The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings

Schreiber, D; Klotz, Markus; Laures, Kerstin; Clasohm, Jasmin; Bischof, Michael; Schäfer, Karl‐Herbert

doi:10.1016/j.aanat.2014.02.008

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…Correspondingly norepinephrine that was used as first line vasopressor also had to be given in higher dosage when defecation pattern was inadequate. These findings are in concordance to literature where an association between sedatives, analgesics (especially opioids) and vasopressors and constipation is described [5,7,[24][25][26]. All these drugs are well-known to impair gut motility in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 81%

Frequency of Disturbed Defecation Pattern in Neurosurgical Critically Ill Patients and Influence on Intracranial Pressure and Intensive Care Treatment

Kieninger¹,

Finzel²

2015

J Anesth Clin Res

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Section: Discussionsupporting

confidence: 81%

Frequency of Disturbed Defecation Pattern in Neurosurgical Critically Ill Patients and Influence on Intracranial Pressure and Intensive Care Treatment

Kieninger¹,

Finzel²

2015

J Anesth Clin Res

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“…29 But its application to experimental animals, particularly rodents, like many other techniques, requires the use of anesthesia, which may interfere with intestinal motility. 7,8 Fluoroscopy (continuous radiographic recording), which also offers functional and morphologic data, may be a good alternative to study intestinal motility in vivo in conscious animals.…”

Section: Discussionmentioning

confidence: 99%

“…The less invasive methods are more adequate to mimic the clinical situation, but anesthetics or sedative drugs are often used, particularly in small laboratory animals, and these drugs can interfere with gastrointestinal motility. 7,8 Previously, radiographic methods have been used combined with a simple semiquantitative analysis that allow the use of conscious rats to study the effect of different drugs administered either acutely or chronically, including opioids 9 and cannabinoids, 10,11 on general gastrointestinal motor function. Interestingly, spatio-temporal maps (STM), similar to those used previously to characterize motor function of isolated segments of the gut in organ bath experiments, [12][13][14] were applied to analyze small intestinal contractility from fluoroscopic recordings obtained in vivo from conscious rats.…”

Section: Introductionmentioning

confidence: 99%

Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats

Díaz-Ruano

López‐Pérez

Girón

et al. 2019

J Neurogastroenterol Motil

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Background/Aims Gastrointestinal adverse effects have a major impact on health and quality of life in analgesics users. Non-invasive methods to study gastrointestinal motility are of high interest. Fluoroscopy has been previously used to study gastrointestinal motility in small experimental animals, but they were generally anesthetized and anesthesia itself may alter motility. In this study, our aim is to determine, in conscious rats, the effect of increasing doses of 2 opioid (morphine and loperamide) and 1 cannabinoid (WIN 55,212-2) agonists on colonic motility using fluoroscopic recordings and spatio-temporal maps. Methods Male Wistar rats received barium sulfate intragastrically, 20-22 hours before fluoroscopy, so that stained fecal pellets could be seen at the time of recording. Animals received an intraperitoneal administration of morphine, loperamide, or WIN 55,212-2 (at 0.1, 1, 5, or 10 mg/kg) or their corresponding vehicles (saline, Cremophor, and Tocrisolve, respectively), 30 minutes before fluoroscopy. Rats were conscious and placed within movement-restrainers for the length of fluoroscopic recordings (120 seconds). Spatio-temporal maps were built, and different parameters were analyzed from the fluoroscopic recordings in a blinded fashion to evaluate colonic propulsion of endogenous fecal pellets. Results The analgesic drugs inhibited propulsion of endogenous fecal pellets in a dose-dependent manner. Conclusions Fluoroscopy allows studying colonic propulsion of endogenous fecal pellets in conscious rats. Our method may be applied to the noninvasive study of the effect of different drug treatments and pathologies.

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“…Long-time motility heatmaps were generated as described previously by Schreiber et al ( 2014 ) only to evaluate the quality of the perfusion. Motility could be kept constant for at least 5 h.…”

Section: Methodsmentioning

confidence: 99%

“…Due to their specific advantages, in vitro models with intestinal segments are widely used for research in intestinal physiology and pharmacology. Recently, more complex in vitro perfusion approaches have been described by several groups for the analysis of drug-effects on motility (Lautenschlager et al, 2010 ; Alam et al, 2012 ; Schreiber et al, 2014 ). Due to the ENS's ability to control most intestinal functions autonomously, intestinal segments can keep some of their normal physiological functions in vitro without CNS support.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

et al. 2017

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Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

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The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings

Cited by 11 publications

References 31 publications

Frequency of Disturbed Defecation Pattern in Neurosurgical Critically Ill Patients and Influence on Intracranial Pressure and Intensive Care Treatment

Frequency of Disturbed Defecation Pattern in Neurosurgical Critically Ill Patients and Influence on Intracranial Pressure and Intensive Care Treatment

Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

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