Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats

Abstract

Chemotherapy-induced mucositis is characterized by inflammation and ulceration of the intestinal mucosa, compromising intestinal function. Exogenous nucleotides have been reported to repair the mucosa. The nucleotide preparation, Nucleoforce F0328 (Nucleoforce), was investigated for its potential to ameliorate intestinal mucositis in rats. Female Dark Agouti rats (n = 8/group) were gavaged once daily with Nucleoforce (175 mg/kg) or water from Days 0 to 8 and injected (i.p.) with 5-fluorouracil (5-FU; 150 mg/kg) or saline on Day 5. Histological parameters (disease severity, crypt depth, and villus height measurements) and myeloperoxidase activity were quantified. P < 0.05 was considered significant. Jejunal and ileal histological disease severity scores were significantly increased by 5-FU, compared to normal controls (P < 0.05). Nucleoforce treatment in 5-FU-injected rats significantly reduced jejunal and ileal disease severity compared to 5-FU controls (P < 0.05). In 5-FU-injected rats, jejunal and ileal villus heights and crypt depths were significantly decreased compared to 5-FU controls, with no additional Nucleoforce effect (P > 0.05). Intestinal myeloperoxidase activity was significantly elevated by 5-FU (8.8-fold), compared to normal controls (P < 0.05), which was not normalized by Nucleoforce treatment (P > 0.05). Nucleoforce only partially improved parameters associated with experimentally-induced mucositis. Future studies could investigate increased concentrations, more frequent administration, or protective microencapsulation delivery methods, to increase bioavailability.

Emu Oil Combined with Lyprinol™ Reduces Small Intestinal Damage in a Rat Model of Chemotherapy-Induced Mucositis

“…Decreased intestinal length may aid in maintaining mucosal integrity to protect against translocation of pathogens into the submucosa 7,12 . Furthermore, 5-FU resulted in decreased thymus and spleen weights, similar to previous studies using 5-FU 14,17,18,42 .…”

Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

“…This is presumably due to the increased cell-turnover rate which is a characteristic feature of the small intestine[ 3 ]. The main histological findings of villus shortening and crypt disruption caused by 5-FU administration were typical, and in concordance with other studies[ 27 - 29 ].…”

“…Patient symptoms arising as a result of the barrage of pathophysiological changes occurring in the alimentary tract in mucositis typically include reduced food consumption, and hence body weight decrease[ 29 , 31 ]. Clinical features in the current study were classic although we observed increased urine output in the absence of polydipsia.…”

Neuroimmunological complications arising from chemotherapy‐induced gut toxicity and opioid exposure in female dark agouti rats

“…The weight loss and increased intestinal MPO expression following 5-FU administration confirmed that this model induced gut toxicity in rats. In accordance with the previous works from which these tissues were scavenged, acute intestinal inflammation was identified by significant increases in jejunal and ileal MPO expression following 5-FU administration (see the following published works for other phenotypic and characteristic parameters studied (Mashtoub et al, 2013(Mashtoub et al, , 2015Wang et al, 2017)). CAR administration was associated with attenuated acute intestinal inflammation in the jejunal and ileal regions of rats with 5IGT.…”