Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats.
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.
a School of Medicine and Pharmacology, The University of Western Australia, Harry Perkins Institute for Medical Research, Fiona Stanley Hospital , Murdoch , Western Australia , Australia and Department of Gastroenterology, Women's and Children's Hospital , North Adelaide , South Australia , Australia.
Suzanne
S
Mashtoub
Benjamin
B
Feo
Alexandra L
AL
Whittaker
Kerry A
KA
Lymn
Daniel
D
Martinez-Puig
Gordon S
GS
Howarth
D000818:Animals; D005260:Female; D005472:Fluorouracil / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy*; D009711:Nucleotides / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats
D009711:Nucleotides; D005472:Fluorouracil