Indomethacin-Induced Lesion Modifies Contractile Activity in Rat Small Intestines

Lu, Ya‐Wen; Mizutani, Masatoshi; Neya, Toshiaki; Nakayama, Shinji

doi:10.3109/00365529509093305

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…Furthermore, although there was no significant correlation between transit time and overall RIS, there appeared to be an association between primary (non-consequential) late effects and delayed transit. Our results are in agreement with those of Lu and coworkers [54], who reported that motility changed independently of the degree of severity of mucosal injury in a rat model of indomethacin-induced lesions. These findings are compatible with a mechanism mediated through neurohumoral pathways, rather than by anatomical presence of an injured segment of bowel.…”

Section: Discussionsupporting

confidence: 83%

Localized subclinical radiation enteropathy prolongs intestinal transit time: An experimental study in a rat model

Hauer‐Jensen

Theus

Bradley

et al. 1995

Radation Oncology Invest

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SUMMARY Intestinal dysmotility is a prominent feature of chronic radiation enteropathy. This study addressed the question whether localized radiation enteropathy without anatomical obstruction influences stomach to cecum transit time. Male rats were orchiectomized and a loop of ileum was sutured to the inside of the scrotum. After 3 weeks postoperative recovery, the "scrota1 hernia" containing the transposed intestine was irradiated with 18 twice-daily fractions of 2.8 Gy, or 9 daily fractions of 5.6 Gy orthovoltage X-rays. Control animals were operated and sham-irradiated. Stomach to cecum transit time was assessed 26 weeks after irradiation. A 1-ml bolus of barium suspension was administered by gavage and diagnostic X-ray films were obtained at 0, 1,2,2.5,3,3.5, and 4 hr. Transit time was defined as the time to the first X-ray that showed unequivocal contrast filling of the cecum. Normal range and day-to-day variability were assessed in normal, unoperated control rats. After completion of transit studies, the rats were euthanized, samples from shielded and irradiated intestine were procured, and radiation injury was assessed with a histopathological scoring system. Median stomach to cecum transit time in unoperated controls was 2.25 hr. The surgical procedure and aging did not significantly affect transit time. Transit time was significantly prolonged both in the 2.8 Gy x 18 group (P = 0.02) and in the 5.6 Gy x 9 group (P = 0.0001). The association between histopathologic radiation injury and transit time did not reach statistical significance. We conclude that non-obstructing radiation injury in the distal ileum significantly prolongs intestinal transit time and that small bowel follow-through with barium contrast may be used to assess radiation enteropathy in this animal model. Rudiut Oncol Invest 1995;3:157-166. 0 1995 Wdey-Liss, Inc.

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Section: Discussionsupporting

confidence: 83%

Localized subclinical radiation enteropathy prolongs intestinal transit time: An experimental study in a rat model

Hauer‐Jensen

Theus

Bradley

et al. 1995

Radation Oncology Invest

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“…The application of atropine failed to significantly modify the contractile response to 5-HT in the adult rat small intestine. This observation correlates with previous studies demonstrating that the contractile response to 5-HT was insensitive to antagonism by atropine in the isolated rat ileum and colon [9] . In comparison, pretreatment of the neonatal rat ileum with atropine significantly reduced contractile responses induced by 5-HT, suggesting that the 5-HT-induced contractions are at least partially cholinergically mediated.…”

Section: Discussionsupporting

confidence: 81%

The Involvement of the Serotonergic Transmission System in Neonatal and Adult Rat Ileum Contractility Varies with Age

Lobo¹,

Denyer²,

Britland

et al. 2011

Pharmacology

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The relevance of age on serotonergic involvement in the control of alimentary contractility has not been pharmacologically described. Experiments were performed to investigate the effects of acetylcholine, atropine, 5-hydroxytryptamine (5-HT) and its related drugs on intestinal segments taken from the neonatal and adult ileum. 5-HT induced concentration-dependent contractions of ileum irrespective of age; however, these contractions were diminished by pretreatment with atropine only in neonatal tissues. In tissues taken from both the neonatal and adult ileum, methysergide (5-HT_1/2/5–7 receptor antagonist), ritanserin (5-HT₂ receptor antagonist), and RS23597-190/SB204070 (5-HT₄ receptor antagonists) all differentially reduced 5-HT-induced contractions at a concentration <100 µmol/l. At higher concentrations, the contractions were comparable to those in control tissues. Granisetron and ondansetron (5-HT₃ receptor antagonists) significantly reduced contractions induced by 5-HT at concentrations >30 µmol/l in both neonatal and adult ileum. Combined treatments with ritanserin, granisetron, plus RS23597-190 reduced or abolished contraction responses induced in neonatal ileum by 5-HT. SB269970A (5-HT₇ receptor antagonist) and WAY100635 (5-HT_1A receptor antagonist) failed to influence contractile responses induced by 5-HT or 5-HT receptor agonists. Pretreatments with WAY100635 and SB267790A also had no influence on the contractile responses induced by 5-HT_1A/7 receptor agonist, 5-CT, and 5-HT_1A receptor agonist, 8-OH-DPAT, which itself failed to induce a measurable response. It is concluded that the 5-HT-induced contractions in segments taken from both the neonatal and adult rat ileum were mediated via 5-HT₂ receptors, 5-HT₃ receptors and 5-HT₄ receptors. However, the effect of atropine on the neonatal rat intestine indicates that the mechanism of serotonergic involvement in ileal contractility is influenced by age.

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“…Fioramonti and Bueno (10) reported that decreased amplitude of spike potentials and abolished fasting migrating motor complexes were shown in indomethacin-induced gastric damage. In addition, Lu et al (20) demonstrated that after indomethacin administration, intestinal segments with lesions failed to produce peristaltic activity, whereas in those segments with no visible lesions the peristaltic activity was enhanced. Concerning gastric emptying of Sustacal ® , we were not able to find any difference between control and indomethacin-treated animals, at any time point or doses utilized.…”

Section: Discussionmentioning

confidence: 99%

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Souza

Troncon

Cunha

et al. 2003

Braz J Med Biol Res

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Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg , was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal ® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3%) or INDO-20 (56.1 ± 3.1%) compared to control (45.5 ± 1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal ® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.

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Indomethacin-Induced Lesion Modifies Contractile Activity in Rat Small Intestines

Cited by 14 publications

References 20 publications

Localized subclinical radiation enteropathy prolongs intestinal transit time: An experimental study in a rat model

Localized subclinical radiation enteropathy prolongs intestinal transit time: An experimental study in a rat model

The Involvement of the Serotonergic Transmission System in Neonatal and Adult Rat Ileum Contractility Varies with Age

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

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