A non-invasive method to evaluate gastrointestinal transit behavior in rat

Bove, Geoffrey M.

doi:10.1016/j.vascn.2015.04.004

Cited by 15 publications

(16 citation statements)

References 11 publications

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“…Consistent with literature data reporting constipation in patients treated with granisetron as an antiemetic therapy[11,15], we observed an increased time to first defecation, a recognized indicator of whole-gut transit[24,25], after acute administration of granisetron in rats. Granisetron-induced constipation was abolished by in vivo co-administration with ZnPPIX (HO inhibitor), whereas co-administration of hemin (HO-1 inducer) did not decrease the delayed time to first defecation observed in granisetron-treated rats.…”

Section: Discussionsupporting

confidence: 91%

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Carbon monoxide contributes to the constipating effects of granisetron in rat colon

Nacci¹,

Fanelli²,

Potenza³

et al. 2016

WJG

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AIMTo investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron.METHODSFor in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) or CO-releasing molecule-3 (CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment with or without atropine (3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine (L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor).RESULTSAdministration of granisetron (50, 75 μg/kg) in vivo significantly increased the time to first defecation (P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of ZnPPIX or hemin alone had no effect on this gastrointestinal motility parameter, ZnPPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone (3 μmol/L) did not significantly modify the colon’s contractile response to either EFS or ACh. Incubation with ZnPPIX alone (10 μmol/L) significantly reduced the colon’s contractile response to EFS (P = 0.016) but had no effect on contractile response to ACh. Co-administration of ZnPPIX and atropine (3 μmol/L) abolished the ZnPPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3 (400 μmol/L) alone increased both the contractile response to EFS at 10 Hz (10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh (100 μmol/L) (P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnPPIX, the ZnPPIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3 (400 μmol/L) further increased the colon’s contractile response to EFS (at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh (ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFS-induced and ACh-induced contractile response.CONCLUSIONTaken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron.

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Section: Discussionsupporting

confidence: 91%

“…Following drug administration, each rat was monitored every 10 min for 180 min, and the time to first defecation was assumed as an index of whole-gut transit[24,25]. …”

Section: Methodsmentioning

confidence: 99%

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

Nacci¹,

Fanelli²,

Potenza³

et al. 2016

WJG

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“…For example, a colored marker or a small metallic bead is placed in the stomach and the time taken for the first colored fecal pellet or the bead to be expelled is recorded . More recently, a minimally invasive method has been proposed to determine overall GI behavior in isolated animals, from the initiation of eating to waste elimination, by using pigmented food, a cage with a wire mesh floor located above a collection box, and a webcam to record fecal pellet discharge counts …”

Section: Discussionmentioning

confidence: 99%

“…27,28 More recently, a minimally invasive method has been proposed to determine overall GI behavior in isolated animals, from the initiation of eating to waste elimination, by using pigmented food, a cage with a wire mesh floor located above a collection box, and a webcam to record fecal pellet discharge counts. 29 Some researchers study the propulsion time of a bead (to mimic a fecal pellet) inserted in the colon to a certain distance from anus. 30 Other methods include electromyography after attaching electrodes to the serosa, or pressure recording using a balloon inserted in the stomach or the colon.…”

Section: Discussionmentioning

confidence: 99%

X‐ray analysis of gastrointestinal motility in conscious mice. Effects of morphine and comparison with rats

Girón

Pérez-García

Abalo

2015

Neurogastroenterology Motil

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Background Non‐invasive methods to study gastrointestinal (GI) motility are of high interest, particularly in chronic studies. Amongst these, radiographic techniques after contrast intragastric administration may offer many advantages. In previous studies, we have successfully and reproducibly applied these techniques together with a semiquantitative analysis method to characterize the effect of different drugs, acutely or repeatedly administered in rat models, but we have never before used these techniques in mice. These are very convenient in basic research. Our aim was to determine if our method is also valid in mice. Additionally, we determined the effect of morphine on GI motor function in both species. Methods Animals received an intraperitoneal administration of morphine (at 10 and 5 mg/kg for rats and mice, respectively). Twenty min later, barium contrast (at 2 g/mL) was gavaged (2.5 and 0.4 mL for rats and mice respectively) and serial X‐rays were obtained 0–8 h after contrast. X‐rays were analyzed as previously described, using a semiquantitative score to build motility curves for each GI region. Key Results Motility was much faster in mice than in rats for all GI regions. Morphine at the doses used significantly depressed motility in both species to a similar extent if the whole gut or the upper GI regions (stomach, small intestine) were considered, although its effect seemed to be more intense in the lower GI regions (caecum, colorectum) in rats than in mice. Conclusions & Inferences We have validated our X‐rays method for its use in mice.

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“…We evaluated postoperative ileus by observing fecal discharge, using methods previously described [28]. Discharge over 4 hour epochs was chosen as the outcome measure.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of postoperative adhesions using a modeled manual therapy

Bove

Chapelle²,

Hanlon

et al. 2017

PLoS ONE

Self Cite

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Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

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A non-invasive method to evaluate gastrointestinal transit behavior in rat

Cited by 15 publications

References 11 publications

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

X‐ray analysis of gastrointestinal motility in conscious mice. Effects of morphine and comparison with rats

Attenuation of postoperative adhesions using a modeled manual therapy

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