COMPARISON OF THE METABOLISM OF TESTOSTERONE UNDECANOATE AND TESTOSTERONE IN THE GASTROINTESTINAL WALL OF THE RAT IN VITRO AND IN VIVO

1977 ◽  
Vol 86 (1) ◽  
pp. 216-224 ◽  
Author(s):  
J. Geelen ◽  
A. Coert ◽  
R. Meijer ◽  
J. van der Vies
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Portal Vein ◽  
Oral Administration ◽  
Small Extent ◽  
Great Similarity ◽  
Testosterone Undecanoate ◽  
Different Parts

ABSTRACT The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.

Ileal and hindgut fermentation in the growing pig fed a human-type diet

2020 ◽  
Vol 124 (6) ◽  
pp. 567-576 ◽  
Author(s):  
Anna M. E. Hoogeveen ◽  
Paul J. Moughan ◽  
Edward S. de Haas ◽  
Paul Blatchford ◽  
Warren C. McNabb ◽  
...  
Keyword(s):  
Body Weight ◽  
Organic Matter ◽  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Taxonomic Composition ◽  
Human Type ◽  
Growing Pig ◽  
Microbial Inocula

AbstractDietary fibre fermentation in humans and monogastric animals is considered to occur in the hindgut, but it may also occur in the lower small intestine. This study aimed to compare ileal and hindgut fermentation in the growing pig fed a human-type diet using a combined in vivo/in vitro methodology. Five pigs (23 (sd 1·6) kg body weight) were fed a human-type diet. On day 15, pigs were euthanised. Digesta from terminal jejunum and terminal ileum were collected as substrates for fermentation. Ileal and caecal digesta were collected for preparing microbial inocula. Terminal jejunal digesta were fermented in vitro with a pooled ileal digesta inoculum for 2 h, whereas terminal ileal digesta were fermented in vitro with a pooled caecal digesta inoculum for 24 h. The ileal organic matter fermentability (28 %) was not different from hindgut fermentation (35 %). However, the organic matter fermented was 66 % greater for ileal fermentation than hindgut fermentation (P = 0·04). Total numbers of bacteria in ileal and caecal digesta did not differ (P = 0·09). Differences (P < 0·05) were observed in the taxonomic composition. For instance, ileal digesta contained 32-fold greater number of the genus Enterococcus, whereas caecal digesta had a 227-fold greater number of the genus Ruminococcus. Acetate synthesis and iso-valerate synthesis were greater (P < 0·05) for ileal fermentation than hindgut fermentation, but propionate, butyrate and valerate synthesis was lower. SCFA were absorbed in the gastrointestinal tract location where they were synthesised. In conclusion, a quantitatively important degree of fermentation occurs in the ileum of the growing pig fed a human-type diet.

scholarly journals Application of selective extraction to the study of iron species present in diet and rat gastrointestinal tract contents

1992 ◽  
Vol 67 (3) ◽  
pp. 437-444 ◽  
Author(s):  
Robert J. Simpson ◽  
Sanjiv Sidhar ◽  
Timothy J. Peters
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Stomach Contents ◽  
Selective Extraction ◽  
Proximal Small Intestine ◽  
Exchangeable Fraction ◽  
Fe Speciation ◽  
Pelleted Diet

Iron speciation in rodent diet and rat gastrointestinal tract lumen during dietary digestion and absorption was investigated with a novel selective extraction technique. Five Fe fractions were identified, namely exchangeable (soluble in 1 M-magnesium chloride), carbonate-bound (soluble in mild acid), oxide-bound (soluble in hydroxylamine–acetic acid), organic-bound (soluble after treatment with peroxide in nitric acid) and residual. Fe from the pelleted diet was mobilized by rat stomach to the exchangeable fraction, then redistributed to the carbonate- and oxide-bound fractions on passage through the proximal small intestine. In vitro incubation of diet with hydrochloric acid failed to mimic the in vivo effect of the stomach. In vitro neutralization of stomach contents with bicarbonate was found to produce a similar effect on Fe speciation to that seen when diet passed the proximal small intestine in vivo. Comparison of59Fe speciation in extrinsically labelled diet with endogenous Fe speciation showed that extrinsic labelling does not uniformly label all endogenous species. The experiments suggest that selective extraction may provide a useful approach to the study of Fe species present in diets, in vitro digestions and gastrointestinal contents.

scholarly journals Comparing the Ileal and Hindgut Fermentations in the Pig Model (P08-087-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carlos Montoya ◽  
Edward de Haas ◽  
Paul Blatchford ◽  
Paul Moughan
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Tertiary Education ◽  
Short Chain Fatty Acids ◽  
Pig Model ◽  
Funding Sources ◽  
Important Amount ◽  
Caecal Fermentation

Abstract Objectives This study aimed to compare ileal and hindgut fermentations in the pig model using a combined in vivo/in vitro methodology. Methods Pigs (23 kg bodyweight, n = 5) were fed a human-type diet for 15 days. On day 15, pigs were euthanased and the small intestine was immediately dissected out and ligated in three equal lengths. Digesta from the last 50 cm of the second (terminal jejunum) and last (terminal ileum) third sections of the small intestine were collected as substrates. Digesta from the remaining last third (i.e., last third minus 50 cm) of the small intestine (ileum) was collected along with caecal digesta for preparing inocula. Terminal jejunal digesta substrates were fermented in vitro with a pooled ileal digesta inoculum for 2 h (ileal fermentation), while terminal ileal digesta substrates were fermented in vitro with a pooled caecal digesta inoculum for 24 h (hindgut fermentation). Results The ileal organic matter (OM) fermentability (28%) was similar than the hindgut counterpart (35%) (P > 0.05). However, the fermentable OM was 63% higher during ileal fermentation than hindgut fermentation (P < 0.05). The production of acetic, isovaleric and succinic acids was higher during ileal fermentation than caecal fermentation (P < 0.05), but the production of propionic, iso-butyric, butyric, valeric and pyruvic acids was lower (P < 0.05). The SCFAs produced in each gastrointestinal tract location was absorbed in their respective gastrointestinal tract location. Conclusions An important amount of OM is fermented in the ileum producing comparable amounts of short-chain fatty acids and organic acids to hindgut fermentation. This challenge the current paradigm concerning gastrointestinal tract fermentation. Funding Sources Centre of Research Excellence Fund from the Tertiary Education.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma
Keyword(s):  
Human Consumption ◽  
In Vivo Models ◽  
Sugar Amino Acids ◽  
Opuntia Species ◽  
Therapeutic Uses ◽  
Anti Inflammatory ◽  
Online Library ◽  
Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

scholarly journals Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moe Ichikawa ◽  
Hiroki Akamine ◽  
Michika Murata ◽  
Sumito Ito ◽  
Kazuo Takayama ◽  
...  
Keyword(s):  
Small Intestine ◽  
Drug Absorption ◽  
Cell Model ◽  
Negative Effects ◽  
Piggybac Transposon ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cyp3a4 Expression

AbstractCaco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.

Ellagitannins, Gallotannins and their Metabolites- The Contribution to the Anti-Inflammatory Effect of Food Products and Medicinal Plants

2019 ◽  
Vol 25 (37) ◽  
pp. 4946-4967 ◽  
Author(s):  
Anna K. Kiss ◽  
Jakub P. Piwowarski
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Health Effects ◽  
Biological Effects ◽  
Food Products ◽  
Anti Inflammatory ◽  
The Impact

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.

scholarly journals Absorption of lactulose from mammalian gastrointestinal tract

1979 ◽  
Vol 41 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. F. Evered ◽  
F. Sadoogh-Abasian
Keyword(s):  
Small Intestine ◽  
Calcium Ions ◽  
Clinical Evidence ◽  
Buccal Cavity ◽  
Rat Small Intestine ◽  
Sodium Ions ◽  
Mode Of Transport ◽  
Poor Absorption

1. The disaccharide lactulose (galactosyl-β-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo.2. These results confirm indirect clinical evidence of poor absorption from the intestine.3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from the buccal cavity.4. The presence of ouabain, or absence of Na+, did not decrease the absorption of lactulose from small intestine.5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.

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