Influence of uridine treatment in mice on the protection of gastrointestinal toxicity caused by 5-fluorouracil.
C57B1/6 male normal mice were treated with 5-FU (200 mg/kg i.p.) alone or in combination with a bolus injection of uridine (2 x 3500 mg/kg i.p.) in order to study the potential rescue effect of uridine on 5-FU-induced gastrointestinal toxicity. 5-FU alone inhibited the activity of different enzymes (thymidine-kinase, alkaline-phosphatase, sucrase and maltase) which were selected as the early biochemical markers for the injured small intestinal mucosa. The nadir of the enzyme activities was between 24-96 hrs after 5-FU administration, and the complete regeneration took a week. In the combination of 5-FU plus uridine bolus injection the seriousness of gastrointestinal damage caused by 5-FU was significantly (p < 0.05) milder and the recovery time was shorter by 2 days. Comparing the rescue effect of two dose schedules of uridine, both high dose (2 x 3500 mg/kg) or repeated lower doses of uridine (7 x 800 mg/kg) resulted in a similar protection from the gastrointestinal side effect of 5-FU.
Bagrij
T
T
National Institute of Oncology Budapest, Hungary.
Kralovanszky
J
J
Gyergyay
F
F
Kiss
E
E
Peters
G J
GJ
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology; D007421:Intestine, Small / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000032:analysis; D013045:Species Specificity; D013393:Sucrase / Q000032:analysis; D013937:Thymidine Kinase / Q000032:analysis; D014529:Uridine / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000032:analysis
D015415:Biomarkers; D009363:Neoplasm Proteins; D013937:Thymidine Kinase; D000469:Alkaline Phosphatase; D000520:alpha-Glucosidases; D013393:Sucrase; D005472:Fluorouracil; D014529:Uridine