Stress effects on gastrointestinal transit in the rat.

Enck, Paul; Merlin, V; Erckenbrecht, J. F.; Wienbeck, M

doi:10.1136/gut.30.4.455

Cited by 112 publications

(79 citation statements)

References 19 publications

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“…The mean CTT obtained in one human study with and without the use of barium paste were 74.9±49.3 and 85.7±46.1 h, respectively (30). In a study by Enck et al (31), a mean CTT value of 15.5 h was obtained in rats. In that study, a carmine red solution was infused into the cecum of the rats and the time for the first discharge of a redcolored fecal pellet was considered as CTT.…”

Section: Cecal Arrival and Colonic Transit Times Of The Amb Slnsmentioning

confidence: 98%

“…The difference in the values obtained in the present study and that from the study by Enck et al (31) is due to the methods employed by both groups. The CTT estimation by Enck et al (31) was based on infusing of the marker solution directly into the cecum, which has the potential of staining the fecal matter already present before the study commenced.…”

Section: Cecal Arrival and Colonic Transit Times Of The Amb Slnsmentioning

confidence: 99%

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Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

et al. 2015

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Abstract. Amphotericin B (AmB) is poorly absorbed from the gastrointestinal tract. Recent studies have suggested enhanced drug absorption from solid lipid nanoparticles (SLN). Little is known of the fate of AmB absorption within the gastrointestinal tract, and no gastrointestinal transit study has yet been performed on AmB-containing nano-formulations. We aimed to investigate the effect of food on the gastrointestinal transit properties of an AmB-containing SLN in rats. Three SLNs containing AmB, paracetamol, or sulfasalazine were formulated using cocoa butter and beeswax as lipid matrices and simultaneously administered orally to Sprague-Dawley rats. Paracetamol and sulfapyridine were used as marker drugs for estimating gastric emptying and cecal arrival, respectively. The pharmacokinetic data generated for paracetamol and sulfapyridine were used in estimating the absorption of the AmB SLNs in the small and large intestines, respectively. A delayed rate of AmB absorption was observed in the fed state; however, the extent of absorption was not affected by food. Specifically, the percentages of AmB absorption during the fasted state in the stomach, small intestine, and colon were not significantly different from absorption within the respective regions in the fed state. In both states, however, absorption was highest in the colon and appeared to be a combination of absorption from the small intestine plus absorption proper within the colon. The study suggests that AmB SLN, irrespective of food status, is slowly but predominantly taken up by the lymph, making the small intestine the most favorable site for the delivery of the AmB SLNs.

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Section: Cecal Arrival and Colonic Transit Times Of The Amb Slnsmentioning

confidence: 98%

Section: Cecal Arrival and Colonic Transit Times Of The Amb Slnsmentioning

confidence: 99%

Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

et al. 2015

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“…1). Absorption of nitrite was represented as occurring from the stomach (k abs ) because the plasma nitrite concentration reaches its highest value within 25 min following gavage, and the time to empty a rat's stomach is about 2 h (Encke et al, 1989). If absorption of nitrite from the stomach is a saturable process (see below), the uptake rate at concentrations below the apparent K m (in which linear kinetics are adequate) is approximated by…”

Section: Figmentioning

confidence: 99%

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

Kohn

Melnick²,

Ye³

et al. 2002

Drug Metab Dispos

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ABSTRACT:A biologically based mathematical model was created to characterize time and dose-dependent relationships between exposure to nitrite and induction of methemoglobinemia. The model includes mass action equations for processes known to occur: oral absorption of nitrite, elimination from the plasma, partitioning between plasma and erythrocytes, binding of nitrite to hemoglobin and methemoglobin, and the free radical chain reaction for hemoglobin oxidation. The model also includes Michaelis-Menten kinetics for methemoglobin reductase-catalyzed regeneration of hemoglobin. Body weight-scaled rate constants for absorption (k a ) and elimination (k e ), the effective erythrocyte/plasma partition coefficient (P), and the apparent K m for methemoglobin reductase were the only parameters estimated by formal optimization to reproduce the observed time course data. Time courses of plasma nitrite concentrations and blood levels of hemoglobin and methemoglobin in male and female rats that had received single intravenous or oral doses of sodium nitrite were measured. Peak plasma levels of nitrite were achieved in both sexes approximately 30 min after oral exposure, and peak methemoglobin levels were achieved after 100 min. The model predicts that 10% of the hemoglobin is oxidized to the ferric form after oral doses of 15.9 mg/kg in male rats and 11.0 mg/kg in female rats and after intravenous doses of 8.9 and 7.1 mg/kg in male and female rats, respectively. The t 1/2 for recovery from methemoglobinemia was 60 to 120 min depending on dose and route of administration. A sensitivity analysis of the model was performed to identify to which parameters the predictions of the model were most sensitive and guide attempts to simplify the model. Replacement of the V max of methemoglobin reductase with a value representative of humans predicted a 10% methemoglobinemia following an intravenous dose of 5.8 mg/kg, in close agreement with an observed value of 5.7 mg/kg for humans.

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“…The stimulation of intestinal contraction and colonic transit are the most consistent patterns in the motility response of the intestinal tract to acute stress (2,3); however, the stress-gut interactions are enormously complex (1). Both stress-induced anxiety and intestinal disorders are traced, from among other molecular pathologies, to the inappropriate responses of the central and͞or peripheral serotonin (5-HT) system (4,5).…”

mentioning

confidence: 99%

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Smriga

Torii

2003

Proc. Natl. Acad. Sci. U.S.A.

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S tress and stress-induced anxiety play a major role in functional intestinal disorders (1). The stimulation of intestinal contraction and colonic transit are the most consistent patterns in the motility response of the intestinal tract to acute stress (2, 3); however, the stress-gut interactions are enormously complex (1). Both stress-induced anxiety and intestinal disorders are traced, from among other molecular pathologies, to the inappropriate responses of the central and͞or peripheral serotonin (5-HT) system (4, 5). Among the 5-HT receptors, the 5-HT 4 receptor plays a ''prostress'' role in the gut and throughout the body by mobilizing energy and facilitating behavioral, gastrointestinal, and cardiovascular stress responses (6, 7).5-HT 4 receptors are located within the cells and neurons of the gastrointestinal tract (6,8). Agonists on the 5-HT 4 receptor increase cholinergic transmission (9) and thus contract the smooth muscle in the rat and guinea pig ileum † and the human colon (11). Antagonists on the 5-HT 4 receptor do not affect normal, healthy gut function (12) but prevent the disturbances caused by stress (4) or high 5-HT activity (13). Thus, 5-HT 4 receptor antagonists are promising targets for the treatment of diarrhea-predominant irritable bowel syndrome (12). In addition to their effect on the gastrointestinal tract, 5-HT 4 antagonists block corticosteroid secretion in the adrenal cortex (14), 5-HTinduced tachycardia (15, 16), and stress-induced anxiety (17).However, the 5-HT receptor system is heterogeneous (18), and direct receptor targeting often causes side effects, such as diarrhea, gastric bleeding, and anxiety (19). Therefore, it is not surprising that few satisfying pharmacological treatments of stress-triggered, 5-HT-mediated intestinal disorders exist and that other therapeutic approaches, namely nutritional ones, are sought (20)(21)(22)). An interesting candidate to include in ''nutritional management'' of stress-related gastrointestinal disorders would be an essential amino acid, L-lysine (Lys). Lys blunted stress-induced anxiety in rats (23), whereas a dietary deficiency of Lys increased stress-induced colonic transit and anxiety, because of an enhanced transmission of 5-HT in the amygdala (24).Because the effects of Lys overlap with the ''antistress'' effects of the 5-HT 4 receptor antagonists (4), we hypothesized that dietary Lys could act as a partial antagonist on the 5-HT 4 receptors. The present study examined whether the provision of oral L-lysine might result in the blockage of 5-HT-mediated pathologies linked to stress exposure and͞or 5-HT sensitization in rats. Ileum contractions, stress-induced fecal excretion, diarrhea, anxiety, and tachycardia were monitored. The fractions obtained were washed once by centrifugation with 10-fold volume of the buffer, and the microsomal fraction was stored as receptor at Ϫ80°C until use. To determine the binding degree, the inhibition rate of Lys and a positive reference substance were calculated from binding of a tracer to a receptor. D...

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Stress effects on gastrointestinal transit in the rat.

Cited by 112 publications

References 19 publications

Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

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