Exercise hyperthermia induces greater changes in gastrointestinal permeability than equivalent passive hyperthermia

A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, an asymptomatic lupus model (increased anti-dsDNA without lupus nephritis), and age-matched wild-type (WT) mice. Severity of indomethacin-induced enteropathy in FcgRIIb-/- mice was higher than WT mice as demonstrated by survival analysis, intestinal injury (histology, immune-deposition, and intestinal cytokines), gut leakage (FITC-dextran assay and endotoxemia), serum cytokines, and lupus characteristics (anti-dsDNA, renal injury, and proteinuria). Prominent responses of FcgRIIb-/- macrophages toward lipopolysaccharide (LPS) compared to WT cells due to the expression of only activating-FcgRs without inhibitory-FcgRIIb were demonstrated. Extracellular flux analysis indicated the greater mitochondria activity (increased respiratory capacity and respiratory reserve) in FcgRIIb-/- macrophages with a concordant decrease in glycolysis activity when compared to WT cells. In conclusion, gut leakage-induced endotoxemia is more severe in indomethacin-administered FcgRIIb-/- mice than WT, possibly due to the enhanced indomethacin toxicity from lupus-induced intestinal immune-deposition. Due to a lack of inhibitory-FcgRIIb expression, mitochondrial function, and cytokine production of FcgRIIb-/- macrophages were more prominent than WT cells. Hence, lupus disease-activation from NSAIDs-enteropathy-induced gut leakage is possible.

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PSX-B-10 Effect of undigested neutral detergent fiber concentration and forage inclusion rate on ruminal pH, reticular motility, and total tract permeability for finishing beef heifers

Journal of Animal Science ◽

10.1093/jas/skab235.811 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 457-458

Author(s):

Murillo C Pereira ◽

Karen A Beauchemin ◽

Tim A McAllister ◽

Wenzhu Yang ◽

Joyce Van Donkersgoed ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Dry Matter ◽

Latin Square ◽

Barley Grain ◽

Neutral Detergent Fiber ◽

Fiber Concentration ◽

Eating Time ◽

Ruminal Ph ◽

Contraction Duration ◽

Gastrointestinal Permeability

Abstract This study evaluated the effects of undigested neutral detergent fiber (uNDF) concentration and forage inclusion (FI) rate on dry matter (DM) intake, ruminal pH, reticular contractions, and gastrointestinal permeability for finishing beef cattle. Five ruminally cannulated Hereford′Simmental heifers (699±69.1 kg) were used in an incomplete 6×6 Latin square (26-d periods) with a 2×3 factorial treatment arrangement. Barley grain-based diets were formulated using barley silage or wheat straw to provide low or high uNDF (7.1 vs. 8.5% DM) with forage proportions of 5, 10, or 15% of dietary DM. Dry matter intake (P ≥ 0.10) and eating time (P ≥ 0.13) were not affected by uNDF, FI, or uNDF′FI. With low uNDF diets, increasing FI numerically (P = 0.02) increased rumination time (min/d); while, with high uNDF diets, rumination time increased with 5 to 10% FI, but not thereafter (P = 0.03). Mean ruminal pH was not affected by uNDF (6.17 vs. 6.19; P = 0.08), but increased with increasing FI (6.04b, 6.23a, and 6.28a; P = 0.02). Duration of ruminal pH < 5.5 was not affected by uNDF but tended (P = 0.07) to be reduced with increasing FI. High uNDF diet tended to increase the frequency of reticular contractions (1.43 vs. 1.51 contractions/min; P = 0.07) but decreased the contraction duration (13.2 vs. 14.1 sec; P = 0.04). Increasing FI increased contraction frequency (1.39b, 1.50a, and 1.53a contractions/min; P = 0.03) and tended to reduce contraction duration as forage increased from 5 to 10 and 15% (14.3, 13.1, and 13.6 sec; P = 0.07). Feeding high uNDF decreased (P = 0.05) permeability of the gastrointestinal tract based on the appearance of Cr-EDTA in urine following an intra-ruminal dose. Increasing FI tended to reduce gastrointestinal tract permeability (P = 0.06). Limited interactions indicate that uNDF and FI act independently suggesting that increasing dietary uNDF, without increasing FI rate, can stimulate frequency of reticulo-ruminal contractions and reduce gastrointestinal permeability for finishing cattle.

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Development of alendronate niosomal delivery system for gastrointestinal permeability improvement

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102885 ◽

2021 ◽

pp. 102885

Author(s):

Koson Saeting ◽

Ampol Mitrevej ◽

Hans Leuenberger ◽

Nuttanan Sinchaipanid

Keyword(s):

Delivery System ◽

Gastrointestinal Permeability

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Application of Caco-2 Cell Line in Herb-Drug Interaction Studies: Current Approaches and Challenges

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j30k63 ◽

2014 ◽

Vol 17 (1) ◽

pp. 1 ◽

Cited By ~ 40

Author(s):

Charles Awortwe ◽

P.S. Fasinu ◽

B. Rosenkranz

Keyword(s):

Small Intestine ◽

Drug Interactions ◽

Cell Line ◽

Cytochrome P450 Enzymes ◽

Human Small Intestine ◽

Clinical Investigations ◽

New Chemical Entities ◽

Biopharmaceutics Classification ◽

Gastrointestinal Permeability ◽

Laboratory Protocol

The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Influence of passive hyperthermia and diurnal variation on exercise performance and cognitive function in the heat

Extreme Physiology & Medicine ◽

10.1186/2046-7648-4-s1-a155 ◽

2015 ◽

Vol 4 (S1) ◽

Cited By ~ 1

Author(s):

Hidenori Otani ◽

Mitsuharu Kaya ◽

Akira Tamaki ◽

Heita Goto ◽

Junzo Tsujita

Keyword(s):

Cognitive Function ◽

Diurnal Variation ◽

Exercise Performance ◽

Passive Hyperthermia

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High gastrointestinal permeability and local metabolism of naringenin: influence of antibiotic treatment on absorption and metabolism

British Journal Of Nutrition ◽

10.1017/s0007114515001671 ◽

2015 ◽

Vol 114 (2) ◽

pp. 169-180 ◽

Cited By ~ 25

Author(s):

Naiara Orrego-Lagarón ◽

Miriam Martínez-Huélamo ◽

Anna Vallverdú-Queralt ◽

Rosa M. Lamuela-Raventos ◽

Elvira Escribano-Ferrer

Keyword(s):

Small Intestine ◽

Gastrointestinal Tract ◽

Perfusion Model ◽

First Pass Metabolism ◽

First Pass ◽

Phase Ii Metabolites ◽

Local Metabolism ◽

Bile Samples ◽

Gastrointestinal Permeability ◽

Pass Metabolism

The present study aims to determine the permeability of naringenin in the stomach, small intestine and colon, to evaluate intestinal and hepatic first-pass metabolism, and to study the influence of the microbiota on the absorption and disposition of naringenin (3·5 μg/ml). A single-pass intestinal perfusion model in mice (n4–6) was used. Perfusate (every 10 min), blood (at 60 min) and bile samples were taken and analysed to evaluate the presence of naringenin and its metabolites by an HPLC-MS/MS method. To study the influence of the microbiota on the bioavailability of naringenin, a group of animals received the antibiotic rifaximin (50 mg/kg per d) for 5 d, and naringenin permeability was determined in the colon. Naringenin was absorbed well throughout the gastrointestinal tract but mainly in the small intestine and colon (mean permeability coefficient 7·80 (sd1·54) × 10− 4cm/s and 5·49 (sd1·86) × 10− 4cm/s, respectively), at a level similar to the highly permeable compound, naproxen (6·39 (sd1·23) × 10− 4cm/s). According to the high amounts of metabolites found in the perfusate compared to the bile and plasma, naringenin underwent extensive intestinal first-pass metabolism, and the main metabolites excreted were sulfates (84·00 (sd12·14)%), followed by glucuronides (8·40 (sd5·67)%). Phase II metabolites were found in all perfusates from 5 min of sampling. Mice treated with rifaximin showed a decrease in naringenin permeability and in the amounts of 4-hydroxyhippuric acid and hippuric acid in the lumen. Naringenin was well absorbed throughout the gastrointestinal tract and its poor bioavailability was due mainly to high intestinal metabolism.

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