Reduced Intestinal Permeability Measured by Differently Sized Polyethylene Glycols in Acute Uremic Rats

Magnusson, Martin; Magnusson, Karl‐Eric; Sundqvist, Tommy; Denneberg, Torsten

doi:10.1159/000186738

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…The absorption rate and the amount of ciprofloxacin absorbed via the gut have never been investigated for rats suffering from RF. However, Magnusson et al (13) evidenced that in rats, chronic RF induces changes in intestinal mucosa that lead to an increased intestinal permeability towards polar drugs via an increased water absorption. The increase in ciprofloxacin K a is Mean Ϯ SD (median) for pharmacokinetic parameter b : a In each group, the number of control rats was seven and the number of rats with RF was seven.…”

Section: Discussionmentioning

confidence: 99%

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Nouaille-Degorce

Veau

Dautrey

et al. 1998

Antimicrob Agents Chemother

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Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P< 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.

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Section: Discussionmentioning

confidence: 99%

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Nouaille-Degorce

Veau

Dautrey

et al. 1998

Antimicrob Agents Chemother

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“…Magnusson et al . reported that intestinal permeability was increased in chronic uremic rat while it was decreased in acute cases 150,151 . They also noted that a low protein diet decreased the hyperpermeability in chronic cases.…”

Section: Intestinal Barrier Dysfunction and Diseasesmentioning

confidence: 93%

Intestinal barrier: An interface between health and disease

Farhadi¹,

Banan²,

Fields³

et al. 2003

J of Gastro and Hepatol

459

310

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The intestine constitutes the largest interface between a person and his or her environment, and an intact intestinal barrier is thus essential in maintaining health and preventing tissue injury and several diseases. The intestinal barrier has various immunological and non-immunological components. The epithelial barrier is one of the most important non-immunological components. Hyperpermeability of this barrier is believed to contribute to the pathogenesis of several gastrointestinal disorders including inflammatory bowel disease, celiac disease and food allergy. Hence, assessing barrier integrity is of the utmost importance. One of the more quantitative gauges for this assessment is transepithelial permeability of various molecular probes, among which sugars are commonly used. Measures of intestinal permeability might also be useful as markers for assessment of prognosis and follow up in various gastrointestinal disorders. The present article is a review of the normal and abnormal functioning of the intestinal barrier, the diseases that can result from loss of barrier integrity, and some promising agents and strategies for restoring barrier normality and integrity.

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“…Neutrophil activation and dysfunction are probably caused by endotoxemia 14 , a well-recognized phenomenon in ESRD. Bacterial translocation across an impaired gastrointestinal barrier might be a source for endotoxin 15 16 17 18 19 20 . Gut stunning may explain such a disruption of the gut-mucosal barrier 21 .…”

mentioning

confidence: 99%

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

Lemesch

Ribitsch

Schilcher

et al. 2016

Sci Rep

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Bacterial infection and sepsis are common complications of chronic kidney disease (CKD). A vicious cycle of increased gut permeability, endotoxemia, inadequate activation of the innate immune system and resulting innate immune dysfunction is hypothesized. We assessed endotoxemia, neutrophil function and its relation to oxidative stress, inflammation and gut permeability in patients with CKD grade 3–5 without renal replacement therapy (CKD group, n = 57), patients with CKD stage 5 undergoing haemodialysis (HD, n = 32) or peritoneal dialysis (PD, n = 28) and patients after kidney transplantation (KT, n = 67) in a cross-sectional observational study. In HD patients, endotoxin serum levels were elevated and neutrophil phagocytic capacity was decreased compared to all other groups. Patients on HD had a significantly higher mortality, due to infections during follow up, compared to PD (p = 0.022). Oxidative stress, neutrophil energy charge, systemic inflammation and gut permeability could not completely explain these differences. Our findings suggest that dialysis modality and not renal function per se determine the development of neutrophil dysfunction and endotoxemia in CKD-patients. HD patients are particularly prone to neutrophil dysfunction and endotoxemia whereas neutrophil function seems to improve after KT. Multi-target approaches are therefore warranted to improve neutrophil function and potentially reduce the rate of infections with patients undergoing haemodialysis.

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Reduced Intestinal Permeability Measured by Differently Sized Polyethylene Glycols in Acute Uremic Rats

Cited by 6 publications

References 15 publications

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Intestinal barrier: An interface between health and disease

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

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