scholarly journals Energy-Dependent Endocytosis is Involved in the Absorption of Indomethacin Nanoparticles in the Small Intestine

2019 ◽  
Vol 20 (3) ◽  
pp. 476 ◽  
Author(s):  
Miyu Ishii ◽  
Yuya Fukuoka ◽  
Saori Deguchi ◽  
Hiroko Otake ◽  
Tadatoshi Tanino ◽  
...  
Keyword(s):  
Small Intestine ◽  
Intestinal Epithelium ◽  
Cytochalasin D ◽  
Therapeutic Effects ◽  
Rat Intestine ◽  
Drug Nanoparticles ◽  
Oral Formulations ◽  
Basolateral Side ◽  
Energy Dependent ◽  
High Bioavailability

We previously reported that oral formulations containing indomethacin nanoparticles (IND-NPs) showed high bioavailability, and, consequently, improved therapeutic effects and reduced injury to the small intestine. However, the pathway for the transintestinal penetration of nanoparticles remained unclear. Thus, in this study, we investigated whether endocytosis was related to the penetration of IND-NPs (72.1 nm) using a transcell set with Caco-2 cells or rat intestine. Four inhibitors of various endocytosis pathways were used [nystatin, caveolae-dependent endocytosis (CavME); dynasore, clathrin-dependent endocytosis (CME); rottlerin, macropinocytosis; and cytochalasin D, phagocytosis inhibitor], and all energy-dependent endocytosis was inhibited at temperatures under 4 °C in this study. Although IND-NPs showed high transintestinal penetration, no particles were detected in the basolateral side. IND-NPs penetration was strongly prevented at temperatures under 4 °C. In experiments using pharmacological inhibitors, only CME inhibited penetration in the jejunum, while in the ileum, both CavME and CME significantly attenuated penetration. In conclusion, we found a novel pathway for the transintestinal penetration of drug nanoparticles. Our hypothesis was that nanoparticles would be taken up into the intestinal epithelium by endocytosis (CME in jejunum, CavME and CME in ileum), and dissolved and diffused in the intestine. Our findings are likely to be of significant use for the development of nanomedicines.

Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation

1988 ◽  
Vol 254 (5) ◽  
pp. G768-G774 ◽  
Author(s):  
D. A. Parks ◽  
T. K. Williams ◽  
J. S. Beckman
Keyword(s):  
Small Intestine ◽  
Oxygen Radicals ◽  
Total Activity ◽  
Xanthine Dehydrogenase ◽  
Oxygen Radical ◽  
Morphological Evidence ◽  
Cellular Injury ◽  
Rat Intestine ◽  
Entire Small Intestine ◽  
Ischemic Intestine

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.

Some species differences in the intrinsic factor stimulation of B12 uptake by small intestine in vitro

1959 ◽  
Vol 197 (4) ◽  
pp. 926-928 ◽  
Author(s):  
T. Hastings Wilson ◽  
Elliott W. Strauss
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Species Differences ◽  
Intrinsic Factor ◽  
Vitamin B ◽  
Guinea Pig Ileum ◽  
Rat Intestine ◽  
Intrinsic Factors ◽  
Stimulation Of

Sacs of everted small intestine from a variety of animals were incubated in bicarbonate-saline containing vitamin B12 with and without intrinsic factor (IF). B12 uptake by rat intestine was stimulated only by its own intrinsic factor. Guinea pig ileum responded to all intrinsic factors tested (guinea pig, rat, hog, hamster, human being and rabbit). The intestines of hamster and rabbit were intermediate in specificity, responding to some, but not all, of the IF preparations. Species differences occur in both the intestine and intrinsic factor preparations. The guinea pig ileum was suggested as a possible assay for both hog and human IF.

Mucosal mast cells are involved in CCK disruption of MMC in the rat intestine

1998 ◽  
Vol 275 (1) ◽  
pp. G63-G67 ◽  
Author(s):  
Carme Juanola ◽  
Magda Giralt ◽  
Marcel Jiménez ◽  
Marisabel Mourelle ◽  
Patri Vergara
Keyword(s):  
Mast Cell ◽  
Small Intestine ◽  
Mast Cells ◽  
Control Group ◽  
Rat Intestine ◽  
Pancreatic Acini ◽  
Mast Cell Stabilizer ◽  
Mucosal Mast Cells ◽  
Stimulation Of ◽  
Cck Release

Our aim was to determine if mucosal mast cells could be activated by endogenous CCK and, as a consequence, mediate CCK actions in the small intestine. Rats were prepared for electromyography to record electrical activity in the small intestine. In another group of animals, the duodenum was perfused to measure rat mast cell protease II (RMCP II) as indicative of mast cell degranulation. Endogenous CCK release was induced by administration of soybean trypsin inhibitor (SBTI) in conscious rats or by intraduodenal perfusion of ovalbumin hydrolysate (OVH) in anesthetized rats. CCK concentration was measured by bioassay on pancreatic acini. SBTI in control rats disrupted migrating motor complexes (MMC) for >40 min. In rats treated with the mast cell stabilizer ketotifen, SBTI did not induce any change in the MMC pattern. RMCP II concentration in the duodenal perfusate significantly increased after OVH. Perfusate from ketotifen-treated animals did not show any significant increase in RMCP II values during OVH perfusion, although CCK plasma concentration was not different from the control group. Furthermore, infusion of the CCK-B receptor antagonist L-365,260 significantly blocked the increase of RMCP II concentration after OVH. Our results indicate that mucosal mast cells are degranulated by endogenous CCK release through stimulation of CCK-B receptors. Therefore mucosal mast cells participate in CCK intestinal actions.

scholarly journals A low-temperature method for the isolation of small-intestinal epithelium along the crypt-villus axis

1991 ◽  
Vol 280 (2) ◽  
pp. 331-334 ◽  
Author(s):  
N Flint ◽  
F L Cove ◽  
G S Evans
Keyword(s):  
Small Intestine ◽  
Low Temperature ◽  
Intestinal Epithelium ◽  
Sequential Fractionation ◽  
Potential Value ◽  
Temperature Method ◽  
Small Intestinal ◽  
The Comparative Study ◽  
Cell Phenotypes ◽  
Proliferative Cell

A variety of enzymic and non-enzymic methods to isolate epithelium from the small intestine have been previously published. Sequential fractionation of cells from the villus to the crypt has been reported in some of these papers, which allows the comparative study of terminally differentiated and proliferative cell phenotypes. However, these methods often involve the incubation of tissues at 37 degrees C, which may affect the structural and biochemical integrity of the cells. We have developed a rapid low-temperature (4 degrees C) method for isolating purified populations of crypt and villus cells from mouse and rat intestines. The fractionated cells have been partially characterized, and the potential value of the procedure has been indicated by the ability to analyse the comparative protein and mRNA expression along the crypt-villus axis.

Expression of ENaC and serum- and glucocorticoid-induced kinase 1 in the rat intestinal epithelium

2004 ◽  
Vol 286 (4) ◽  
pp. G663-G670 ◽  
Author(s):  
Tatjana Coric ◽  
Nelmary Hernandez ◽  
Diego Alvarez de la Rosa ◽  
Deren Shao ◽  
Tong Wang ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Temporal Relationship ◽  
Distal Tubule ◽  
Distal Colon ◽  
Differential Regulation ◽  
Dependent Manner ◽  
Sodium Depletion ◽  
Rat Intestine ◽  
Sodium Transporters ◽  
Relationship Of

Increase in epithelium sodium channel (ENaC) activity induced by aldosterone in the distal tubule of the kidney has been attributed to serum- and glucocorticoid-induced kinase 1 (sgk1). The distal colon constitutes another classical aldosterone-responsive epithelium that expresses both ENaC and sgk1 in an aldosterone-dependent manner. However, the site of expression and the temporal relationship of the aldosterone induction of these two proteins have not been investigated. Here, we examined the distribution and abundance of sgk1 in the rat intestine under basal conditions and after changes in the concentration of aldosterone and glucocorticoids. Results indicate that sgk1 is expressed in the distal colon and also in the ileum and jejunum. Abundance of sgk1 was high in control animals, and it did not change significantly after sodium depletion or after a single dose of aldosterone; however, it decreased after adrenalectomy. In contrast, the three subunits of ENaC were markedly induced in the distal colon by acute and chronic increases in aldosterone levels. Results indicate differential regulation of sgk and ENaC subunits by aldosterone in the distal colon. Distribution of sgk1 in the intestine beyond the aldosterone-responsive segments suggests that sgk1 may additionally regulate other sodium transporters in the intestinal epithelium.

Phosphorus kinetics in calves experimentally infected with Cooperia punctata evaluated by isotopic dilution

2005 ◽  
Vol 2005 ◽  
pp. 213-213
Author(s):  
R. R. Rodrigues ◽  
D. M. S. S. Vitti ◽  
S. M. Gennari ◽  
J.L. Guerra ◽  
A. L. Abdalla
Keyword(s):  
Small Intestine ◽  
Intestinal Epithelium ◽  
Present Experiment ◽  
Intestinal Parasite ◽  
Isotopic Dilution ◽  
Dilution Technique ◽  
Dietary Phosphorus ◽  
P Absorption

Cooperia punctata is the most prevalent intestinal parasite in young bovines in Brazil (Lima, 1998). The site of fixation of C. punctata is the upper part of the small intestine (Bailey, 1949), also the site of dietary phosphorus (P) absorption (Schröder et al, 1995), and the damage caused in the intestinal epithelium could interfere with P metabolism (Bown et al, 1989). The aim of the present experiment was to evaluate the P kinetics by using 32P isotopic dilution technique in calves submitted to single and trickle infection by C. punctata.

scholarly journals Oral Administration System Based on Meloxicam Nanocrystals: Decreased Dose Due to High Bioavailability Attenuates Risk of Gastrointestinal Side Effects

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 313 ◽  
Author(s):  
Noriaki Nagai ◽  
Fumihiko Ogata ◽  
Hiroko Otake ◽  
Naohito Kawasaki
Keyword(s):  
Therapeutic Effect ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Time Curve ◽  
Oral Formulations ◽  
Gastrointestinal Lesions ◽  
Bead Mill ◽  
Gastrointestinal Side Effects ◽  
High Bioavailability ◽  
High Absorption

Meloxicam (MLX) is widely applied as a therapy for rheumatoid arthritis (RA); however, it takes far too long to reach its peak plasma concentration for a quick onset effect, and gastrointestinal toxicity has been observed in RA patients taking it. To solve these problems, we designed MLX solid nanoparticles (MLX-NPs) by the bead mill method and used them to prepare new oral formulations. The particle size of the MLX-NPs was approximately 20-180 nm, and they remained in the nano-size range for 1 month. The tmax of MLX-NPs was shorter than that of traditional MLX dispersions (MLX-TDs), and the intestinal penetration of MLX-NPs was significantly higher in comparison with MLX-TDs (P < 0.05). Caveolae-dependent endocytosis (CavME), clathrin-dependent endocytosis (CME), and micropinocytosis (MP) were found to be related to the high intestinal penetration of MLX-NPs. The area under the plasma MLX concentration-time curve (AUC) for MLX-NPs was 5-fold higher than that for MLX-TDs (P < 0.05), and the AUC in rats administered 0.05 mg/kg MLX-NPs were similar to rats administered the therapeutic dose of 0.2 mg/kg MLX-TDs. In addition, the anti-inflammatory effect of the MLX-NPs was also significantly higher than that of MLX-TDs at the corresponding dose (P < 0.05), and the therapeutic effect of 0.2 mg/kg MLX-TDs and 0.05 mg/kg MLX-NPs in adjuvant-induced arthritis (AA) rats showed no difference. Furthermore, the gastrointestinal lesions in AA rats treated repetitively with 0.05 mg/kg MLX-NPs were fewer than in rats receiving 0.2 mg/kg MLX-TDs (P < 0.05). In conclusion, we demonstrate that MLX solid nanoparticles allow a quick onset of therapeutic effect and that three endocytosis pathways, CavME, CME, and MP, are related to the high absorption of solid nanoparticles. In addition, we found that MLX solid nanoparticles make it possible to reduce the amount of orally administered drugs, and treatment with low doses of MLX-NPs allows RA therapy without intestinal ulcerogenic responses to MLX. These findings are useful for designing therapies for RA patients.

GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats

2009 ◽  
Vol 297 (4) ◽  
pp. G663-G671 ◽  
Author(s):  
Tohru Hira ◽  
Taisuke Mochida ◽  
Kyoko Miyashita ◽  
Hiroshi Hara
Keyword(s):  
Small Intestine ◽  
Sampling Method ◽  
Rat Intestine ◽  
Mesenteric Vein ◽  
L Cells ◽  
Corn Protein ◽  
Before And After ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dose Dependent

Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small intestine. The duodenal, jejunal, and ileal administration of ZeinH induced dose-dependent increases in portal GLP-1 concentration. GLP-1 secretion in response to the ileal administration of ZeinH was higher than that in the duodenal or jejunal administration. Capsaicin treatment on esophageal vagal trunks abolished the GLP-1 secretion induced by duodenal ZeinH but did not affect the secretion induced by jejunal or ileal ZeinH. These results suggest that ZeinH in the jejunum or ileum directly stimulates GLP-1 secretion but duodenal ZeinH indirectly stimulates GLP-1 secretion via the vagal afferent nerve. A direct blood sampling method from the duodenal vein and ileal mesenteric vein revealed that ZeinH administered into the ligated duodenal loop enhanced GLP-1 concentration in the ileal mesenteric vein but not in the duodenal vein. This confirmed that ZeinH in the duodenum induces GLP-1 secretion from L cells located in the ileum by an indirect mechanism. These results indicate that a potent GLP-1-releasing peptide, ZeinH, induces GLP-1 secretion by direct and indirect mechanisms in the rat intestine.

scholarly journals Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Reiko Nakao ◽  
Weilin Shen ◽  
Yasuka Shimajiri ◽  
Kumiko Kainou ◽  
Yuki Sato ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Atrophy ◽  
Ubiquitin Ligase ◽  
Oral Intake ◽  
Rat Plasma ◽  
Cytochalasin D ◽  
Apical Side ◽  
Basolateral Side

AbstractWe previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy.

Changes in the distribution of Hymenolepis diminuta (Cestoda: Cyclophyllidea) within the rat intestine during prepatent development

1970 ◽  
Vol 48 (4) ◽  
pp. 761-769 ◽  
Author(s):  
Christine E. Cannon ◽  
D. F. Mettrick
Keyword(s):  
Small Intestine ◽  
Weight Distribution ◽  
Attachment Site ◽  
Pyloric Sphincter ◽  
Hymenolepis Diminuta ◽  
Rat Intestine ◽  
Intestinal Length ◽  
Attachment Sites ◽  
The Mean

The changes in the distribution of Hymenolepis diminuta within the rat intestine have been followed over the period 3 to 16 days postinfection using rats, each infected with 10 cysticercoids of H. diminuta, fed ad libitum on Purina Rat Chow.The parameters investigated were distribution of scolex attachment sites in the intestine, and distribution of parasite biomass in the intestine based on strobila length, ex vivo weight distribution, and in vivo weight distribution. Both the scoleces and biomass of 3- and 5-day-old worms are concentrated in the second quarter of the intestine. The mean scolex attachment point for 5-day-old worms was 39% of the total intestinal length behind the pyloric sphincter. Between days 5 and 7 there was a marked anterior migration of the young worms, so that at 7 days the mean scolex attachment site was 15% of the total intestinal length behind the stomach. Over the same period of time the mean in vivo weight distribution moved forward from a point 44% behind the pyloric sphincter to one only 23% along the intestine. After 7 days there was a gradual posteriad spreading of the scolex attachment sites and of the parasite biomass. Hymenolepis diminuta can attach itself anywhere in the anterior 75% of the intestine, including in front of the opening of the bile duct: no worms were found in the small intestine extending back into the caecum.The pattern of migration and the changes in worm distribution in the intestine suggest that H. diminuta selects an appropriate, but changing position, on one or more of the gradients that have been demonstrated or postulated along the length of the small intestine.It is also suggested that the long-term migration during prepatent development is interrelated, but distinct from the daily migrational movements that H. diminuta undergoes within the small intestine.

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