Validation of 13C-Acetic Acid Breath Test by Measuring Effects of Loperamide, Morphine, Mosapride, and Itopride on Gastric Emptying in Mice

Abstract

The 13 C-breath test is used in clinical diagnosis of gastric emptying disorders. The gastric emptying rate can be assessed easily by breath tests using a 13 C isotope-labeled substance.1) The orally administered 13 C-labeled substance is not absorbed in the stomach, but rapidly absorbed in the duodenum and then metabolized in the liver to be released as 13 CO 2 . Therefore, the 13 C-breath test reflects gastric emptying rates and can monitor time-dependent changes in gastric motility in humans.Most rat or mouse tests currently used for measuring gastrointestinal motility are non-survival procedures that measure the passage of a solid meal or marker such as phenol red or beads. These conventional methods require time-restricted excision of the stomach and analysis of the remaining test meal in the stomach. Thus, the data obtained from these methods are limited to only one time parameter per animal (fixed time intervals). A repetitive and non-invasive method of measuring gastric emptying in rodents would be useful for investigating alterations over time of whole animal gut function in disease states. Recently, a variety of non-invasive methods to measure gastric emptying in rodents have been reported using scintigraphy 2,3) and magnetic resonance imaging (MRI). 4) However, these models require physical restraint of the animal, trained personnel, and expensive analytical equipment.The 13 C-breath test is a non-invasive method that can be used without physical restraints in rodents. Symonds et al. 5,6) and Schoonjans et al. 7) reported a breath test for evaluating gastric emptying in rodents using 13 C substrates such as octanoic acid and acetic acid. In these reports, gas chromatography or mass spectrometry was used to analyze the expired 13 CO 2 levels. However, the protocols of these experiments are complicated, and air exchange must be prevented during the sampling of expired 13 CO 2 . Uchida et al. modified the 13 C-breath test using rats and established a simple system using a desiccator and pump along with an infrared red spectrometer.8) This method is a simple and non-invasive method for measurement of gastric emptying without causing rats stress. With this method, 13 C-acetic acid was found to be more sensitive for monitoring gastric emptying than 13 Coctanoic acid.9) This test can successfully evaluate gastric emptying and can be used to study gastric prokinetics in the models of gastric motility disorders.The 13 C-breath test will be useful as a new tool to investigate the effects of drugs on gastric motility for further development. Recently, the use of mouse models has increased in gastrointestinal research. However, there are few studies evaluating the effects of clinically effective drugs that affect gastric motility using the 13 C-breath test in rodents. In this study, we adopted this non-invasive and accurate method to investigate the effects of drugs that affect gastric motility in mice. Loperamide and morphine were used to inhibit gastric motility in mice. Loperamide is an effective agonist for d...

The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans

“…This test is an accurate, noninvasive, simple method, without radiation exposure, and represents a reliable alternative to scintigraphy, the gold standard for measuring gastric emptying (4,34). Test solutions were labeled with 50 mg of [ 13 C]sodium acetate, which is rapidly absorbed in the duodenum, transported to the liver, and metabolized to 13 CO2 (22). Subjects were asked to exhale through a mouthpiece to collect an end-expiratory breath sample into a 100-ml foil bag.…”

Dual Role of Mosapride Citrate Hydrate on the Gastric Emptying Evaluated by the Breath Test in Conscious Rats

“…On the other hand, 13 C-breath tests have been developed recently as a nonradioactive alternative in clinical study. The 13 C-labeled urea breath test, in particular, has been widely employed clinically to monitor Helicobacter pylori infections.…”

“…The 13 C-labeled urea breath test, in particular, has been widely employed clinically to monitor Helicobacter pylori infections. In addition, the [1-…”

“…We recently reported a simple and non-invasive breath test for evaluating gastric emptying using [1][2][3][4][5][6][7][8][9][10][11][12][13] C]acetic acid (10) (10 -13). Then, in this study we investigated the dosage effect of mosapride (5-HT 4 receptor agonist) and time course of the gastric emptying using the breath test with [1-13 C] acetic acid.…”

Simultaneous measurement of gastric emptying and gastrocecal transit times in conscious rats using a breath test after ingestion of [1-¹³C] acetic acid and lactose-[¹³C] ureide

“…In basic research, we have already reported a simple and non-invasive breath test system for evaluating gastric emptying and pancreatic exocrine secretion in conscious rats (Uchida et al, 2005;Uchida et al, 2007;Uchida et al, 2008;Matsumoto et al, 2008;Uchida et al, 2011). Moreover, we have also established a non-invasive and feasible method for the evaluation of rat gastrocecal transit time by using lactose-[ 13 C] ureide (Uchida et al, 2009a) and the effect of atropine sulfate which significantly delayed the gatsrocecal transit time (Uchida et al, 2009b).…”