 300 min after ingestion of UCCS, the starch product with a high content of slowly available glucose. A high GIP response...

  14. Synthesis and Physicochemical Evaluation of Entecavir-Fatty Acid Conjugates in Reducing Food Effect on Intestinal Absorption

    Directory of Open Access Journals (Sweden)

    Hyuck Jun Jung

    2018-03-01

    Full Text Available The oral bioavailability of entecavir (EV, an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal absorption of the nucleotide analogue, four lipidic prodrugs were synthesized via the esterification of the primary alcohol of EV with fatty acids (hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid. EV-3-dodecanoate (or EV-C12 exhibited high solubility in a fed state simulated intestinal fluid (78.8 μg/mL, with the acceptable calculated logP value (3.62 and the lowest hydrolysis rate (22.5% for 12 h in simulated gastric fluid, pH 1.2. Therefore, it was chosen as a candidate to improve intestinal absorption of EV, especially under a fed state condition. Physical characterization using scanning electron microscopy, a differential scanning calorimeter, and X-ray powder diffraction revealed that EV-C12 had a rectangular-shaped crystalline form, with a melting point of about 170 °C. In a release test in biorelevant media, such as fasted and fed state-simulated intestinal and/or gastric fluid, more than 90% of the prodrug was released within 2 h in all media tested. These data suggest that this lipidic prodrug might have the potential to alleviate the negative food effect on the intestinal absorption of EV with increased therapeutic efficacy and patient compliance.

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

    Science.gov (United States)

    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. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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

  17. Evidence in favor of a severely impaired net intestinal calcium absorption in patients with (early-stage) chronic kidney disease.

    Science.gov (United States)

    Viaene, L; Meijers, B K I; Vanrenterghem, Y; Evenepoel, P

    2012-01-01

    Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1-4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1-2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD. Copyright © 2012 S. Karger AG, Basel.

  18. [Influence of intake of vegetable oils on the in vitro intestinal absorption of glucose in golden hamsters].

    Science.gov (United States)

    González Barra, I; Escobar, M; Villarroel Guerra, M

    1995-12-01

    Male Hamsters (Mesocricetus aureatus) were fed standardized diets with 15% Rose hip, Sunflower, Olive or Coconut oil for four weeks, in order to determine the influence of vegetable oils with different degree of unsaturation over the intestinal absorption of glucose. The concentration of glucose in the serosal solution at 20, 40 and 60 minutes, was quantified in pieces of everted intestine of each animal, after the feeding period was over. A lower concentration of glucose was observed in the Olive group, although it was statistically significant only when compared to the Rose hip and Coconut oil group (P Rose hip and Coconut showed a similar pattern, even though they are oils with extreme and opposing degree of unsaturation. We explain this by the triggering of homeostatic mechanisms in the cellular membranes of the enterocytes when faced to a nutritional stress caused by the saturated and unsaturated fatty acids of those oils. We can conclude that the in vitro intestinal absorption of glucose in golden hamster is modified by dietary lipids. The lower absorption of glucose seen in the Olive group could be caused a specific action of a fatty acid or of its degree of unsaturation.

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

    Science.gov (United States)

    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

  20. Dietary glutamine supplementation effects on amino acid metabolism, intestinal nutrient absorption capacity and antioxidant response of gilthead sea bream (Sparus aurata) juveniles.

    Science.gov (United States)

    Coutinho, F; Castro, C; Rufino-Palomares, E; Ordóñez-Grande, B; Gallardo, M A; Oliva-Teles, A; Peres, H

    2016-01-01

    A study was undertaken to evaluate dietary glutamine supplementation effects on gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic and intestinal glutamine metabolism and oxidative status. For that purpose gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18% lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2% glutamine for 6weeks. Fish performance, body composition and intestinal nutrient absorption capacity were not affected by dietary glutamine levels. Hepatic and intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were also unaffected by dietary glutamine supplementation. In the intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower than in the liver, suggesting a higher use of glutamine for energy production by the intestine than by the liver. The liver showed higher catalase and glucose-6-phosphate dehydrogenase activities, while the intestine presented higher glutathione peroxidase and glutathione reductase activities and oxidised glutathione content, which seems to reveal a higher glutathione dependency of the intestinal antioxidant response. Total and reduced glutathione contents in liver and intestine and superoxide dismutase activity in the intestine were enhanced by dietary glutamine, though lipid peroxidation values were not affected. Overall, differences between liver and intestine glutamine metabolism and antioxidant response were identified and the potential of dietary glutamine supplementation to gilthead sea bream's antioxidant response was elucidated. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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 (Pabsorption 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The effect of canola meal tannins on the intestinal absorption capacity of broilers using a D-xylose test.

    Science.gov (United States)

    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 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. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  3. Effect of pH, buffer concentration and buffer composition on the absorption of theophylline from the small intestine of the rat

    NARCIS (Netherlands)

    Blaey, C.J. de; Schurgers, N.

    1984-01-01

    The absorption of theophylline from the small intestine of the rat was investigated using buffer solutions of different pH (3.0–9.2), composition and concentration. The technique used, encloses luminal perfusion of an intestinal loop with collection of the blood draining the perfused loop, which

  4. Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein

    International Nuclear Information System (INIS)

    Johnson, W.T.; Canfield, W.K.

    1985-01-01

    65 Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65 Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Zhang

    Full Text Available 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.

  7. Clinical implications of the sugar absorption test: intestinal permeability test to assess mucosal barrier function

    NARCIS (Netherlands)

    Uil, J. J.; van Elburg, R. M.; van Overbeek, F. M.; Mulder, C. J.; vanBerge-Henegouwen, G. P.; Heymans, H. S.

    1997-01-01

    Functional integrity as an aspect of the mucosal barrier function of the small bowel can be estimated by the intestinal permeability for macromolecules. In the first part of this paper, an overview of intestinal permeability and its measurement is given. In the second part of the paper our own

  8. Testing the absorption of the extracts of Coreopsis tinctoria Nutt. in the intestinal canal in rats using an Ussing chamber.

    Science.gov (United States)

    Wang, Jian; Aierken, Guzhalinuer; Li, Xinxia; Li, Linlin; Mao, Xinmin

    2016-06-20

    Coreopsis tinctoria Nutt mainly distributed in Hetian region of Xinjiang at an altitude of 3000m, which is used as Uyghur traditional medicine because of its clearing heat, promoting circulation and removing toxicity and antihypertension, ect. effect. This research was to study the four ingredients in the extracts of Coreopsis tinctoria Nutt. that are absorbed in different intestinal segments in rats to lay the foundation for further study on the effective constituents, tissue distribution, metabolism, and spectrum-effect relationships of these extracts. High, medium, and low concentrations were prepared according to their pharmacological effects. Quantitative analysis multi-components by single marker was used to test the cumulative absorption volume Q, absorption rate constant Ka, and apparent permeability coefficient Papp of the four main ingredients in C. tinctoria Nutt. extract in different intestinal segments in rats using a Ussing chamber model and high-performance liquid chromatography. The Papp of chlorogenic acid and flavanomarein in the duodenum, jejunum, ileum, and colon were 1.0×10(-6) to 10×10(-6)cms(-1). Papp of marein in the duodenum and jejunum was <1.0×10(-6), and was 1.0×10(-6) to 10×10(-6)cms(-1) in the ileum and colon. Papp of 3,5-O-dicaffeoylquinic acid in the duodenum was <1.0×10(-6)cms(-1), while it was 1.0×(1)0(-6) to 10×10(-6)cms(-1) in the jejunum, ileum, and colon. All four chemical components of the plant extract can be absorbed by the intestinal canal of rats, which conforms to zero-order absorption; the ileum presented the best absorption. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. In Situ Intestinal Perfusion in Rodents: Future Perspectives for Application on Absorption Studies and Classification of Drugs.

    Science.gov (United States)

    Dezani, Thaisa Marinho; Dezani, Andre Bersani; de Silva, Monica Maria Coquemala; Dos Reis Serra, Cristina Helena

    2017-01-01

    In 1995, the Biopharmaceutics Classification System (BCS) was proposed by Amidon and colleagues as a tool that considers two important parameters regarding drugs: solubility and permeability. Since then, several methods for solubility and permeability studies have been developed for drug delivery and absorption prediction. In recent years, permeability has gained a great highlight and the interaction between a molecule and a biological membrane is not enough to predict the in vivo behavior of a compound. Thus, different methods for permeability assessment are currently used for mechanistic studies including involvement of carriers and several transport pathways. Furthermore, the investigation regarding metabolism has been a focus in recent researches. Based on this idea, Wu and Benet proposed a new tool called Biopharmaceutics Drug Disposition Classification System (BDDCS), where drugs are classified into four classes considering their solubility and metabolism. Among several methods for permeability studies, the in situ intestinal perfusion is considered the closest to in vivo conditions due advantages as intact blood supply and innervation. This review presents the in situ intestinal perfusion model and its application for permeability/ transport studies of drugs and intestinal metabolism. Also, this paper discusses about how the in situ perfusion studies can be used for classification of drugs and the future perspectives for in vivo absorption prediction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Egg production, faecal pH and microbial population, small intestine morphology, and plasma and yolk cholesterol in laying hens given liquid metabolites produced by Lactobacillus plantarum strains.

    Science.gov (United States)

    Choe, D W; Loh, T C; Foo, H L; Hair-Bejo, M; Awis, Q S

    2012-01-01

    1. Various dosages of metabolite combinations of the Lactobacillus plantarum RI11, RG14 and RG11 strains (COM456) were used to study the egg production, faecal microflora population, faecal pH, small intestine morphology, and plasma and egg yolk cholesterol in laying hens. 2. A total of 500 Lohmann Brown hens were raised from 19 weeks to 31 weeks of age. The birds were randomly divided into 5 groups and fed on various treatment diets: (i) basal diet without supplementation of metabolites (control); (ii) basal diet supplemented with 0·3% COM456 metabolites; (iii) basal diet supplemented with 0·6% COM456 metabolites; (iv) basal diet supplemented with 0·9% COM456 metabolites; and (v) basal diet supplemented with 1·2% COM456 metabolites. 3. The inclusion of 0·6% liquid metabolite combinations, produced from three L. plantarum strains, demonstrated the best effect in improving the hens' egg production, faecal lactic acid bacteria population, and small intestine villus height, and reducing faecal pH and Enterobacteriaceae population, and plasma and yolk cholesterol concentrations. 4. The metabolites from locally isolated L. plantarum are a possible alternative feed additive in poultry production.

  11. Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study.

    Science.gov (United States)

    Andersen, S K; Hardis, A L S; Tupper, O D; Soja, A M B; Nilsson, B; Ulrik, C S; Andersen, J R

    2018-04-01

    Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby compromise absorption of nutrients. To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven with and seven without cor pulmonale. The presence of cor pulmonale was determined by echocardiography. The concentration of d-xylose and zinc were measured in peripheral blood one, two and three hours after ingestion and used as markers of absorption. Furthermore, urine was collected for five hours to determine the amount of excreted d-xylose. No significant difference in absorption of d-xylose (p = 0.28) or zinc (p = 0.51) was found between the two groups. However, a trend towards a delay in d-xylose absorption, as assessed by time-to-peak concentration, was observed in patients with cor pulmonale (p = 0.08). There was no significant difference in the amount of excreted d-xylose in the urine between the groups (p = 0.52). No correlation was found between the tricuspid regurgitation gradient and the absorption of both test-markers (rs = 0.34 and rs = -0.25). Likewise, no correlations were found between the inferior caval pressure during the in- and expiration phases and the absorption of d-xylose (rs = -0.09 rs = 0.23) or zinc (rs = -0.39, rs = -0.39). We found no indications that small intestinal absorption is affected in a clinically relevant degree in patients with cor pulmonale. Copyright © 2018. Published by Elsevier Ltd.

  12. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

    2011-01-01

    Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

  13. Evaluation of the Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity.

    Science.gov (United States)

    Moreira da Silva, Rodrigo; Verjee, Sheela; de Gaitani, Cristiane Masetto; Moraes de Oliveira, Anderson Rodrigo; Pires Bueno, Paula Carolina; Cavalheiro, Alberto José; Peporine Lopes, Norberto; Butterweck, Veronika

    2016-04-22

    The clerodane diterpene casearin X (1), isolated from the leaves of Casearia sylvestris, is a potential new drug candidate due to its potent in vitro cytotoxic activity. In this work, the intestinal absorption mechanism of 1 was evaluated using Caco-2 cells with and without active carboxylesterases (CES). An LC-MS method was developed and validated for the quantification of 1. The estimation of permeability coefficients was possible only under CES-inhibited conditions in which 1 is able to cross the Caco-2 cell monolayer. The mechanism is probably by active transport, with no significant efflux, but with a high retention of the compound inside the cells. The enzymatic hydrolysis assay demonstrates the susceptibility of 1 to first-pass metabolism as substrate for specific CES expressed in human intestine.

  14. Simultaneous determination of eight B-vitamins in rat intestinal perfusate to identify effects of osmotic pressures on absorptions.

    Science.gov (United States)

    Wang, Xiaobo; Xiao, Jian; Zhou, Hui; Qiu, Ying; Peng, Hui; Sun, Yangyang; Zhang, Jiwen; Qian, Wei; Sun, Lixin

    2017-09-01

    A rapid and accurate HPLC-DAD method was developed and validated to simultaneously determine eight B-vitamins (VBs, namely thiamine, riboflavin, niacinamide, calcium pantothenic, pyridoxine, biotin, folic acid and cyanocobalamin) and phenolsulfonphthalein in rat intestinal perfusate. Chromatographic separation was achieved using an Inertsil ODS-3 column (250 × 4.6 mm i.d., 5 μm) at a temperature of 40°C. Gradient elution mode was applied at the flow rate of 1.0 mL/min with the mobile phase of acetonitrile-30 mm K 2 HPO 4 (pH 5.80). The method was successfully applied to identify the effects of osmotic pressures on the absorption of the VBs. The absorption profiles of single and mixed VBs were also compared. Histological section technology was applied to observe the microstructure of small bowel mucosa after perfusion. The results indicated that each compound possessed a better absorption profile under isotonic conditions than under hypotonic or hypertonic conditions for single or mixed solutions. Compared with single VBs, better absorptions in mixed VBs were observed. Pathological tissue slice test suggested that hypotonic and hypertonic solutions changed or damaged the microstructure of mucosa to varying degrees. Taken together, the investigations indicated that multi-VBs administered orally under isotonic condition could generate fast and complete absorption profiles for VBs. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

    2017-12-01

    Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of

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

    Science.gov (United States)

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

    Science.gov (United States)

    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

  18. Effects of the Brown Seaweed Laminaria japonica Supplementation on Serum Concentrations of IgG, Triglycerides, and Cholesterol, and Intestinal Microbiota Composition in Rats

    Directory of Open Access Journals (Sweden)

    Jae-Young Kim

    2018-04-01

    Full Text Available The intestinal microbial communities play critical roles in various aspects of body function of the host. Prebiotics, such as dietary fiber, can affect health of the host by altering the composition of intestinal microbiota. Although brown seaweed Laminaria japonica is rich in dietary fiber, studies on its prebiotic potential are quite rare. In this study, basal diet (control, basal diet supplemented with dried L. japonica (DLJ, heat-treated dried L. japonica (HLJ, or heated dried L. japonica with added fructooligosaccharide (FHLJ was fed to rats for 16 weeks. Serum concentrations of IgG, triglyceride, and cholesterol were measured. In addition, the intestinal microbiota composition was analyzed by high-throughput sequencing of 16S rRNA gene. As compared to the control group, DLJ, HLJ, and FHLJ groups showed significantly higher serum IgG concentration, but had lower weight gain and serum triglyceride concentration. Moreover, DLJ, HLJ, and FHLJ groups showed lower Fimicutes to Bacteroidetes ratio when compared with the control group. As compared with the control group, obesity-associated bacterial genera (Allobaculum, Turicibacter, Coprobacillus, Mollicute, and Oscilibacter, and the genera with pathogenic potentials (Mollicute, Bacteroides, Clostridium, Escherichia, and Prevotella decreased while leanness-associated genera (Alistipes, Bacteroides, and Prevotella, and lactic acid bacterial genera (Subdoligranulum, Streptococcus, Lactobacillus, Enterococcus, and Bifidobacterium increased in all treatment groups. On the contrary, butyric acid producing genera including Subdoligranulum, Roseburia, Eubacterium, Butyrivibrio, and Anaerotruncus increased significantly only in FHLJ group. The overall results support multiple prebiotic effects of seaweed L. japonica on rats as determined by body weight reduction, enhanced immune response, and desirable changes in intestinal microbiota composition, suggesting the great potential of L. japonica as an

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Tsukamoto I

    2014-10-01

    Full Text Available Ikuko Tsukamoto,1,* Akram Hossain,2,3,* Fuminori Yamaguchi,2 Yuko Hirata,2 Youyi Dong,2 Kazuyo Kamitori,2 Li Sui,2 Machiko Nonaka,2 Masaki Ueno,4 Kazuyuki Nishimoto,5 Hirofumi Suda,5 Kenji Morimoto,6 Tsuyoshi Shimonishi,7,† Madoka Saito,8 Tao Song,9 Ryoji Konishi,1 Masaaki Tokuda2 1Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan; 2Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 3Matsutani Chemical Industry Co, Ltd, Itami, Japan; 4Department of Inflammation Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 5Division of Radioisotope Research, Life Science Research Center, Kagawa University, Kagawa, Japan; 6Rare Sugar Research Center, Kagawa University, Kagawa, Japan; 7IZUMORING LLC, Miki, Kita, Kagawa, Japan; 8Department of Pharmacy, Okayama University Hospital, Okayama, Japan; 9The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work†Tsuyoshi Shimonishi has passed away 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

  1. Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

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    Ornella de Bari

    2012-01-01

    Full Text Available The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1, an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD.

  2. Effect of three edible oils on the intestinal absorption of caffeic acid: An in vivo and in vitro study

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    Prasadani, W. Chaturi; Senanayake, Chaturi M.; Jayathilaka, Nimanthi; Ekanayake, Sagarika

    2017-01-01

    Polyphenolic antioxidants are mainly absorbed through passive paracellular permeation regulated by tight junctions. Some fatty acids are known to modulate tight junctions. Fatty acids resulting from the digestion of edible oils may improve the absorption of polyphenolic antioxidants. Therefore, we explored the effect of three edible oils on the intestinal absorption of caffeic acid. Rats were fed with soybean oil and caffeic acid dissolved in distilled water. Caffeic acid contents in the plasma collected up to 1 hr were quantified. The experiment was repeated with coconut oil and olive oil. Component fatty acids of the oils were individually tested in vitro for their effect on permeability of caffeic acid using Caco-2 cell monolayers. Highest absorption of caffeic acid was observed in animals fed with coconut oil. In vitro transport percentages of caffeic acid in 2.5 mmol/L solutions of fatty acids were 22.01±0.12 (lauric), 15.30 ± 0.25 (myristic acid), 13.59 ± 0.35 (linoleic acid), 3.70 ± 0.09 (oleic acid) and 0.10–2.0 (all other fatty acids). Lauric acid and myristic acid are the two major fatty acids present in coconut oil. Therefore, these fatty acids may contribute to the higher absorption of caffeic acid in the presence of coconut oil. PMID:28617858

  3. Physiological and pathological implications of cholesterol.

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    Cortes, Victor A; Busso, Dolores; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2014-01-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

  4. 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.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All

  5. Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.

    Science.gov (United States)

    Wu, Wen; Perrin-Sarrado, Caroline; Ming, Hui; Lartaud, Isabelle; Maincent, Philippe; Hu, Xian-Ming; Sapin-Minet, Anne; Gaucher, Caroline

    2016-10-01

    Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases. Copyright © 2016. Published by Elsevier Inc.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Synthetic LXR Agonist Suppresses Endogenous Cholesterol Biosynthesis and Efficiently Lowers Plasma Cholesterol

    Science.gov (United States)

    Pfeifer, Thomas; Buchebner, Marlene; Chandak, Prakash G.; Patankar, Jay; Kratzer, Adelheid; Obrowsky, Sascha; Rechberger, Gerald N.; Kadam, Rajendra S.; Kompella, Uday B.; Kostner, Gerhard M.; Kratky, Dagmar; Levak-Frank, Sanja

    2011-01-01

    The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid disorders. N,N-dimethyl-3ß-hydroxycholenamide (DMHCA) is a steroidal ligand of LXRs that exerts anti-atherogenic effects in apolipoprotein E-deficient mice without causing negative side effects such as liver steatosis or hypertriglyceridemia. In this report, we investigated the consequences of DMHCA treatment on cholesterol homeostasis in vivo and in vitro. Despite its hydrophobicity, DMHCA is readily absorbed by C57BL/6 mice and taken up by intestinal cells, the lung, heart and kidneys, but is undetectable in the brain. DMHCA significantly reduces cholesterol absorption and uptake in duodenum and jejunum of the small intestine and in turn leads to a reduction of plasma cholesterol by 24%. The most striking finding of this study is that DMHCA inhibited the enzyme 3ß-hydroxysterol-Δ24-reductase resulting in an accumulation of desmosterol in the plasma and in feces. Thus, the reduction of plasma cholesterol was due to a block in the final step of cholesterol biosynthesis. Taken together DMHCA is an interesting compound with properties distinct from other LXR ligands and might be used to study desmosterol-mediated effects in cells and tissues. PMID:21190543

  8. Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model.

    Science.gov (United States)

    Wang, Xiao-Xue; Liu, Gui-Yan; Yang, Yan-Fang; Wu, Xiu-Wen; Xu, Wei; Yang, Xiu-Wei

    2017-09-29

    Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin ( 1 ), glycyrrhetic acid-3- O -mono-β-d-glucuronide ( 2 ), and glycyrrhetinic acid ( 3 ); and the selected major flavonoids, licochalcone A ( 4 ), licochalcone B ( 5 ), licochalcone C ( 6 ), echinatin ( 7 ), isoliquiritin apioside ( 8 ), liquiritigenin ( 9 ), liquiritin apioside ( 10 ) isolated from Glycyrrhizae radix et rhizoma , were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3 , 5 - 7 , and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1 , 8 , and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application.

  9. The use of protein hydrolysate improves the protein intestinal absorption in undernourished mice infected with Schistosoma mansoni

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    Coutinho Eridan M.

    2002-01-01

    Full Text Available Patients residing in endemic areas for schistosomiasis in Brazil are usually undernourished and when they develop the hepatosplenic clinical form of the disease should usually receive hospital care, many of them being in need of nutritional rehabilitation before specific treatment can be undertaken. In the mouse model, investigations carried out in our laboratory detected a reduced aminoacid uptake in undernourished animals which is aggravated by a superimposed infection with Schistosoma mansoni. However, in well-nourished infected mice no dysfunction occurs. In this study, we tried to improve the absorptive intestinal performance of undernourished mice infected with S. mansoni by feeding them with hydrolysed casein instead of whole casein. The values obtained for the coefficient of protein intestinal absorption (cpia among well-nourished mice were above 90% (either hydrolysed or whole protein. In undernourished infected mice, however, the cpia improved significantly after feeding them with hydrolysed casein, animals reaching values close to those obtained in well-nourished infected mice.

  10. Dietary chlorogenic acid improves growth performance of weaned pigs through maintaining antioxidant capacity and intestinal digestion and absorption function.

    Science.gov (United States)

    Chen, Jiali; Li, Yan; Yu, Bing; Chen, Daiwen; Mao, Xiangbing; Zheng, Ping; Luo, Junqiu; He, Jun

    2018-03-16

    Chlorogenic acid (CGA) is a natural phenolic acid, which is an important component of biologically active dietary phenols isolated from various species. Two experiments were conducted to investigate the effects of CGA on growth performance, antioxidant capacity, nutrient digestibility, diarrhea incidence, intestinal digestion and absorption function, and the expression levels of intestinal digestion and absorption-related genes in weaned pigs. In Exp. 1, 200 weaned pigs were randomly allotted to four dietary treatments and fed with a basal diet or a basal diet supplemented with 250, 500, or 1,000 mg/kg CGA, respectively, in a 14-d trial. Pigs on the 1,000 mg/kg CGA-supplemented group had greater (P < 0.05) G:F compared with those on the control (CON) group. In Exp. 2, 24 weaned pigs were randomly allotted to two groups and fed with a basal diet (CON group) or a basal diet supplemented with 1,000 mg/kg CGA (the optimum does from Exp. 1; CGA group). After a 14-d trial, 8 pigs per treatment were randomly selected to collect serum and intestinal samples. Compared with the CON group, the ADG, G:F, as well as the apparent total tract digestibility of CP, crude fat, and ash were increased (P < 0.05), whereas the diarrhea incidence was decreased (P < 0.05) in the CGA group. Pigs on the CGA group had greater (P < 0.05) serum albumin and IGF-1, and lower (P < 0.05) serum urea nitrogen than pigs on the CON group. Furthermore, dietary CGA supplementation enhanced (P < 0.05) the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the serum, the activity of maltase in the jejunum and ileum, as well as the activities of sucrase and alkaline phosphatase (AKP) in the jejunum. The mRNA levels of sodium glucose transport protein-1 (SGLT1) and zinc transporter-1 (ZNT1) in the duodenum and the mRNA levels of SGLT1, glucose transporter-2 (GLUT2), and divalent metal transporter-1 (DMT1) in the jejunum were upregulated (P < 0.05) in pigs fed

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

    Science.gov (United States)

    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.

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

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    Wolfgang Stremmel

    Full Text Available 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.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Intestinal lipid absorption is not affected in CD36 deficient mice

    NARCIS (Netherlands)

    Goudriaan, Jeltje R.; Dahlmans, Vivian E. H.; Febbraio, Maria; Teusink, Bas; Romijn, Johannes A.; Havekes, Louis M.; Voshol, Peter J.

    2002-01-01

    Increasing evidence has implicated the membrane protein CD36 (or fatty acid translocase, FAT) to be involved in high affinity fatty acid uptake. CD36 is expressed in tissues active in fatty acid metabolism, like adipose tissue and skeletal and cardiac muscle, but also in intestine. CD36 is localized

  15. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  16. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    Science.gov (United States)

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. [Phytosterols: another way to reduce LDL cholesterol levels].

    Science.gov (United States)

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  18. Laxative Treatment With Polyethylene Glycol Does Not Affect Lipid Absorption in Rats

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Cuperus, Frans J. C.; Stellaard, Frans; van Dijk, Theo H.; Dekker, Jan; Rings, Edmond H. H. M.; Groen, Albert K.; Verkade, Henkjan J.

    2012-01-01

    Objectives: Polyethylene glycol (PEG) is a frequently used laxative agent. It is unknown, however, whether PEG affects the absorptive capacity of the intestine. Reduced lipid (dietary fat and cholesterol) absorption induced by long-term PEG treatment could negatively affect growth in children. We

  19. Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.

    Science.gov (United States)

    Matsumoto, Yuka; Mochizuki, Wakana; Akiyama, Shintaro; Matsumoto, Taichi; Nozaki, Kengo; Watanabe, Mamoru; Nakamura, Tetsuya

    2017-09-15

    Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans. © 2017. Published by The Company of Biologists Ltd.

  20. Effects of long-term parenteral nutrition on serum lipids, plant sterols, cholesterol metabolism, and liver histology in pediatric intestinal failure.

    Science.gov (United States)

    Kurvinen, Annika; Nissinen, Markku J; Gylling, Helena; Miettinen, Tatu A; Lampela, Hanna; Koivusalo, Antti I; Rintala, Risto J; Pakarinen, Mikko P

    2011-10-01

    Plant sterols (PS) in parenteral nutrition (PN) may contribute to intestinal failure-associated liver disease. We investigated interrelations between serum PS, liver function and histology, cholesterol metabolism, and characteristics of PN. Eleven patients with intestinal failure (mean age 6.3 years) receiving long-term PN were studied prospectively (mean 254 days) and underwent repeated measurements of serum lipids, noncholesterol sterols, including PS, and liver enzymes. PS contents of PN were analyzed. Liver biopsy was obtained in 8 patients. Twenty healthy children (mean age 5.7 years) served as controls. Median percentage of parenteral energy of total daily energy (PN%) was 48%, including 0.9 g · kg(-1) · day(-1) of lipids. Respective amounts of PN sitosterol, campesterol, avenasterol, and stigmasterol were 683, 71, 57, and 45 μg · kg(-1) · day(-1). Median serum concentrations of sitosterol (48 vs 7.5 μmol/L, P liver enzymes remained close to normal range. Glutamyl transferase correlated with serum PS (r = 0.61-0.62, P Liver fibrosis in 5 patients reflected increased serum PS (r = 0.55-0.60, P = 0.16-0.12). Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.

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

    Science.gov (United States)

    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

  2. Transcriptional analysis of porcine intestinal mucosa infected with Salmonella Typhimurium revealed a massive inflammatory response and disruption of bile acid absorption in ileum

    DEFF Research Database (Denmark)

    Uribe, Juber Herrera; Collado-Romero, Melania; Zaldívar-López, Sara

    2016-01-01

    -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...

  3. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  4. Retracted: Advances in the physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Mardones, Pablo; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2013-11-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  5. Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate

    NARCIS (Netherlands)

    Rudolph, G; Kloeters-Plachky, P; Sauer, P; Stiehl, A

    Background Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. Methods We studied

  6. Inhibition of glucose intestinal absorption by kaempferol 3-O-α-rhamnoside purified from Bauhinia megalandra leaves.

    Science.gov (United States)

    Rodríguez, Patricia; González-Mujica, Freddy; Bermúdez, Jairo; Hasegawa, Masahisa

    2010-12-01

    Glucose intestinal absorption (GIA) is one of the factors that increase glycemia. Its reduction could be an important factor in decreasing hyperglycemia in diabetic patients. It has been shown that the aqueous extract of Bauhinia megalandra leaves inhibits GIA. In the present study we identified a compound present in the extract of B. megalandra responsible for the biological effect. The methanol extract of B. megalandra leaves was fractionated using different solvents, and high-speed counter-current chromatography yielding two pure compounds identified by (1)H NMR and (13)C NMR as kaempferol 3-O-α-rhamnoside and quercetin 3-O-α-rhamnoside. The first one increased the K(M) without changes in the V(MAX) of GIA. In addition it exerted an additive inhibitory effect, on GIA, when combined with phlorizin. We suggest that kaempferol 3-O-α-rhamnoside is a competitive inhibitor of intestinal SGLT1 cotransporter. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V; Zimmer, Andreas; Hoefler, Gerald; Hussain, M Mahmood; Groen, Albert K; Kratky, Dagmar

    2016-09-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1(-/-)) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1(-/-) and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp Ctenopharyngodonidella fed graded levels of dietary threonine

    OpenAIRE

    Hong, Yang; Jiang, Weidan; Kuang, Shengyao; Hu, Kai; Tang, Ling; Liu, Yang; Jiang, Jun; Zhang, Yongan; Zhou, Xiaoqiu; Feng, Lin

    2015-01-01

    Background This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp (Ctenopharyngodonidella). Results Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine (P?

  9. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women

    Science.gov (United States)

    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...

  10. Enhanced intestinal absorption activity and hepatoprotective effect of herpetrione via preparation of nanosuspensions using pH-dependent dissolving-precipitating/homogenization process.

    Science.gov (United States)

    Shen, Baode; Jin, Shiying; Lv, Qingyuan; Jin, Shixiao; Yu, Chao; Yue, Pengfei; Han, Jin; Yuan, Hailong

    2013-09-01

    The main purpose of this study was to enhance the intestinal absorption activity and hepatoprotective effect of herpetrione by drug nanosuspensions. Herpetrione nanosuspensions (HNS) were prepared using pH-dependent dissolving-precipitating/homogenization process and then systematically characterized. The intestinal absorption activity of HNS were studied using the recirculating perfusion technique in comparison with herpetrione coarse suspensions (HCS) and pure herpetrione using the recirculating perfusion technique. The protective effect of HNS against acute liver injury induced by carbon tetrachloride (CCl4 ) in mice was also investigated and compared with that of HCS. The mean particle size of HNS was 269 ± 7 nm with a polydispersity index of 0.187 ± 0.021. The result of X-ray powder diffraction indicated that herpetrione was in amorphous state in both coarse powder and nanosuspensions. The intestinal absorption activity of HNS were superior to the HCS and pure herpetrione. As evidenced by the lowering of serum aminotransferase levels and the improvement of the degree of liver lesion, pretreatment with HNS markedly enhanced the hepatoprotective effect of herpetrione against acute liver injury induced by CCl4 in mice. HNS prepared using pH-dependent dissolving-precipitating/homogenization technique are able to significantly enhance the intestinal absorption activity and the hepatoprotective effect of herpetrione due to the particle size reduction. © 2013 Royal Pharmaceutical Society.

  11. Intestinal absorption of the antiepileptic drug substance vigabatrin in Göttingen mini-pigs is unaffected by co-administration of amino acids

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Holm, René; Thale, Zia Irene

    2014-01-01

    The anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro evidence suggests that vigabatrin is transported via the proton coupled amino acid transporter (PAT1). The aim of the present study was to investigate whether the intestinal absorption of vigabatrin in vivo...

  12. Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin.

    Science.gov (United States)

    Bergamaschi, Gaetano; Di Sabatino, Antonio; Pasini, Alessandra; Ubezio, Cristina; Costanzo, Filippo; Grataroli, Davide; Masotti, Michela; Alvisi, Costanza; Corazza, Gino R

    2017-10-01

    Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin. The transcriptional response of human duodenal mucosa to hepcidin was investigated using organ cultures of duodenal biopsies perendoscopically collected from healthy controls. Biopsies were cultured for 4 h with or without hepcidin-25 and were then assayed for the expression of iron-related genes. In samples that had not been exposed to hepcidin, correlations were found between the expression of genes involved in iron absorption: DMT1, Fpn1, Dcytb and HCP1. In ex vivo experiments hepcidin down-regulated mRNA levels of the iron transporters Fpn1, and DMT1, of the ferric reductase Dcytb, of the ferroxidase hephaestin, and of the putative heme carrier protein HCP1. Through the reported transcriptional changes hepcidin can modulate several steps of the iron absorption process, including the reduction of dietary iron by Dcytb, its uptake by enterocytes through DMT1, the mucosal uptake of heme iron by HCP1, and enterocyte iron release to plasma by Fpn1 in conjunction with hephaestin. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine

    OpenAIRE

    Selby-Pham, Sophie N. B.; Miller, Rosalind B.; Howell, Kate; Dunshea, Frank; Bennett, Louise E.

    2017-01-01

    A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predi...

  14. Effect of gastric anacidity on the intestinal absorption of liver bound 57Co-labelled cobalamins

    International Nuclear Information System (INIS)

    Kittang, E.

    1987-01-01

    57 Co-labelled cyanocobalamin injected in rabbit was transformed within the liver to 57 Co-labelled desoxyadenosylcobalamin and methylcovalamin. The absorption of 57 Co-labelled liver bound cobalamins could be determined with acceptable accuracy by the double isotope fecal excretion method. Treatment with the H 2-receptor antagonist, ranitidine, did not result in decreased absorption of 57 Co-labelled liver bound cobalamins in healthy individuals. R-protein and the R-proteincobalamin complex were determined by the FPLC Mono S chromatography method with a high degree of correlation to the charcoal method in saliva, gastric and duodenal juice, and with a high degree of reproducibility. Omeprazole markedly inhibited the gastric acid and pepsin secretion, but did nor inhibit the IF secretion. Omeprazole treatment resulted in anacidity in 14 of 17 individuals, but did not reduce the absorption of liver bound 57 Co-labelled cobalamins. The intrinsic factor concentration in gastric aspirates measured during the study was unchanged during omeprazole treatment. The release of cobalamins from liver homogenate was markedly inhibited by neutralized gastric juice in vitro, probably due to decreased pepsin mediated proteolysis. In vivo the cobalamin release from liver homogenate was modestly inhibited in the stomach but was unaffected in jejunum during omeprazole treatment. The major part of 57 Co-labelled liver cobalamins bound to R-protein in acid and neutral gastric juice in vitro, and omeprazole induced anacidity, did not influence the cobalamin binding either in gastric or jejunal juice in vivo

  15. Intestinal phosphate absorption is mediated by multiple transport systems in rats.

    Science.gov (United States)

    Candeal, Eduardo; Caldas, Yupanqui A; Guillén, Natalia; Levi, Moshe; Sorribas, Víctor

    2017-04-01

    Apical inorganic phosphate (P i ) transport in the small intestine seems to be mainly mediated by the sodium/P i cotransporter NaPi2b. To verify this role, we have studied the combined effects of pH, phosphonoformate, and P i deprivation on intestinal P i transport. Rats were fed, ad libitum, three fodders containing 1.2, 0.6, or 0.1% P i for 1, 5, or 10 days. P i deprivation (0.1%) increased both sodium-activated and sodium-independent P i transport in brush-border membrane vesicles from the duodenum and jejunum for all three times. Alkaline pH inhibited P i transport, despite the increasing concentration of [Formula: see text] (NaPi2b substrate), whereas acidity increased transport when the concentration of the PiT1/PiT2 substrate, [Formula: see text], was at its highest. The effect of P i deprivation was maximal at acid pH, but both basal and upregulated transport were inhibited (70%) with phosphonoformate, an inhibitor of NaPi2b. PiT2 and NaPi2b protein abundance increased after 24 h of P i deprivation in the duodenum, jejunum, and ileum, whereas PiT1 required 5-10 days in the duodenum and jejunum. Therefore, whereas transporter expressions are partially correlated with P i transport adaptation, the pH effect precludes NaPi2b, and phosphonoformic acid precludes PiT1 and PiT2 as the main transporters. Transport and transporter expression were also inconsistent when feeding was limited to 4 h daily, because the 1.2% P i diet paradoxically increased P i transport in the duodenum and jejunum, but NaPi2b and PiT1 expressions only increased with the 0.1% diet. These findings suggest the presence of a major transporter that carries [Formula: see text] and is inhibited by phosphonoformate. NEW & NOTEWORTHY The combined effects of dietary inorganic phosphate (P i ) content, pH, and phosphonoformate inhibition suggest that the resulting apical P i transport in the small intestine cannot be fully explained by the presence of NaPi2b, PiT1, or PiT2. We provide evidence of

  16. Enhanced intestinal absorption of curcumin in Caco-2 cell monolayer using mucoadhesive nanostructured lipid carriers.

    Science.gov (United States)

    Chanburee, Sanipon; Tiyaboonchai, Waree

    2018-02-01

    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  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, 106B: 734-741, 2018. © 2017 Wiley Periodicals, Inc.

  17. Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA).

    Science.gov (United States)

    Petit, Charlotte; Bujard, Alban; Skalicka-Woźniak, Krystyna; Cretton, Sylvian; Houriet, Joëlle; Christen, Philippe; Carrupt, Pierre-Alain; Wolfender, Jean-Luc

    2016-03-01

    At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high

  18. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    Science.gov (United States)

    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.

  19. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

    Science.gov (United States)

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-01-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

  20. Relevance of hereditary defects in lipid transport proteins for the pathogenesis of cholesterol gallstone disease

    NARCIS (Netherlands)

    vanBerge-Henegouwen, G. P.; Venneman, N. G.; Portincasa, P.; Kosters, A.; van Erpecum, K. J.; Groen, A. K.

    2004-01-01

    In the formation of cholesterol gallstones, cholesterol hypersecretion into bile causing cholesterol supersaturation and crystallization appears to be the primary factor, with disturbed gallbladder and intestinal motility as secondary factors. Although intestinal uptake mechanisms have not yet been

  1. Intestinal absorption of coenzyme Q(10) administered in a meal or as capsules to healthy subjects

    DEFF Research Database (Denmark)

    Weber, Christine; Bysted, Anette; Hølmer, Gunhild Kofoed

    1997-01-01

    A randomized cross-over study by supplementation with single doses of coenzyme Q(10) (30 mg/person), administered either as a meal consisting of cooked pork heart or as 30 mg coenzyme Q(10) capsules was performed to investigate the bioavailability of dietary coenzyme Q(10) in humans. The increase...... in serum coenzyme Q(10) concentration was used as an index of the absorption, and reached a maximum six hours after the ingestion of either meal or capsules. Following intake of coenzyme Q(10) capsules, the serum coenzyme Q(10) concentrations increased significantly (p...

  2. Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine

    DEFF Research Database (Denmark)

    Madsen, Jan L.; Sjögreen-Gleisner, Katarina; Elema, Dennis Ringkjøbing

    2014-01-01

    , every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [75Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87•9 (SD 3•3)% of the administered activity of [75Se...... imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet....

  3. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine

    International Nuclear Information System (INIS)

    Duval, Caroline; Touche, Veronique; Tailleux, Anne; Fruchart, Jean-Charles; Fievet, Catherine; Clavey, Veronique; Staels, Bart; Lestavel, Sophie

    2006-01-01

    Niemann-Pick C1 like 1 (NPC1L1) is a protein critical for intestinal cholesterol absorption. The nuclear receptors peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRα and LXRβ) are major regulators of cholesterol homeostasis and their activation results in a reduced absorption of intestinal cholesterol. The goal of this study was to define the role of PPARα and LXR nuclear receptors in the regulation of NPC1L1 gene expression. We show that LXR activators down-regulate NPC1L1 mRNA levels in the human enterocyte cell line Caco-2/TC7, whereas PPARα ligands have no effect. Furthermore, NPC1L1 mRNA levels are decreased in vivo, in duodenum of mice treated with the LXR agonist T0901317. In conclusion, the present study identifies NPC1L1 as a novel LXR target gene further supporting a crucial role of LXR in intestinal cholesterol homeostasis

  4. Increased intestinal absorption by segmental reversal of the small bowel in adult patients with short-bowel syndrome: a case-control study.

    Science.gov (United States)

    Layec, Sabrina; Beyer, Laura; Corcos, Olivier; Alves, Arnaud; Dray, Xavier; Amiot, Aurélien; Stefanescu, Carmen; Coffin, Benoit; Bretagnol, Frédéric; Bouhnik, Yoram; Messing, Bernard; Panis, Yves; Kapel, Nathalie; Joly, Francisca

    2013-01-01

    Segmental reversal of the small bowel (SRSB) is proposed in patients with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on absorption have not been studied. We aimed to determine intestinal macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS patients with intestinal failure. We included in a retrospective study all consecutive patients who had an SRSB between 1985 and 2010 and underwent a study of macronutrient absorption. Patients were matched to SBS controls with the same digestive characteristics. Energy and macronutrient absorption were measured. The dependence on HPN was expressed by the number of infusions per week and by the calories infused daily divided by the basal energy expenditure multiplied by 1.5. Seventeen patients who had an SRSB were matched to 17 control patients. Intestinal absorption was higher in the SRSB group for total calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% ± 38.4% in the SRSB group, whereas it was 79% ± 39.6% in the control group (P < 0.05). The number of calories infused was lower in the SRSB group (500 ± 283 compared with 684 ± 541; P < 0.05), as was HPN dependence (33% ± 20% compared with 48% ± 38%; P < 0.05) at the time of the study. SRSB allows a gain in macronutrient absorption, which is associated with a lower HPN dependence. To our view, SRSB should be integrated in intestinal rehabilitative adult programs.

  5. On the relationship between glucose absorption and glucose‐stimulated secretion of GLP‐1, neurotensin, and PYY from different intestinal segments in the rat

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Christiansen, Charlotte Bayer; Saltiel, Monika Yosifova

    2017-01-01

    characterized, and it remains uncertain how their secretion is related to glucose absorption. We isolated and perfused either the upper (USI) or the lower (LSI) small intestine or the colon from rats and investigated concomitant glucose absorption and secretory profiles of GLP‐1, NT, and PYY. In the USI and LSI...... the LSI and from the USI and colon, but the responses in the USI and colon were 5‐ to 15‐fold lower than in the LSI. Glucose was absorbed to a comparable extent in the USI and LSI by mechanisms that partly depended on both SGLT1 and GLUT2 activity, whereas the absorption in the colon was 80–90% lower....... The absorption rates were, however, similar when adjusted for segmental length. Glucose absorption rates and NT, PYY and in particular GLP‐1 secretion were strongly correlated (P

  6. Transfer of milk prolactin ro the plasma of neonatal rats by intestinal absorption

    International Nuclear Information System (INIS)

    Whitworth, N.S.; Grosvenor, C.E.

    1978-01-01

    Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. 131 - labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with 131 I-labelled rat prolactin and after the pups had received 131 I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the 131 I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10.5 or 21.0 μg B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46.2 μg B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13-to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn is permeable to prolactin and that milk may constitute an exogeneous source of prolactin for the suckled offspring. (author)

  7. The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial.

    Science.gov (United States)

    Lin, X; Racette, S B; Lefevre, M; Spearie, C A; Most, M; Ma, L; Ostlund, R E

    2010-12-01

    Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers. The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), Pphytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), Pphytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

  8. Vitamin B 12 absorption: correction of intestinal retention by whole-body profile activity of vitamin B 12-58 cobalt and by double tracer technique

    International Nuclear Information System (INIS)

    Goncalves, M.R. Bencke; Gheldof, R.; Paternot, L. van Tricht; Delmotte, E.; Verschaeren, A.; Martin, P.; Verhas, M.; Universidade Federal, Rio de Janeiro, RJ

    1997-01-01

    Full text. Intestinal retention could give false negative results in determining the whole-body retention of vitamin B 12 absorption (WBC B12-58Co). After having validate the WBC B12-58Co, taking the Schilling test as reference, we have studied the feasibility to evaluate the intestinal contamination by measurement of the profile activity distribution of vitamin B12-58Co and by a double tracer technique (WBC B12-58Co/ WBC 51 Cr Cl3). Methodology: twenty five patients were studied for the setting up of the new methodology. For eleven of them the WBC B12-58 Co retention was measured at the 7th day after the oral administration of 37KBq of B12-58Co using a four detectors whole body counter. One week later, a Schilling test was performed after the oral absorption of 18,5 KBq B12-57Co. Results were expressed as %ID. In these patients, one single peak of hepatic activity was observed on the whole body profile and thus no further intestinal correction was needed. In order to evaluate the intestinal contribution, we made in nine other patients the profile of the whole body distribution of activity at 1 h, 1 week and two weeks after the oral administration of B12-58Co. For five other patients a double tracer technique was used for intestinal correction after the simultaneous oral administration of 37 KBq of B12-58Co and 1,85 MBq of 51 Cr Cl3. The B12-58Co absorption was evaluated after intestinal correction based on subtraction of the 51Cr Cl3 contribution after the formula: B12-58Co(%ID) = WBC B12-58Co - WBC 51 Cr Cl3/1 - WBC 51 Cr Cl3. Results: the correlation with the Schilling test was found excellent: r=0,94 (n=11). The normality for WBC retention (n=7) was define as 53,2 +-12,4% ID (SD). For nine patients studied at the 7th day, the presence of a double peak (hepatic and intestinal peaks) allowed the subtraction by exponential extrapolation; the correction range was 4,4% to 37,2%. With the exception of one observation there was no difference in the measure of vitamin

  9. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Effects of steroids and sex reversal on intestinal absorption of L-[14C]leucine in vivo, in rainbow trout, Salmo gairdneri

    International Nuclear Information System (INIS)

    Habibi, H.R.; Ince, B.W.

    1983-01-01

    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-[ 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 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 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

  11. L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats

    Directory of Open Access Journals (Sweden)

    Qiongxian Yan

    2017-01-01

    Full Text Available L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration.

  12. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  13. Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine.

    Science.gov (United States)

    Selby-Pham, Sophie N B; Miller, Rosalind B; Howell, Kate; Dunshea, Frank; Bennett, Louise E

    2017-05-16

    A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (T max ) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts T max of dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict T max of dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.

  14. Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach.

    Science.gov (United States)

    Sun, Jing; Dahan, Arik; Amidon, Gordon L

    2010-01-28

    A prodrug strategy was applied to guanidino-containing analogues 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 (IC(50): 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 (k(cat)/K(m) in mM(-1) x 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 analogues via targeting hPEPT1 for transport and hVACVase for activation.

  15. Regulation of Bile Acid and Cholesterol Metabolism by PPARs

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2009-01-01

    Full Text Available Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARα alters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.

  16. 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

    DEFF Research Database (Denmark)

    Jeppesen, P B; Lund, P; Gottschalck, I B

    2009-01-01

    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......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...... 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...

  17. Red grape skin and seeds polyphenols: Evidence of their protective effects on endothelial progenitor cells and improvement of their intestinal absorption.

    Science.gov (United States)

    Felice, Francesca; Zambito, Ylenia; Di Colo, Giacomo; D'Onofrio, Claudio; Fausto, Catia; Balbarini, Alberto; Di Stefano, Rossella

    2012-01-01

    To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) from oxidative stress induced by hyperglycemia (HG) compared to red wine (RW) and prepare innovative pharmaceutical systems for the oral administration of red grape extract allowing the overcoming of its poor intestinal absorption. Human EPC were characterized by expression of cell surface markers. Cells were incubated with different concentrations of total polyphenols from grape components or RW in the presence or absence of HG. Cell viability, migration, adhesion, and reactive oxygen species (ROS) production were assayed. Intestinal permeation of polyphenols was studied in the absence or presence of a quaternary ammonium-chitosan conjugate (N⁺(60)-Ch). Grape components and RW increased EPC viability, adhesion and migration, and prevented the HG effect (P grape seed extract and RW (P polyphenol permeability across the excised rat intestine. Red grape components are a source of antioxidant compounds that ameliorate EPC viability and function, while preventing endothelial dysfunction. The use of polycationic chitosan derivatives can promote the absorption of polyphenols across intestinal epithelium, thus increasing their bioavailability and potential therapeutic value in atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Investigation of the effects of soluble fibers on the absorption of resveratrol and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) in the Caco-2 cellular model of intestinal absorption.

    Science.gov (United States)

    Willenberg, Ina; Wonik, Jasmin; Schebb, Nils Helge

    2015-01-01

    Soluble fibers are known to modulate intestinal absorption of non-polar compounds in the small intestine. Little is known about the modulation of absorption of more polar compounds. In the present study, we applied the Caco-2-transwell-system in order to investigate the modulation of intestinal bioavailability by soluble fibers. The system was tested using pectin and carrageenan as model soluble fibers at a concentration of 0.1% (w/v), which did not compromise the integrity of the cell monolayer. Modulation of absorption was evaluated for the heterocyclic amine aromatic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) and the polyphenol resveratrol. Neither pectin nor carrageenan reduced the high flux of PHIP, apparent permeability coefficient (Papp) of 16 × 10(-6) cm s(-1). The low Papp of resveratrol was reduced by both soluble fibers, particularly by pectin. These results suggest that the low bioavailability of polyphenols could be further reduced by soluble fibers. Because of their co-occurrence in several fruits, these findings warrant further research.

  19. Tissue sterol composition in Atlantic salmon (Salmo salar L.) depends on the dietary cholesterol content and on the dietary phytosterol:cholesterol ratio, but not on the dietary phytosterol content.

    Science.gov (United States)

    Sissener, Nini H; Rosenlund, Grethe; Stubhaug, Ingunn; Liland, Nina S

    2018-03-01

    The aim of the study was to investigate how the dietary sterol composition, including cholesterol, phytosterol:cholesterol ratio and phytosterols, affect the absorption, biliary excretion, retention, tissue storage and distribution of cholesterol and individual phytosterols in Atlantic salmon (Salmo salar L.). A feeding trial was conducted at two different temperatures (6 and 12°C), using nine different diets with varying contents of phytosterols, cholesterol and phytosterol:cholesterol ratio. Cholesterol retention values were clearly dependent on dietary cholesterol, and showed that fish fed cholesterol levels phytosterol:cholesterol ratio, but not on the dietary phytosterol content in itself. Campesterol and brassicasterol appeared to be the phytosterols with the highest intestinal absorption in Atlantic salmon. There was a high biliary excretion of campesterol, but not of brassicasterol, which accumulated in tissues and particularly in adipose tissue, with 2-fold-higher retention at 12°C compared with 6°C. Campesterol had the second highest retention of the phytosterols in the fish, but with no difference between the two temperatures. Other phytosterols had very low retention. Although brassicasterol retention decreased with increasing dietary phytosterols, campesterol retention decreased with increasing dietary cholesterol, indicating differences in the uptake mechanisms for these two sterols.

  20. Acupuncture Improves Intestinal Absorption of Iron in Iron-deficient Obese Patients: A Randomized Controlled Preliminary Trial.

    Science.gov (United States)

    Xie, Xin-Cai; Cao, Yan-Qiang; Gao, Qian; Wang, Chen; Li, Man; Wei, Shou-Gang

    2017-03-05

    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). 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. 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 vs. 8.13 ± 0.55 ng/ml, P vs. 6.77 ± 0.84 ng/ml, P acupuncture group than those in the control group. 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 systemic leptin-hepcidin levels.

  1. Mechanisms of mercurial and arsenical inhibition of tyrosine absorption in intestine of the winter flounder Pseudopleuronectus americanus

    International Nuclear Information System (INIS)

    Musch, M.W.; Chauncey, B.; Schmid, E.C.; Kinne, R.K.; Goldstein, L.

    1990-01-01

    Effects of HgCl2 (100 microM) para-chloromercuribenzene sulfonate (PCMBS) (1 mM), and oxophenylarsine (OPA) (250 microM) were determined on (a) the rate of Na pump activity in intact winter flounder intestine; (b) activity of Na-K-ATPase in tissue homogenates; and (c) Na-dependent and Na-independent uptake of tyrosine in brush border membrane vesicles. Initial rate of uptake (influx) of 86Rb from the serosal solution of tissues mounted in Ussing chambers, a measure of Na-K-ATPase activity in the intact cell, was inhibited by all three agents with differing time courses. Rapidly permeating HgCl2 inhibited influx to the same degree as ouabain at 30 min, whereas the effects of PCMBS and OPA required 90 min. Cell potassium was also measured as an indirect indicator of ATPase activity and cell membrane permeability. All three agents decreased cell K, although effects on cell K lagged behind those for inhibition of the ATPase. At the concentrations used in the Ussing chamber (or at one-tenth concentration), all agents completely inhibited Na-K-ATPase activity in enzyme assays performed with tissue homogenates. In contrast, only HgCl2 decreased Na-dependent uptake of tyrosine by brush border membrane vesicles. These results suggest that mercurial and arsenical effects on tyrosine absorption are due to inhibition of the Na-K-ATPase thus decreasing the driving force for the cellular uptake by the Na-tyrosine cotransport system. Direct effects on Na-tyrosine cotransport may play a role in the inhibition observed with HgCl2, but not for PCMBS or OPA

  2. [THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Malyshev, P P; Amelyushkina, V A; Aripovsky, A V; Smirnov, G P; Polevaya, T Yu; Kabo, S I; Kukhartchuk, V V

    2015-10-01

    The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and

  3. Improvement of intestinal absorption of forsythoside A and chlorogenic acid by different carboxymethyl chitosan and chito-oligosaccharide, application to Flos Lonicerae-Fructus Forsythiae herb couple preparations.

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    Full Text Available The current study aims to investigate the effect of chitosan derivatives on the intestinal absorption and bioavailabilities of forsythoside A (FTA and Chlorogenic acid (CHA, the major active components in Flos Lonicerae-Fructus Forsythiae herb couple. Biopharmaceutics and pharmacokinetics properties of the two compounds have been characterized in vitro, in situ as well as in rats. Based on the identified biopharmaceutics characteristics of the two compounds, the effect of chitosan derivatives as an absorption enhancer on the intestinal absorption and pharmacokinetics of FTA and CHA in pure compound form as well as extract form were investigated in vitro, in situ and in vivo. Both FTA and CHA demonstrated very limited intestinal permeabilities, leading to oral bioavailabilities being only 0.50% and 0.13% in rats, respectively. Results from both in vitro, in situ as well as in vivo studies consistently indicated that Chito-oligosaccharide (COS at dosage of 25 mg/kg could enhance intestinal permeabilities significantly as well as the in vivo bioavailabilities of both FTA and CHA than CMCs in Flos Lonicerae-Fructus Forsythiae herb couple preparations, and was safe for gastrointestine from morphological observation. Besides, treatment with Flos Lonicerae-Fructus Forsythiae herb couple preparations with COS at the dosage of 25 mg/kg prevented MDCK damage after influenza virus propagation, which was significantly better than control. The current findings not only identified the usefulness of COS for the improved delivery of Flos Lonicerae-Fructus Forsythiae preparations but also demonstrated the importance of biopharmaceutical characterization in the dosage form development of traditional Chinese medicine.

  4. 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.

    Science.gov (United States)

    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 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. Copyright © 2012 American Society for Bone and Mineral Research.

  5. Investigating drug absorption from the colon: Single-pass vs. Doluisio approaches to in-situ rat large-intestinal perfusion.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; Zur, Moran; Fine-Shamir, Noa; Markovic, Milica; Cohen, Yael; Porat, Daniel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival; Dahan, Arik

    2017-07-15

    Traditionally, the colon is considered a secondary intestinal segment in the drug absorption process. However, in many cases the role of colonic drug permeability cannot be overlooked. The purpose of this research was to compare colon permeability data obtained using two different rat perfusion methods the single-pass intestinal perfusion (SPIP) approach and the closed-loop (Doluisio) perfusion model. A list of 14 structurally diverse model drugs was constructed, and their rat colon permeability was studied using the two methods. The two sets of results were compared to each other, and were evaluated vs. in-vitro, ex-vivo, and in-vivo literature values. The SPIP and the Doluisio results exhibited good correlation between them (R 2 =0.81). The best correlation of both sets was obtained with transport studies across Caco-2 monolayers (R 2 ∼0.9), as well as the sigmoidal fit vs. human fraction of dose absorbed (F abs ) data. On the other hand, Ussing chambers data, as well as lipophilicity (Log P) data, resulted in weak correlation to the in-situ results. In conclusion, the single-pass intestinal perfusion (SPIP) and the Doluisio (closed-loop) perfusion models were found to be equally convenient and useful for obtaining validated colon permeability values, although more human colonic F abs data are needed for a better understanding of colonic drug permeability and absorption. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress.

    Science.gov (United States)

    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 (H 2 O 2 ) 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. The Importance of Wireless Capsule Endoscopy for Research into the Intestin al Absorption Window of 5-Aminosalicylic Acid in Experimental Pigs.

    Science.gov (United States)

    Kvetina, Jaroslav; Tacheci, Ilja; Nobilis, Milan; Kopacova, Marcela; Kunes, Martin; Bures, Jan

    2017-01-01

    Absorption windows in particular segments of the small intestine can contribute to the development of orally administered drug formulations and can limit the bioavailability of released compounds. The aim of this study was to evaluate use of wireless capsule enteroscopy regarding the disintegration kinetic process of tablets in the small intestine and its comparison with the levels of the model drug (5- aminosalicylic acid; 5-ASA), and its majority metabolite (N-acetyl-5-aminosalicylic acid; N-acetyl-5-ASA) in blood plasma. Tablets were endoscopically introduced into the duodenum and their disintegration was monitored using wireless capsule enteroscopy in anaesthetised pigs. In parallel, blood plasma time profiles of the model drug (5-ASA) released from tablets and its metabolite (N-acetyl-5-ASA) were detected. The disintegration of tablets was evident in the proximal jejunum (until the 90-minute mark) and culminated at the 3rd hour. The maximum plasmatic concentration of 5-ASA was reached at the 3rd hour and in the case of its metabolite (N-acetyl-5-ASA) at the 4th hour. The study demonstrated the advantage of combination of wireless capsule enteroscopy and bioanalytical determination of pharmacokinetic parameters in an animal experiment to localise the disintegration site of solid dosage form and following kinetics of intestinal absorption of the released active agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

    Directory of Open Access Journals (Sweden)

    Todd C Rideout

    2008-10-01

    Full Text Available Todd C Rideout1, Scott V Harding1, Peter JH Jones1, Ming Z Fan21Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; 2Centre for Nutrition Modeling, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, CanadaAbstract: The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in ‘high-dimensional’ biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of ‘omic’ technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based “cocktails” that target specific metabolic pathways to gain maximal cholesterol reductions.Keywords: dietary fiber, cholesterol, bile acids, gene, protein

  9. A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products

    NARCIS (Netherlands)

    Minekus, M.; Smeets-Peeters, M.; Havenaar, R.; Bernalier, A.; Fonty, G.; Marol-Bonnin, S.; Alric, M.; Marteau, P.; Huis Veld, J.H.J. in 't

    1999-01-01

    This paper introduces a new type of system to simulate conditions in the large intestine. This system combines removal of metabolites and water with peristaltic mixing to obtain and handle physiological concentrations of microorganisms, dry matter and microbial metabolites. The system has been

  10. Studies on the mechanism of cholesterol uptake and on the effects of bile salts on this uptake by brush-border membranes isolated from rabbit small intestine.

    Science.gov (United States)

    Proulx, P; Aubry, H; Brglez, I; Williamson, D G

    1984-12-19

    The effect of bile salts and other surfactants on the rate of incorporation of cholesterol into isolated brush-border membranes was tested. At constant cholesterol concentration, a stimulatory effect of taurocholate was noticed which increased as the bile salt concentration was raised to 20 mM. Taurodeoxycholate was as effective as taurocholate at concentrations of up to 5 mM and inhibited at higher concentrations. Glycocholate was only moderately stimulatory whereas cholate was nearly as effective as taurocholate at concentrations above 5 mM. Other surfactants such as sodium lauryl sulfate and Triton X-100 were very inhibitory at all concentrations tried whereas cetyltrimethyl ammonium chloride was stimulatory only at a very low range of concentrations. These micellizing agents all caused some disruption of the membranes and the greater effectiveness of taurocholate in stimulating sterol uptake was partly relatable to the weaker membrane solubilizing action of this bile salt. Preincubation of membranes with 20 mM taurocholate followed by washing and exposure to cholesterol-containing lipid suspensions lacking bile salt, did not enhance the incorporation of the sterol. In the absence of bile salt the incorporation of cholesterol was unaffected by stirring of the incubation mixtures. Increasing the cholesterol concentration in the mixed micelle while keeping the concentration of bile salt constant caused an increase in rate of sterol incorporation. This increased rate was seen whether the cholesterol suspension was turbid, i.e., contained non-micellized cholesterol, or whether it was optically-clear and contained only monomers and micelles. When the concentration of taurocholate and cholesterol were increased simultaneously such that the concentration ratio of these two components was kept constant, there resulted a corresponding increase in rate of cholesterol uptake. The initial rates of cholesterol incorporation from suspensions containing micellar and monomer

  11. Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome.

    Science.gov (United States)

    Chan, Dick C; Watts, Gerald F; Barrett, P Hugh R; O'Neill, Frans H; Thompson, Gilbert R

    2003-04-01

    The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.

  12. Decreased intestinal calcium absorption in vivo and normal brush border membrane vesicle calcium uptake in cortisol-treated chickens: evidence for dissociation of calcium absorption from brush border vesicle uptake.

    Science.gov (United States)

    Shultz, T D; Bollman, S; Kumar, R

    1982-06-01

    The influence of cortisol on intestinal calcium transport was studied in isolated duodenal loops and brush border membrane (BBM) vesicles of vitamin D-deficient or replete chickens. Four- to five-week-old vitamin D-deficient cockerels were dosed intraperitoneally with 1 microgram of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] alone 15 hr before sacrifice or in combination with 1, 3, or 5 mg of cortisol 24 and 48 hr before sacrifice. After a 1-microgram dose of 1,25-)OH)2D3 the in situ intestinal ligated loop technique revealed a 60% increase in calcium absorption compared to control birds (P less than or equal to 0.001). However, the administration of cortisol in various doses (3 and 5 mg) to chickens given 1,25-(OH)2D3 resulted in significant decreases in intestinal calcium transport in vivo (P less than or equal to 0.05; P less than or equal to 0.05). When intestinal BBM vesicles were prepared from birds treated in a manner identical with that described above, there was no observable difference between calcium uptake in BBM vesicles of the 1,25-(OH)2D3-treated birds and that of the cortisol plus 1,25-(OH)2D3-treated birds. 1,25-(OH)2D3-treated and 1,25-(OH)2D3 plus cortisol-treated chicks had intestinal BBM vesicle uptakes that were significantly greater than those of vitamin D-deficient controls (P less than or equal to 0.02; P less than or equal to 0.025). These data show that in vivo intestinal calcium transport may be markedly reduced in the presence of normal intestinal BBM vesicle calcium uptake. This suggest that factors other than BBM calcium uptake (e.g., protein synthesis or contraluminal membrane events) play an important role in the movement of calcium from the intestinal lumen into the bloodstream and extracellular fluid of the organism.

  13. The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium.

    Science.gov (United States)

    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. © 2016 Poultry Science Association Inc.

  14. [Absorption and transport of isoflavonoid compounds from Tongmai formula across human intestinal epithelial (Caco-2) cells in vitro].

    Science.gov (United States)

    Wang, Fu-Rong; Yang, Xiu-Wei

    2017-08-01

    Tongmai formula (TMF) is a drug combination of three components including Puerariae Lobatae Radix [roots of Pueraria lobata], Salviae Miltiorrhizae Radix (roots of Salvia miltiorrhiza) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong) in a weight ratio of 1∶1∶1. The absorption and transport of isoflavonoid compounds from Tongmai formula across human intestinal epithelial (Caco-2) cells in vitro were studied in this paper. The assay isoflavonoid compounds include daidzein, formononetin, 5-hydroxylononin, ononin, daidzin, 3'-methoxypuerarin, genistin, puerarin, formononetin-8-C-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside, formononetin-7-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside, lanceolarin, kakkanin, daidzein-7,4'-di-O-β-D-glucopyranoside, mirificin, 3'-hydroxypuerarin, 3'-methoxydaidzin, formononetin-8-C-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside, genistein-8-C-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside, genistein-7-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (ambocin), 3'-hydroxymirificin, 6″-O-β-D-xylosylpuerarin, biochanin A-8-C-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside, 3'-methoxydaidzein-7,4'-di-O-β-D-glucopyranoside, daidzein-7-O-β-D-glucopyranosyl-(1→4)-O-β-D-glucopyranoside, and daidzein-7-O-α-D-glucopyranosyl-(1→4)-O-β-D-glucopyranoside. By using human Caco-2 monolayer as an intestinal epithelial cell model in vitro, the permeability of above-mentioned 25 isoflavonoids in TMF were studied from the apical (AP) side to basolateral (BL) side or from the BL side to AP side. The assay compounds were determined by reversed phased high-performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apparent permeability coefficients (Papp) were then calculated and and compared with those of propranolol and atenolol, which are the transcellular transport marker and as a control substance for high and poor permeability, respectively. The Papp values of daidzein and

  15. Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester.

    Science.gov (United States)

    Julien-David, Diane; Ennahar, Saïd; Miesch, Michel; Geoffroy, Philippe; Raul, Francis; Aoude-Werner, Dalal; Lessinger, Jean-Marc; Marchioni, Eric

    2009-10-01

    Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC 3.1.1.13) and the liberated sterol may interfere with cholesterol reducing its intestinal absorption. PE-enriched foods are marketed for cooking purposes, and temperature is one of the most important factors leading to the formation of oxidation products. Very little is known about the outcome of PE oxides during the digestive process. A new analytical method based on mass spectrometric detection directly after enzymatic reaction was developed to determine in vitro the activity of CEase on PE and their oxides present in functional food. Using this method, we identified a new inhibitor of CEase: sitosteryl 9,10-dihydroxystearate, which behaves as a non-competitive inhibitor of the hydrolysis of cholesteryl oleate and sitosteryl oleate.

  16. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Science.gov (United States)

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  17. Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats.

    Science.gov (United States)

    Lapphanichayakool, Phakhamon; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip

    2017-01-01

    The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called "sericin-derived oligopeptides" (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg -1  day -1 , 50 mg kg -1  day -1 , and 200 mg kg -1  day -1 ) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet. Triglyceride and HDL-cholesterol levels were not significantly changed among all groups. The fecal contents of bile acids and cholesterol did not differ among high-cholesterol fed rats. SDO dose-dependently reduced cholesterol solubility in lipid micelles, and inhibited cholesterol uptake in monolayer Caco-2 cells. SDO also effectively bound to all three types of bile salts including taurocholate, deoxytaurocholate, and glycodeoxycholate. Direct interaction with bile acids of SDO may disrupt micellar cholesterol solubility, and subsequently reduce the absorption of dietary cholesterol in intestines. Taking all data together, SDO or sericin peptides exhibit a beneficial effect on blood cholesterol levels and could be potentially used as a health-promoting dietary supplement or nutraceutical product.

  18. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    Science.gov (United States)

    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

  19. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    Science.gov (United States)

    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. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Intestinal and Hepatic Niemann-Pick C1-Like 1

    Directory of Open Access Journals (Sweden)

    Sung-Woo Park

    2013-08-01

    Full Text Available Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1 is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, diabetes, and atherosclerosis. In this review, the identification and characterization of NPC1L1, NPC1L1-dependent cholesterol transport, the relationship with pathogenesis of metabolic disease and its newly introduced function for virus entry are discussed.

  1. Micellar lipid composition profoundly affects LXR-dependent cholesterol transport across CaCo2 cells

    NARCIS (Netherlands)

    Petruzzelli, Michele; Groen, Albert K.; van Erpecum, Karel J.; Vrins, Carlos; van der Velde, Astrid E.; Portincasa, Piero; Palasciano, Giuseppe; van Berge Henegouwen, Gerard P.; Sasso, Giuseppe Lo; Morgano, Annalisa; Moschetta, Antonio

    2009-01-01

    Intraluminal phospholipids affect micellar solubilization and absorption of cholesterol. We here study cholesterol transport from taurocholate-phospholipid-cholesterol micelles to CaCo2 cells, and associated effects on ABC-A1 mediated cholesterol efflux. Micellar incorporation of

  2. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  3. Cholesterol Test

    Science.gov (United States)

    ... measures: LDL levels. Also known as the "bad" cholesterol, LDL is the main source of blockages in the ... high 240mg/dL and above High LDL (Bad) Cholesterol Level LDL Cholesterol Category Less than 100mg/dL Optimal 100- ...

  4. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. Comparison of a Computer Simulation Program and a Traditional Laboratory Practical Class for Teaching the Principles of Intestinal Absorption.

    Science.gov (United States)

    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…

  6. Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption

    DEFF Research Database (Denmark)

    Bøgh, Marie; Baldursdóttir, Stefania G; Müllertz, Anette

    2014-01-01

    to establish a more representative in vitro model for the intestinal mucosa. The rheological profile of a biosimilar mucus mixture composed of purified gastric mucin, lipids and protein in buffer was optimized by supplementing with an anionic polymer to display viscoelastic properties and a microstructure...

  7. Effect of soy protein on swine intestinal lipoproteins

    International Nuclear Information System (INIS)

    Ho, H.T.

    1987-01-01

    Hypocholesterolemic effect of soy protein appears to be the result of reduced cholesterol absorption and enhanced cholesterol excretion. The objective of this study is to delineate the underlying mechanism of soy protein effect on cholesterol absorption. At the end of a 5-week soy-protein or casein diet, swine were subjected to cannulation of mesenteric lymph duct under halothane anesthesia. A single dose of 250 μCi [ 14 C]-cholesterol and 10 mCi [ 3 H]-leucine was infused into the upper jejunum two hours after one-fifth of daily food was given. Then lymph was collected hourly for three hours and the lipoprotein fractions were separated by ultracentrifugation. SDS-PAGE (5%) was used to measure the concentrations of individual apoproteins by densitometric scanning. The three-hour lymphatic transport of cholesterol in casein-fed swine was significantly higher than in those fed soy protein. Triglyceride transports were similar in two groups. The [ 3 H]-leucine incorporation study revealed that transport of apo B-48 bore a significant positive relationship to transport of cholesterol in both chylomicron and VLDL fractions of mesenteric lymph. A greater apo B-48 secretion with higher specific activity was probably responsible for the greater transport of cholesterol in chylomicrons in casein-fed swine. On the other hand, the lesser cholesterol transport in chylomicrons in soy protein-fed swine was probably caused by lower apo B-48 secretion. Similarly, the transport of lymph VLDL cholesterol in swine fed casein or soy protein paralleled the amount of accompanying apo B-48. Dietary proteins probably influence the intestinal synthesis of apo B-48 which in turn affects cholesterol transport into the lymphatics

  8. Baicalin pharmacokinetic profile of absorption process using novel in-vitro model: cytochrome P450 3A4-induced Caco-2 cell monolayers combined with rat intestinal rinse fluids.

    Science.gov (United States)

    Morisaki, Tomoko; Hou, Xiao-Long; Takahashi, Kyoko; Takahashi, Koichi

    2013-10-01

    This study was designed to investigate baicalin (BG) pharmacokinetic profile in absorption process using a new model and evaluate the potentiality as a new model. The effects of BG on intestinal cytochrome P450 3A4 (CYP3A) protein/mRNA expression, activity and permeability glycoprotein (P-gp) were evaluated in CYP3A4-induced Caco-2 cell monolayers or rats. Intestinal rinse fluids (IF) were obtained from rat were added to modified Caco-2 monolayers. Orally administered BG (7 days pretreatment) inhibited intestinal CYP3A activity and protein expression. Baicalein (B) converted from BG by IF was detected in the upper jejunum in a portion-dependent manner. Subsequently, most BG were converted to B in the caecum. In modified Caco-2 monolayers, BG exhibited no effect on CYP3A4 activity or mRNA, whereas B and BG treated with IF inhibited CYP3A4 transcription and activity. Intestinal CYP3A was inhibited following oral administration of BG to rat. Correspondingly, BG-mediated CYP3A inhibition was shown in vitro using modified Caco-2 monolayers treated with IF. Hence, in-vivo intestinal absorption pharmacokinetic was reproduced in vitro. IF is a key determinant of intestinal absorption, and it facilitated inhibition of CYP3A by B, not BG. © 2013 Royal Pharmaceutical Society.

  9. 3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

    International Nuclear Information System (INIS)

    Saint, C.; Gallo, I.; Kantorow, M.; Bailey, J.M.

    1986-01-01

    Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14 C-cholesteryl oleate with an I 50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

  10. Study of Absorption Characteristics of the Total Saponins from Radix Ilicis Pubescentis in an In Situ Single-Pass Intestinal Perfusion (SPIP Rat Model by Using Ultra Performance Liquid Chromatography (UPLC

    Directory of Open Access Journals (Sweden)

    Guojun Kuang

    2017-11-01

    Full Text Available In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ. This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1, ilexsaponin A1 (C2, ilexsaponin B1 (C3, ilexsaponin B2 (C4, ilexsaponin B3 (DC1, and ilexoside O (DC2 when administrated with the total saponins from MDQ (MDQ-TS. An UPLC method for simultaneous determination of C1, C2, C3, C4, DC1, and DC2 in intestinal outflow perfusate was developed and validated. The absorption characteristics of MDQ-TS were investigated by evaluating the effects of intestinal segments, drug concentration, P-glycoprotein (P-gp inhibitor (verapomil, endocytosis inhibitor (amantadine and ethylene diamine tetraacetic acid (EDTA, tight junction modulator on the intestinal transportation of MDQ-TS by using a single-pass intestinal perfusion (SPIP rat model, and the influence of co-existing components on the intestinal transport of the six saponins was discussed. The results showed that effective apparent permeability (Papp of C1, C2, C3, C4, and DC2 administrated in MDQ-TS form had no segment-dependent changes at low and middle dosage levels. C1, C2, C3, D4, DC1, and DC2 administrated in MDQ-TS form all exhibited excellent transmembrane permeability with Papp > 0.12 × 10−2 cm·min−1. Meanwhile, Papp and effective absorption rate constant (Ka values for the most saponins showed concentration dependence and saturation characteristics. After combining with P-gp inhibitor of verapamil, Papp of C2, C3, and DC1 in MDQ-TS group was significantly increased up to about 2.3-fold, 1.4-fold, and 3.4-fold, respectively in comparison to that of non-verapamil added group. Verapamil was found to improve the absorption of C2, C3, and DC1, indicating the involvement of an active transport mechanism in the absorption process. Compared with the

  11. Absorção de anticorpos do colostro em bezerros: I. Estudo no intestino delgado proximal Colostral antibodies absorption in dairy calves: I. Proximal small intestine study

    Directory of Open Access Journals (Sweden)

    Rosana Bessi

    2002-11-01

    Full Text Available Com o objetivo de estudar a morfologia e determinar a localização da enzima fosfatase ácida na região anterior do intestino delgado, do nascimento ao fechamento intestinal, foram coletadas amostras de 15 bezerros machos em três idades: ao nascer sem que houvesse a ingestão de colostro; três horas após a ingestão da primeira refeição de colostro e aos três dias de idade. Observou-se a presença de células vacuoladas do duodeno ao jejuno médio no recém-nascido, preenchidas por material absorvido após a ingestão de colostro. Foram verificadas mudanças nas características morfológicas aos três dias de idade, com o início da detecção de reação da fosfatase ácida em lisossomos, indicando ação enzimática sobre o material absorvido. A morfologia aos três dias de idade pode representar o diferente estádio de maturação das células epiteliais do intestino delgado de bezerros, indicando que o processo depende das características da primeira geração de células desta região do intestino.The objective of this study was to study the morphology and the localization of acid phosphatase at calves anterior small intestine, from birth to intestinal closure. Fifteen male dairy calves were used in this study, which were aged: unsuckled neonatal, three hours after colostrum ingestion and three days old. Vacuolated cells from duodenum to medium jejunum could be found in the newborn calf, which have shown absorbed material after colostrum ingestion. Changes at the morphological characteristics and the initiation of phosphatase acid reaction in lysosomes were observed in calves aged three days old. The three days old morphology can represent a different phase of epithelium cells maturation of calves small intestine indicating that the absorption process is dependent of the first generation of cells from this intestinal region.

  12. Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis.

    Science.gov (United States)

    Uenishi, K; Tokiwa, M; Kato, S; Shiraki, M

    2018-03-01

    Intestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH) 2 D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine. To assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted. Forty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 μg/day), 1α hydroxyl calcidiol (ALF; 1 μg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured. The baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH) 2 D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations. These findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate

  13. Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Bloks, VW; Bakker-van Waarde, WM; Verkade, HJ; Kema, IP; Wolters, H; Vink, E; Groen, AK; Kuipers, F

    Aim/hypothesis., Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both

  14. Dietary Wheat Bran Oil Is Equally as Effective as Rice Bran Oil in Reducing Plasma Cholesterol.

    Science.gov (United States)

    Lei, Lin; Chen, Jingnan; Liu, Yuwei; Wang, Lijun; Zhao, Guohua; Chen, Zhen-Yu

    2018-03-21

    Rice bran oil (RBO) possesses a plasma cholesterol-lowering activity, while effect of wheat bran oil (WBO) on plasma cholesterol remains unknown. The present study compared the cholesterol-lowering activity of WBO with that of RBO in hamsters. Fifty-four male hamsters were divided into seven groups fed either a noncholesterol diet (NCD) or one of six high-cholesterol diets, namely HCD diet (0.2% cholesterol +9.5% lard), HCD+C diet (0.2% cholesterol +9.5% lard +0.5% cholestyramine), WL diet (0.2% cholesterol +4.8% Lard +4.8% WBO), WH diet (0.2% cholesterol +9.5% WBO), RL diet (0.2% cholesterol +4.8% Lard +4.8% RBO), and RH diet (0.2% cholesterol +9.5% RBO). Plasma total cholesterol (TC) in HCD group was 327.4 ± 31.8 mg/dL, while plasma TC in two WBO and two RBO groups was 242.2 ± 20.8, 243.1 ± 31.7, 257.1 ± 16.3, and 243.4 ± 46.0 mg/dL, respectively, leading to a decrease in plasma TC by 22-26% ( P cholesterol-lowering potency was seen between WBO and RBO. Plasma cholesterol-lowering activity of WBO and RBO was accompanied by down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase, while up-regulation of cholesterol-7α-hydroxylase. WL, WH, RL, and RH diets increased the fecal excretion of total neutral sterols by 72.8%, 106.9%, 5.4%, and 36.8% ( P cholesterol absorption via down-regulation of intestinal Niemann-Pick C1 like 1 protein, acyl CoA:cholesterol acyltransferase 2, and ATP binding cassette transporter 5. In summary, WBO was equally effective as RBO in decreasing plasma cholesterol in hypercholesterolemia hamsters.

  15. 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.

    Science.gov (United States)

    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. © 2013.

  16. Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans.

    Science.gov (United States)

    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. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats

    International Nuclear Information System (INIS)

    Pavelka, M.; Gangl, A.

    1983-01-01

    The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, researchers have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [ 14 C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that colchicine causes significant changes in enterocyte ultrastructure and colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte

  18. Bile Acid-regulated Peroxisome Proliferator-activated Receptor-α (PPARα) Activity Underlies Circadian Expression of Intestinal Peptide Absorption Transporter PepT1/Slc15a1*

    Science.gov (United States)

    Okamura, Ayako; Koyanagi, Satoru; Dilxiat, Adila; Kusunose, Naoki; Chen, Jia Jun; Matsunaga, Naoya; Shibata, Shigenobu; Ohdo, Shigehiro

    2014-01-01

    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. PMID:25016014

  19. Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1.

    Science.gov (United States)

    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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Effects of a 2-y dietary weight-loss intervention on cholesterol metabolism in moderately obese men.

    Science.gov (United States)

    Leichtle, Alexander B; Helmschrodt, Christin; Ceglarek, Uta; Shai, Iris; Henkin, Yaakov; Schwarzfuchs, Dan; Golan, Rachel; Gepner, Yftach; Stampfer, Meir J; Blüher, Matthias; Stumvoll, Michael; Thiery, Joachim; Fiedler, Georg M

    2011-11-01

    Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear. We assessed the effects of 2 y of weight loss achieved with various diet regimens on phytosterols (markers of intestinal cholesterol absorption), lanosterol (marker of de novo cholesterol synthesis), and changes in apolipoprotein concentrations. We conducted the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low-carbohydrate diets). We assessed circulating phytosterol and lanosterol concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100 in 90 DIRECT participants at 0, 6, and 24 mo. We observed a significant upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P weight-loss phase (first 6 mo, weight loss of 5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL cholesterol continuously increased during the study (17.0%, P weight loss is related to a characteristic response suggestive of altered cholesterol and apolipoprotein metabolism. Various diets have a similar effect on these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.

  1. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

    Science.gov (United States)

    Racette, Susan B; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

  2. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

    Science.gov (United States)

    Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (−8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (−5.0 ± 2.1%; P = 0.077). Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054. PMID:19889819

  3. Influence of the Gut Microflora and of Biliary Constituents on Morphological Changes in the Small Intestine in Obstructive Jaundice

    Directory of Open Access Journals (Sweden)

    M. Saeed Quraishy

    1996-01-01

    Full Text Available Increased amounts of intestinal endotoxin are absorbed in obstructive jaundice. The precise mechanism is not known but the increased absorption may arise from alterations in the luminal contents, in the intestinal flora, in the gut wall or in interactions between all three. To examine the effects of the intestinal flora we have compared the morphological changes in the small intestine in obstructive jaundice in germ free and conventional rats while the effects of bile constituents have been examined by addition of bile constituents to the diet of bile duct ligated rats. Changes in the intestine were examined, histologically, by enzyme histochemistry, and by transmission and scanning electron microscopy. The results showed no differences in response between germ free and conventional rats. Feeding of diets containing bile salts exacerbated the lesion. Feeding of diets containing cholesterol, however, reduced the degree of intestinal changes produced by cholestasis and completely antagonised the increase in damage caused by feeding of bile salts.

  4. Acupuncture Improves Intestinal Absorption of Iron in Iron-deficient Obese Patients: A Randomized Controlled Preliminary Trial

    OpenAIRE

    Xin-Cai Xie; Yan-Qiang Cao; Qian Gao; Chen Wang; Man Li; Shou-Gang Wei

    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 Traditi...

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

    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

  6. 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

    International Nuclear Information System (INIS)

    Yang, Cuiping; Zhang, Tianhong; Li, Zheng; Xu, Liang; Liu, Fei; Ruan, Jinxiu; Liu, Keliang; Zhang, Zhenqing

    2013-01-01

    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 (C 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 0–12 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 max and AUC of aconitine. • P

  7. Absorção de anticorpos do colostro em bezerros: II. Estudo no intestino delgado distal Colostral antibodies absorption in calves: II. Distal small intestine

    Directory of Open Access Journals (Sweden)

    Rosana Bessi

    2002-11-01

    Full Text Available Com o objetivo de estudar a morfologia e determinar a localização da enzima fosfatase ácida na região distal do intestino delgado de bezerros, do nascimento ao fechamento intestinal, foram coletadas amostras de 15 animais machos em três idades: ao nascer sem que houvesse a ingestão de colostro; três horas após a ingestão da primeira refeição de colostro e aos três dias de idade. Observou-se, ao nascimento, a presença de um grande vacúolo, que dominava todo o citoplasma das células epiteliais do jejuno distal e íleo. Após a ingestão de colostro, verificou-se o acúmulo de material absorvido nesses vacúolos. Foi detectada a reação de fosfatase ácida nas células absortivas de bezerros recém-nascidos, antes e após a ingestão de colostro. Aos três dias de idade, uma nova população de células geralmente não vacuoladas, com sistema endocítico apical reduzido, foi observada recobrindo as vilosidades intestinais. Portanto, em bezerros a maturação do epitélio absortivo do intestino delgado distal pode iniciar-se com o aumento da atividade enzimática nos vacúolos absortivos, culminando com a rápida substituição das células fetais por células diferenciadas não pinocíticas, o que determinaria o término da transferência de anticorpos maternos.The localization of acid phosphatase at distal small intestine and its morphology were studied f0rom birth to intestinal closure from fifteen male dairy calves aged: unsuckled neonatal, three hours after colostrum ingestion and three days old. At birth, the presence of a large vacuole was found and it expanded all over the epithelial cells cytoplasm at distal jejunum and ileum. For colostrum fed calves, ingested material could be observed in the vacuole. The phosphatase acid reaction was detected in the absorptive cells of suckled and unsuckled newborn calves. Calves aged three days old, a new population of non-vacuolated cells and reduced apical endocytic system were found

  8. Ontogeny, growth and development of the small intestine: Understanding pediatric gastroenterology.

    Science.gov (United States)

    Drozdowski, Laurie A; Clandinin, Tom; Thomson, Alan B R

    2010-02-21

    Throughout our lifetime, the intestine changes. Some alterations in its form and function may be genetically determined, and some are the result of adaptation to diet, temperature, or stress. The critical period programming of the intestine can be modified, such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother, or in the diet of the weanlings. This early forced adaptation may persist in later life, such as the unwanted increased intestinal absorption of sugars, fatty acids and cholesterol. Thus, the ontogeny, early growth and development of the intestine is important for the adult gastroenterologist to appreciate, because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.

  9. Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-04-01

    To investigate the potential interaction between grapefruit juice (GFJ) and the oral microtubule polymerization inhibitor colchicine, a P-gp and CYP3A4 substrate. Colchicine intestinal epithelial transport was investigated across Caco-2 cell monolayers in both AP-BL and BL-AP directions, in the absence/presence of known P-gp inhibitors (verapamil and quinidine). The concentration-dependent effects of GFJ and its major constituents (6'-7'-dihydroxybergamottin, naringin and naringenin) on colchicine Caco-2 mucosal secretion were examined. The effect of GFJ on colchicine intestinal-permeability was then investigated in-situ in the rat perfusion model, in both jejunum and ileum. Colchicine exhibited 20-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion, which was reduced by verapamil/quinidine. Colchicine AP-BL permeability was increased and BL-AP was decreased by GFJ in a concentration-dependent manner (IC(50) values of 0.75% and 0.46% respectively), suggesting inhibition of efflux transport, rather than metabolizing enzyme. Similar effects obtained following pre-experiment incubation with GFJ, even though the juice was not present throughout the transepithelial study. 6'-7'-Dihydroxybergamottin, naringin and naringenin displayed concentration-dependent inhibition on colchicine BL-AP secretion (IC(50) values of 90, 592 and 11.6 microM respectively). Ten percent GFJ doubled colchicine rat in-situ ileal permeability, and increased 1.5-fold jejunal permeability. The data suggest that GFJ may augment colchicine oral bioavailability. Due to colchicine narrow therapeutic-index and severely toxic side-effects, awareness of this interaction is prudent.

  10. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  11. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

    Science.gov (United States)

    2011-01-01

    Background To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. Methods and Results The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. Conclusion We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms. PMID:22018353

  12. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets.

    Science.gov (United States)

    Thacher, Tom D; Obadofin, Michael O; O'Brien, Kimberly O; Abrams, Steven A

    2009-09-01

    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 nutritional rickets. The participants were randomized to 1.25 mg oral vitamin D(3) (n = 8) or vitamin D(2) (n = 9). Fractional calcium absorption 3 da after vitamin D administration was measured. Mean baseline 25-hydroxyvitamin D concentrations were 20 ng/ml (range 5-31 ng/ml). The increase in 25-hydroxyvitamin D was equivalent after vitamin D(3) (29 +/- 10 ng/ml) or vitamin D(2) (29 +/- 17 ng/ml). Mean 1,25-dihydroxyvitamin D values increased from 143 +/- 76 pg/ml to 243 +/- 102 pg/ml (P = 0.001), and the increase in 1,25-dihydroxyvitamin D did not differ between vitamin D(2) and vitamin D(3) (107 +/- 110 and 91 +/- 102 ng/ml, respectively). The increment in 1,25-dihydroxyvitamin D was explained almost entirely by the baseline 25-hydroxyvitamin D concentration (r(2) = 0.72; P rickets in Nigerian children is not primarily due to vitamin D-deficient calcium malabsorption.

  13. Absorption, Conjugation and Efflux of the Flavonoids, Kaempferol and Galangin, Using the Intestinal CACO-2/TC7 Cell Model.

    Science.gov (United States)

    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.

  14. Statistical modelling coupled with LC-MS analysis to predict human upper intestinal absorption of phytochemical mixtures.

    Science.gov (United States)

    Selby-Pham, Sophie N B; Howell, Kate S; Dunshea, Frank R; Ludbey, Joel; Lutz, Adrian; Bennett, Louise

    2018-04-15

    A diet rich in phytochemicals confers benefits for health by reducing the risk of chronic diseases via regulation of oxidative stress and inflammation (OSI). For optimal protective bio-efficacy, the time required for phytochemicals and their metabolites to reach maximal plasma concentrations (T max ) should be synchronised with the time of increased OSI. A statistical model has been reported to predict T max of individual phytochemicals based on molecular mass and lipophilicity. We report the application of the model for predicting the absorption profile of an uncharacterised phytochemical mixture, herein referred to as the 'functional fingerprint'. First, chemical profiles of phytochemical extracts were acquired using liquid chromatography mass spectrometry (LC-MS), then the molecular features for respective components were used to predict their plasma absorption maximum, based on molecular mass and lipophilicity. This method of 'functional fingerprinting' of plant extracts represents a novel tool for understanding and optimising the health efficacy of plant extracts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Folate absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Folate is the generic term given to numerous compounds of pteroic acid with glutamic acid. Knowledge of absorption is limited because of the complexities introduced by the variety of compounds and because of the inadequacy of investigational methods. Two assay methods are in use, namely microbiological and radioactive. Techniques used to study absorption include measurement of urinary excretion, serum concentration, faecal excretion, intestinal perfusion, and haematological response. It is probably necessary to test absorption of both pteroylmonoglutamic acid and one or more polyglutamates, and such tests would be facilitated by availability of synthesized compounds labelled with radioactive tracers at specifically selected sites. (author)

  16. Effect of partially hydrolyzed guar gum (PHGG) on the bioaccessibility of fat and cholesterol.

    Science.gov (United States)

    Minekus, Mans; Jelier, Mark; Xiao, Jin-Zhong; Kondo, Shizuki; Iwatsuki, Keiji; Kokubo, Sadayuki; Bos, Martin; Dunnewind, Bertus; Havenaar, Robert

    2005-05-01

    The addition of a compound that lowers the intestinal uptake of fat and cholesterol might be an interesting strategy to reduce the risk of vascular disease. Partially hydrolyzed guar gum (PHGG) has been shown to have this effect in healthy volunteers after intake of a yogurt drink with 3 to 6% PHGG. In the present study a yogurt drink with 3% sunflower oil and 4% egg yolk was tested with 3% and 6% PHGG, and compared to a control without PHGG. Experiments were performed in a multi-compartmental model of the gastrointestinal tract, equipped to study the digestion and availability for absorption (bioaccessibility) of lipids. The results show that PHGG decreases the bioaccessibility of both fat and cholesterol in a dose-dependent manner. The bioaccessibility of fat was 79.4+/-1.7%, 70.8+/-2.5% and 60.1+/-1.1% for the control experiments and the experiments with 3% and 6% PHGG respectively. The bioaccessibility of cholesterol was 82.2+/-2.0%, 75.4+/-1.2% and 64.0+/-4.3% for the control and the experiments with 3% and 6% PHGG respectively. Additional experiments indicated that PHGG reduces bioaccessibility through the depletion flocculation mechanism. Depletion flocculation antagonizes the emulsification by bile salts and thus decreases lipolytic activity, resulting in a lower bioaccessibility of fat and cholesterol. Depletion flocculation with polymers might be an interesting mechanism, not described before, to reduce fat and cholesterol absorption.

  17. Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

    Science.gov (United States)

    Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

    2010-08-02

    Antiviral 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 antiviral agents zanamivir 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-naphthoic 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 (K(11(aq))) 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 (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 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 P(app) 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 (P(eff)) 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 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) 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

  18. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  19. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  20. HDL: The "Good" Cholesterol

    Science.gov (United States)

    ... There are two main types of cholesterol: HDL (good) cholesterol and LDL (bad) cholesterol: HDL stands for high-density lipoproteins. It is called the "good" cholesterol because it carries cholesterol from other parts ...

  1. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  2. N-terminal domain of the cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) is essential for α-tocopherol transport.

    Science.gov (United States)

    Kamishikiryo, Jun; Haraguchi, Misaki; Nakashima, Shunsuke; Tasaka, Yuka; Narahara, Hiroe; Sugihara, Narumi; Nakamura, Tetsuya; Morita, Tetsuo

    2017-04-29

    Both cholesterol and α-tocopherol are essential lipoph