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

1977 ◽  
Vol 232 (5) ◽  
pp. E471 ◽  
Author(s):  
D Hollander ◽  
K S Muralidhara
Keyword(s):  
Intestinal Absorption ◽  
Absorption Rate ◽  
Sodium Taurocholate ◽  
Water Layer ◽  
Metabolic Inhibitors ◽  
Absorption Mechanism ◽  
Lymphatic Circulation ◽  
Passive Absorption

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

Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport.

1977 ◽  
Vol 232 (1) ◽  
pp. E69 ◽  
Author(s):  
D Hollander ◽  
E Rim ◽  
K S Muralidhara
Keyword(s):  
Intestinal Absorption ◽  
Absorption Rate ◽  
Saturated Fatty Acids ◽  
Sodium Taurocholate ◽  
Water Layer ◽  
Vitamin K1 ◽  
Unstirred Water Layer ◽  
Saturation Kinetics ◽  
Nonionic Detergent

Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.

scholarly journals In vivo and in vitro study on characterization and mechanism of the intestinal absorption of 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside

2019 ◽  
Author(s):  
Cheng Wang ◽  
Yimeng Zhou ◽  
Xiaohong Gong ◽  
Li Zheng ◽  
Yunxia Li
Keyword(s):  
Intestinal Absorption ◽  
High Performance ◽  
Cell Monolayer ◽  
In Vitro Study ◽  
Absorption Mechanism ◽  
Pharmacological Activities ◽  
Concentration Time ◽  
Basic Parameters

Abstract Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibits a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound has poor bioavailability and the underlying absorption mechanisms has not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods: This study used the Caco-2 cell monolayer model and the single-passintestinal perfusion modelto explore the intestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.In addition, the susceptibility of TSG absorption process to treatment with three inhibitors, such as P-gp inhibitors verapamil hydrochloride and quinidine, and the MRP2 inhibitor probenecid were also assessed. Results: TSG is poorly absorbed in the intestines and the absorption of TSG in the stomach is much higher than that in the intestine. Both in vivo and in vitro experiments showed that the absorption of TSG was saturated with increasing concentration. and it was better absorbed in a weakly acidic environment with a pH of 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG is not only the substrate of the P-gp and MRP2, but also affects the expression of P-gp and MRP2. Conclusions: It can be concluded that the intestinal absorption mechanismsofTSG involve processes passive transport and the participation of efflux transporters.

Alpha-lactalbumin Effect on Myo-inositol Intestinal Absorption: In vivo and In vitro

2018 ◽  
Vol 15 (9) ◽  
pp. 1305-1311 ◽  
Author(s):  
Giovanni Monastra ◽  
Yula Sambuy ◽  
Simonetta Ferruzza ◽  
Daniela Ferrari ◽  
Giulia Ranaldi
Keyword(s):  
Intestinal Absorption ◽  
Intestinal Absorption In Vivo ◽  
Alpha Lactalbumin

In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling

2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
In Silico ◽  
Review Paper ◽  
Cell Monolayer ◽  
Cell Permeability ◽  
Drug Substances ◽  
Wide Range ◽  
Modeling Techniques

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

scholarly journals New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 595
Author(s):  
Norraseth Kaeokhamloed ◽  
Emillie Roger ◽  
Jérôme Béjaud ◽  
Nolwenn Lautram ◽  
Florence Manero ◽  
...  
Keyword(s):  
Surface Modification ◽  
Intestinal Absorption ◽  
Oral Absorption ◽  
Membrane Integrity ◽  
Microvascular Endothelial Cell ◽  
Absorption Mechanism ◽  
Apparent Permeability ◽  
Lipid Nanocapsules ◽  
Coculture Model

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell® insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes. Lipid nanocapsules (LNCs) were formulated with different sizes (55 and 85 nm) and surface modifications (DSPE-mPEG (2000) and stearylamine). Nanocapsule integrity and particle concentration were monitored using the Förster resonance energy transfer (FRET) technique. The result showed that surface modification by DSPE-mPEG (2000) increased the absorption of 55-nm LNCs in the coculture model but not in the Caco-2. Summarily, the coculture model was validated as a tool for evaluating the intestinal absorption of drugs and nanoparticles. The new coculture model has a different LNCs absorption mechanism suggesting the importance of intestinal endothelium and reveals that the surface modification of LNCs can modify the in vitro oral absorption.

Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies

2012 ◽  
Vol 33 (5) ◽  
pp. 246-256 ◽  
Author(s):  
Bilal S. Abuasal ◽  
Hisham Qosa ◽  
Paul W. Sylvester ◽  
Amal Kaddoumi
Keyword(s):  
Intestinal Absorption ◽  
In Vivo Studies

In vitro and in vivo effects of morin on the intestinal absorption and pharmacokinetics of olmesartan medoxomil solid dispersions

2016 ◽  
Vol 43 (5) ◽  
pp. 812-829 ◽  
Author(s):  
Gurunath Surampalli ◽  
Madhuchander Satla ◽  
Basavaraj K. Nanjwade ◽  
Paragouda A. Patil
Keyword(s):  
Intestinal Absorption ◽  
Solid Dispersions ◽  
Olmesartan Medoxomil ◽  
In Vivo Effects

Role of mesenteric lymphatic system in water absorption from rat intestine in vitro

1963 ◽  
Vol 204 (1) ◽  
pp. 92-96 ◽  
Author(s):  
J. S. Lee
Keyword(s):  
Water Absorption ◽  
Absorption Rate ◽  
Lymphatic System ◽  
Average Frequency ◽  
Rat Intestine ◽  
Isolated Segment ◽  
Rhythmical Contractions

With an in vitro rat jejunal preparation it was found that at low distention pressures the absorption rate of segments without mesentery are about 40% lower than the rate of those with intact mesentery. The decrease of absorption rate in segments with lacteal ducts sectioned near the gut wall was the same as the rate for those completely devoid of mesentery. Section of blood vessels showed no decrease but rather a slight increase in rate. The mesenteric lymphatic ducts during water absorption in vitro and in vivo showed rhythmical contractions with an average frequency of 10/min. The lymphatic ducts of an isolated mesentery may continue to contract and transport water for a few minutes. The lymphatic pressure of the isolated segment is assumed to be an approximate measure of absorbing force. Epinephrine may augment lymphatic contractility and may also elevate lymphatic pressure. These observations suggest that the mesenteric lymphatics may play a significant role in water transport.

Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart

2005 ◽  
Vol 288 (5) ◽  
pp. H2412-H2421 ◽  
Author(s):  
Markus Frederich ◽  
Li Zhang ◽  
James A. Balschi
Keyword(s):  
Protein Kinase ◽  
Metabolic Inhibitors ◽  
Protein Kinase Activity ◽  
Α Subunit ◽  
Rat Hearts ◽  
Upstream Kinase ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The hypothesis was tested that hypoxia increases AMP-activated protein kinase (AMPK) activity independently of AMP concentration ([AMP]) in heart. In isolated perfused rat hearts, cytosolic [AMP] was changed from 0.2 to 16 μM using metabolic inhibitors during both normal oxygenation (95% O2-5% CO2, normoxia) and limited oxygenation (95% N2-5% CO2, hypoxia). Total AMPK activity measured in vitro ranged from 2 to 40 pmol·min−1·mg protein−1 in normoxic hearts and from 5 to 55 pmol·min−1·mg protein−1 in hypoxic hearts. The dependence of the in vitro total AMPK activity on the in vivo cytosolic [AMP] was determined by fitting the measurements from individual hearts to a hyperbolic equation. The [AMP] resulting in half-maximal total AMPK activity ( A0.5) was 3 ± 1 μM for hypoxic hearts and 28 ± 13 μM for normoxic hearts. The A0.5 for α2-isoform AMPK activity was 2 ± 1 μM for hypoxic hearts and 13 ± 8 μM for normoxic hearts. Total AMPK activity correlated with the phosphorylation of the Thr172 residue of the AMPK α-subunit. In potassium-arrested hearts perfused with variable O2 content, α-subunit Thr172 phosphorylation increased at O2 ≤ 21% even though [AMP] was <0.3 μM. Thus hypoxia or O2 ≤ 21% increased AMPK phosphorylation and activity independently of cytosolic [AMP]. The hypoxic increase in AMPK activity may result from either direct phosphorylation of Thr172 by an upstream kinase or reduction in the A0.5 for [AMP].

Sign in / Sign up

Export Citation Format

Share Document