May cannabinoids prevent the development of chemotherapy‐induced diarrhea and intestinal mucositis? Experimental study in the rat

Abstract

Background The antineoplastic drug 5‐fluoruracil (5‐FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5‐FU‐induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5‐FU in the rat. Methods Male Wistar rats received vehicle or the non‐selective cannabinoid agonist WIN 55,212‐2 (WIN; 0.5 mg kg−1 injection−1, 1 injection day−1, 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5‐FU (150 mg kg−1 injection−1, cumulative dose of 300 mg kg−1). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. Key Results As shown radiographically, 5‐FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5‐FU‐treated animals but tended to reduce the severity of 5‐FU‐induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5‐FU‐treated animals. 5‐FU‐induced mucositis was severe and not counteracted by WIN. Conclusions and Inferences 5‐FU‐induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy‐induced diarrhea.

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

“…Taranabant increased the number of bowel movements after systemic and oral administration and significantly increased fecal pellet output in mice with constipation induced by ipratropium (Fichna et al, 2013). It has been demonstrated that a low dose of a non-selective cannabinoid agonist WIN55,212-2 reduced the severity of 5-fluorouracil-induced diarrhea in rats (Abalo et al, 2016). …”

Editorial: Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae?

“…Interestingly, using radiographic methods in rats, Vera et al showed that a CB1 receptor cannabinoid antagonist prevented the effect of acute vincristine on gastrointestinal motility, particularly in the small intestine. Thus, inactivation of the cannabinoid system might be useful to counteract CIC, whilst cannabinoid receptor activation might be used to counteract CID (Abalo et al, 2017 ; McQuade et al ).…”

Chemotherapy Induced Diarrhea: A Case Report

“…As we have discussed above, the genesis of chemotherapy induced diarrhea is believed a complicated process resulting from combination and interaction of multiple factors including gene mutation and enzyme deficiency, intestinal mucosa inflammation, dysbacteriosis as well as nervous system disability. However, there are still puzzles and questions in all of the possible mechanisms [33][34][35][36][37]. Medications towards these mechanisms still cannot work very well in quite a number of cases.…”