In Vitro Effects of Wood Creosote on Enterotoxin-Induced Secretion Measured Electrophysiologically in the Rat Jejunum and Colon.

Abstract

Wood creosote, a mixture of guaiacol, creosol and related phenolic compounds, has been used in Japan as a traditional drug for the treatment of diarrhea for more than a century. 1)However, only during the last decade, have the mechanisms of antidiarrheal action of wood creosote become the subject of thorough investigation. The therapeutic effect of wood creosote was first linked to its ability to reduce intestinal motility. 2,3) In addition, an antisecretory and/or pro-absorptive effect of wood creosote was suggested by findings in animal models of diarrhea. Wood creosote was found to prevent castor oil-induced diarrhea in rats 4) and to reduce fluid secretion induced by an Escherichia coli (E. coli) enterotoxin applied into loops of rabbit jejunum in vivo. 5) In previous studies, using in vitro electrophysiologic measurements of electrogenic ion transport in isolated intestinal mucosal sheets, we demonstrated that, while having a moderate effect on basal secretion, wood creosote completely inhibited secretory responses to exogenous acetylcholine. 6,7) The goal of the present investigation was to extend our knowledge about the mechanism of antisecretory action of wood creosote using an in vitro model of enterotoxin-induced hypersecretory conditions. Since secretory diarrhea occurs when the balance between intestinal absorption and secretion is disturbed by excessive secretion caused by enterotoxins produced by the pathogen, we consider the experiments relevant to the clinical cases of infectious secretory diarrhea. The active net electrogenic transport was measured electrophysiologically as the short circuit current passed via a voltage clamp to eliminate the transmucosal potential difference. MATERIALS AND METHODS AnimalsMale Sprague-Dawley rats (body weight 250-300 g) were used in the experiments. The animals were purchased from Charles River Laboratories (Wilmington, Massachusetts, U.S.A.) and were housed under standard conditions (21°C and a 12-h light/dark cycle) at the animal facility for at least one week prior to initiating the experiments. On the day of experiment the rats were killed by decapitation and the jejunum and mid portion of the colon were immediately removed and placed in aerated ice-cold Krebs solution. The experimental protocol of the study was approved by the Oklahoma City V.A. Medical Center Animal Care Committee.Electrophysiological Measurement of Net Electrogenic Transport Small intestinal and colonic segments (20 mm long) were used for the preparation of mucosal sheets as described previously.7) Muscle-stripped mucosal sheets were placed in modified Ussing chambers (0.6 cm 2 exposed surface area) that were filled with Krebs bicarbonate buffer (pH 7.2), containing 10 mM mannitol on the mucosal (intraluminal) side and 10 mM glucose at the serosal side. The lack of glucose at the intraluminal side avoided alterations in mucosal transport due to glucose absorption. The Krebs buffer was maintained at 37°C and was continuously aerated with 95% O 2 and 5% CO 2 . An equilibration period of at ...

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats

“…Thus, zingerone seems to be beneficial for patients with colonic disorder related to hyperexcitability of smooth muscles. In support of this notion, it has been reported that some antidiarrheal drugs, such as loperamide and wood creosote, possess inhibitory effects on gut motility in addition to their modulatory effects on fluid absorption/secretion [30][31][32][33][34]. These agents can act directly on intestinal smooth muscles [35,36], being consistent with our results.…”

Inhibition of Rat Intestinal Cl^– Secretion by 4,5-Dimethylresorcinol

“…This finding is consistent with the notion that LT and STa induce electrogenic Cl -secretion from intestinal epithelial cells [13,25,36]. The LT-and STa-induced increases in I sc were also inhibited by wood creosote applied to the serosal surface in a dose-dependent fashion; i.e., the IC 50 s were 0.4 and 4.5 Ìg/ml, respectively [38]. The results of Greenwood-Van Meerveld et al [30] strongly suggest that wood creosote inhibits CFTR and confirm our findings.…”

“…This acetylcholineinduced increase in I sc [37] was inhibited by the addition of wood creosote to the serosal surface and the IC 50 was calculated to be 10 Ìg/ml [30]. These researchers also reported that LT and STa increased the I sc when added to the mucosal surface in the absence of acetylcholine [38]. This finding is consistent with the notion that LT and STa induce electrogenic Cl -secretion from intestinal epithelial cells [13,25,36].…”

Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli

“…Kuge et al . (2001) using Ussing chambers with rat jejunum and colon and LT and STa toxins observed an antisecretory activity in the small intestine, against LT-induced secretion [95]. The secretion inhibition was more potent following serosal application whereas in the colon it inhibited STa-induced secretion with equal potency following serosal or mucosal addition.…”

“…Overall, the antisecretory effect is independent of the intracellular pathway activated by the enterotoxin since wood creosote inhibited both cAMP- and cGMP-mediated secretion induced by LT or STa, respectively [95]. Wood creosote may diminish the secretion induced by the interaction of bacterial enterotoxin with both epithelial cells and enteric neurons.…”