Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron

Abstract

Background Cisplatin is a highly emetogenic antineoplastic drug and induces peripheral neuropathy when given in cycles. Granisetron, a 5‐HT3 antagonist, is clinically used to prevent chemotherapy‐induced nausea/emesis and abdominal pain in irritable bowel syndrome. The effects of cisplatin on visceral sensitivity and those of granisetron in the context of cancer chemotherapy are not well known. Methods Adult male Wistar rats received two intraperitoneal injections 30 minutes apart: granisetron (1 mg kg−1)/vehicle and cisplatin (6 mg kg−1)/vehicle. Thereafter, nausea‐like behavior was measured as bedding intake for 4 hours, and gastric dysmotility was measured radiographically for 8 hours. Gastric weight and size were determined ex vivo and samples of the forestomach, corpus, ileum, and colon were obtained for histological analysis at 4 and 30 hours after cisplatin/vehicle. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation 2 hours after cisplatin/vehicle. Key Results Cisplatin‐induced bedding intake and gastric dysmotility, and granisetron blocked these effects, which occurred in the absence of frank mucositis. Visceral sensitivity was reduced to a similar extent by both drugs alone or in combination. Conclusions and Inferences Cisplatin‐induced bedding intake and gastric dysmotility were blocked by granisetron, confirming the involvement of serotonin acting on 5‐HT3 receptors. Unexpectedly, visceral sensitivity to colonic distension was reduced, to the same extent, by cisplatin, granisetron, and their combination, suggesting important mechanistic differences with nausea and gastric dysmotility that warrant further investigation.

Changes in the diet composition of fatty acids and fiber affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: In vivo and in vitro studies

“…Radiographic images were developed (Kodak X‐omat 2000 automatic processor, Kodak AG), and changes in GI motility were semiquantitatively assessed according to Table S1. Evaluation was made based on the labeled area of the stomach, small intestine, cecum, and the distal colon (fecal pellets) in each X‐ray …”

Radiographic dose‐dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea‐like behavior

“…After loperamide, nausea and vomiting may occur, even when used at therapeutic doses for diarrhea treatment . Rodents lack the motor reflex of emesis but, in response to emetogenic stimuli, display pica, an aversive/illness atypical feeding behavioral response that results in the ingestion of non‐nutritive substances, like clay or the bedding in their cages . The magnitude of pica in rats was directly related to the “emetogenic potential” of antineoplastic drugs in humans .…”

“…The X‐ray images were also digitized and analyzed with the aid of an image analysis system (Image J 1.38 for Windows; National Institute of Health, free software: http://rsb.info.nih.gov/ij/), and the alterations in size and barium density within the stomach, cecum, and fecal pellets were quantitatively analyzed, using the metallic block as reference (its length for morphometry; its color intensity as 100% density). These alterations could indicate wall mechanical changes (that could alter mainly size) or modifications in hydration of luminal contents (that could alter mainly density of contrast).…”

“…The number of times the rat ingested bedding in its cage was recorded in periods of 1 hour by a blinded observer. Food and water intakes were also recorded in the same manner …”

“…In this context of growing public health concern and scientific interest in loperamide, the aim of this research was to assess in the rat the dose‐dependent effects of loperamide on gastrointestinal motor function by non‐invasive radiographic means and relate these to the occurrence of different kinds of central effects and bedding intake (a kind of pica, as a surrogate marker of nausea in rodents).…”