naphthoquinones and Ileus

Patients undergoing an abdominal surgical procedure develop a transient episode of impaired gastrointestinal motility or postoperative ileus. Importantly, postoperative ileus is a major determinant of recovery after intestinal surgery and leads to increased morbidity and prolonged hospitalization, which is a great economic burden to health-care systems. Although a variety of strategies reduce postoperative ileus, including multimodal postoperative rehabilitation (fast-track care) and minimally invasive surgery, none of these methods have been completely successful in shortening the duration of postoperative ileus. The aetiology of postoperative ileus is multifactorial, but insights into the pathogenesis of postoperative ileus have identified intestinal inflammation, triggered by surgical handling, as the main mechanism. The importance of this inflammatory response in postoperative ileus is underscored by the beneficial effect of pharmacological interventions that block the influx of leukocytes. New insights into the pathophysiology of postoperative ileus and the involvement of the innate and the adaptive (T-helper type 1 cell-mediated immune response) immune system offer interesting and important new approaches to prevent postoperative ileus. In this Review, we discuss the latest insights into the mechanisms behind postoperative ileus and highlight new strategies to intervene in the postoperative inflammatory cascade.

Topics: Adaptive Immunity; Ghrelin; Humans; Ileus; Immunity, Innate; Inflammation; Naphthoquinones; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists

Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI).. The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B.. Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner.. Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.

Topics: Acrolein; Amides; Animals; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Transit; Ileus; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Naphthoquinones; Organ Culture Techniques; TRPA1 Cation Channel