Studies on the Effect of Dose Size on the Absorption of beta-Carotene by the Rat in vivo

1999 ◽  
Vol 69 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Chen ◽  
Oace ◽  
Wolf

This study was carried out to choose between two hypotheses with respect to the regulation of beta-carotene (BC) conversion to retinol in the whole animal: uptake of BC into intestinal mucosa is limited by saturation of an intestinal receptor; or the conversion to retinol is limited by saturation of the conversion enzyme(s). Groups of rats were given five different dose levels of labeled BC by stomach tube. Labeled and total BC and retinol were isolated from tissues and intestinal contents after 4 h. Results showed a positive linear relationship between BC in the intestinal wall and the dose administered, with no saturation level up to 1440 mug administered. Per cent formation of newly formed retinol from newly absorbed (i.e., labeled) BC was 20–26% of the three lower dose groups, 10% for the highest dose. No retinyl esters could be detected in the intestine. Most of the administered BC was in the intestinal contents, about 100-times more than in the intestinal wall and mucosa. Newly formed retinol in plasma was about 10-times that in liver. Small amounts of newly absorbed BC were found in liver, but no labeled retinyl esters. These results suggest that the absorption of BC is very inefficient; that it does not occur through an intestinal receptor; that the formation of retinol is regulated at the level of the conversion enzyme(s).

2004 ◽  
Vol 13 (9) ◽  
pp. 558-561 ◽  
Author(s):  
Christophe Antille ◽  
Christian Tran ◽  
Olivier Sorg ◽  
Jean-Hilaire Saurat

1992 ◽  
Vol 263 (4) ◽  
pp. G480-G486 ◽  
Author(s):  
X. D. Wang ◽  
N. I. Krinsky ◽  
R. P. Marini ◽  
G. Tang ◽  
J. Yu ◽  
...  

To determine the appropriateness of the ferret as a model for human beta-carotene (beta-C) metabolism, we have perfused both 15,15'-beta-[14C]C and unlabeled beta-C through the upper 30-cm portion of the small intestine of ferrets in vivo. The effluents of a mesenteric lymph duct cannulation and a common bile duct cannulation, as well as portal vein blood periodically sampled via an indwelling catheter, were collected. Ten percent (9.5 +/- 0.06%) of the total administered beta-C was taken up by the intestine after a 4-h perfusion. Of the radioactivity taken up, 68.6 +/- 6.5% remained in the intestinal mucosa, 3.2 +/- 0.2% was recovered in the lymph, and 28.2 +/- 6.5% (calculated) was absorbed via the portal system. The total uptake/absorption of beta-C was 12.9 +/- 6.8 nmol.h-1.30 cm intestine-1. Large amounts of unchanged beta-C and relatively small amounts of both beta-apo-12'-carotenal and beta-apo-10'-carotenal were isolated in the intestinal mucosa after a 4-h perfusion with beta-C. Considerable amounts of metabolites more polar than retinol were formed and comprised 35% of the total radioactivity recovered in the intestinal mucosa. Polar metabolites were absorbed mostly into the portal venous system, whereas retinol and retinyl esters were absorbed mainly into the mesenteric lymph. Of the total absorbed radioactivity in lymph, 10 +/- 1.0% appeared as unchanged beta-C, with peak absorption occurring at 3 h after beginning the perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


1973 ◽  
Vol 45 (2) ◽  
pp. 199-212 ◽  
Author(s):  
A. M. Asatoor ◽  
Amrit Chadha ◽  
M. D. Milne ◽  
D. I. Prosser

1. Studies have been made of jejunal absorption rates in vivo in the rat of the stereoisomers of alanylphenylalanine, leucyl-leucine and glycyltryptophan. Absorption rates of l-alanyl-l-phenylalanine were about 200 times those of d-alanyl-d-phenylalanine, l-leucyl-l-leucine about 24 times those of the dd-isomer, and glycyl-l-tryptophan 5 times those of glycyl-d-tryptophan. The mixed ld- and ld-isomers were absorbed at intermediate rates. 2. Absorption rates were positively correlated with the rate of hydrolysis of each dipeptide by homogenates of rat intestinal mucosa. The transport rate and rate of hydrolysis of glycyl-d-tryptophan, d-alanyl-d-phenylalanine and d-leucyl-d-leucine were significantly greater in the ileum than in the jejunum. 3. When given by stomach tube the most slowly absorbed dipeptides, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan were the only ones to be excreted in significant amounts in the urine, showing that they were absorbed as the entire molecule and were resistant to hydrolysis by tissue peptidases. 4. There was a close inverse correlation between the rates of transport by rat jejunum of glycine, d-alanine, d-leucine, d-phenylalanine, d-tryptophan, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan and the molecular weight of each compound, suggesting that diffusion mechanisms play an appreciable part in jejunal absorption of these compounds. No such correlation was found in the case of the ileum.


Author(s):  
R. B. Moyes ◽  
R. E. Droleskey ◽  
M. H. Kogut ◽  
J. R. DeLoach

Salmonella enteritidis (SE) is of great concern to the poultry industry due to the organism's ability to penetrate the intestinal mucosa of the laying hen and subsequently colonize the ovaries and yolk membrane. The resultant subclinical infection can lead to SE infection of raw eggs and egg products. Interference with the ability of the organism to invade has been linked to the activation and recruitment of inflammatory polymorphonuclear cells, heterophils, to the lamina propria of the intestinal tract.Recently it has been established that heterophil activation and increased resistance to SE organ invasion can be accomplished by the administration of SE-immune lymphokines (SE-ILK) obtained from supernatants of concanavalin-A stimulated SE immune T lymphocytes from SE hyperimmunized hens. Invasion of SE into the lamina propria provides a secondary signal for directing activated heterophils to the site of SE invasion.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 66
Author(s):  
Rashmita Pradhan ◽  
Phuong A. Ngo ◽  
Luz d. C. Martínez-Sánchez ◽  
Markus F. Neurath ◽  
Rocío López-Posadas

Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.


2006 ◽  
Vol 72 (2) ◽  
pp. 1507-1514 ◽  
Author(s):  
Mark J. Daniels ◽  
Malcolm R. Wood ◽  
Mark Yeager

ABSTRACT The water channel protein PvTIP3;1 (α-TIP) is a member of the major intrinsic protein (MIP) membrane channel family. We overexpressed this eukaryotic aquaporin in the methylotrophic yeast Pichia pastoris, and immunogold labeling of cellular cryosections showed that the protein accumulated in the plasma membrane, as well as vacuolar and other intracellular membranes. We then developed an in vivo functional assay for water channel activity that measures the change in optical absorbance of spheroplasts following an osmotic shock. Spheroplasts of wild-type P. pastoris displayed a linear relationship between absorbance and osmotic shock level. However, spheroplasts of P. pastoris expressing PvTIP3;1 showed a break in this linear relationship corresponding to hypo-osmotically induced lysis. It is the difference between control and transformed spheroplasts under conditions of hypo-osmotic shock that forms the basis of our aquaporin activity assay. The aquaporin inhibitor mercury chloride blocked water channel activity but had no effect on wild-type yeast. Osmotically shocked yeast cells were affected only slightly by expression of the Escherichia coli glycerol channel GlpF, which belongs to the MIP family but is a weak water channel. The important role that aquaporins play in human physiology has led to a growing interest in their potential as drug targets for treatment of hypertension and congestive heart failure, as well as other fluid overload states. The simplicity of this assay that is specific for water channel activity should enable rapid screening for compounds that modulate water channel activity.


2021 ◽  
pp. 65-70
Author(s):  
Susruta Sen ◽  
Indranil Chakraborty ◽  
Mousumi Bandyopadhyay ◽  
Indrani Pathak ◽  
Sharmistha Choudhuri

Introduction: Senile cataract is the commonest worldwide cause of treatable blindness, most often due to excess reactive oxygen species [ROS]. Anti-oxidant vitamins namely beta-carotene, ascorbate and tocopherol and enzymes like superoxide dismutase (SOD), constitute rst line defenses against ROS assault, while malondialdehyde (MDA) levels indicate the total burden of lipid peroxidation in-vivo. Objectives: We aimed to compare the levels of above ve analytes in senile cataract patients in contrast to apparently healthy controls and also among smoking and non-smoking sub groups of both cases and controls. Methods: A hospital-based case-control study, was conducted with 102 cases of senile cataract and 102 control subjects, following strict inclusion and exclusion criteria. Recruited individuals were sub-categorized into smokers and non-smokers. After overnight fasting (12 hours), 10 ml blood was drawn aseptically. Serum and plasma were separated and used for biochemical estimations of all ve analytes, following established protocols. Levels were compared between cases and controls as well as between the smoking and non-smoking sub-sections of both groups. Results: Signicantly lower levels of plasma ascorbate and serum tocopherol were seen in cases as compared to controls (P=0.0078 and P<0.0001 respectively). Signicantly lower levels of serum beta carotene (P<0.0001), tocopherol (P<0.0001), plasma ascorbate (P<0.0001), and SOD (P<0.0001). Signicantly higher level of serum MDA (P= 0.0494) was seen in the smokers, as compared to non-smokers Conclusions: Lowered serum tocopherol and plasma ascorbate were signicant factors leading to senile cataract. Furthermore, smoking was found crucial in loss of anti-oxidant defenses and subsequent development of cataract.


1976 ◽  
Vol 231 (1) ◽  
pp. 258-264 ◽  
Author(s):  
BJ Buchanan ◽  
JP Filkins

Endotoxin clearances in vivo and by the isolated perfused rat liver were evaluated via bioassay in lead-sensitized rats. A linear relationship between the probit of shock lethality and the endotoxin dose in the probit range of 4-6 was validated. Endotoxin clearance in normal, fed rats displayed a linear relationship between the logarithm of the blood endotoxin concentration and time throughout the period of 15-240 min at doses of 500 and 1,000 mug/ rat; the half-time values were 58-63 min. Decreasing the endotoxin dose to 250 mug resulted in multiphasic clearance curves. Induction of tolerance to endotoxin resulted in marked acceleration of endotoxin clearance. Endotoxin clearance from the isolated perfused rat liver was not influenced by serum or rat blood as compared to clearance from a balanced salt solution. These data suggest that a physiologically stressful dose of endotoxin is slowly cleared from the blood and, therefore, circulates for prolonged periods.


Drug Research ◽  
2018 ◽  
Vol 69 (03) ◽  
pp. 173-180 ◽  
Author(s):  
Bilal Houshaymi ◽  
Nadine Nasreddine ◽  
Mamdouh Kedees ◽  
Zeina Soayfane

AbstractThe bioavailability of ivermectin is modulated by lipid-based formulations and membrane efflux transporters such as Breast Cancer Resistance Protein and P-glycoprotein (BCRP and P-gp). We have investigated the effect of oleic acid on the uptake of ivermectin in vitro using Caco-2 cells and in vivo in the intestines of wild-type mice. Complex micelles (M) with oleic acid induced a significant increase (e. g. for M3 was 7-fold, p≤0.001) in the uptake of the drug in a time-dependent manner with no involvement of cholesterol in the mechanism. In vivo results showed a significant increase in the concentration of plasma and intestinal mucosa ivermectin (p≤0.01) in mice receiving oleic acid-based drug formulation. We also examined the expression of the drug efflux transporter, BCRP and P-gp in Caco-2 cells and found a significant decrease (p≤0.001) in their level in the presence of 5 mM oleic acid. Treatment of mice with oleic acid-based formulation showed a significant decrease in the activity of P-gp in the intestinal mucosa (p≤0.01). This study highlighted the effect of oleic acid in decreasing the expression and the activity of P-gp-mediated ivermectin efflux and in limiting the drug absorption by increasing its uptake and bioavailability in Caco-2 cells and intestine, respectively.


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