Prophylactic Effect of L-Glutamine against Intestinal Derangement Induced 5-Fluorouracil or Indomethacin in Rats.

Accession number;02A0602768
Title;Prophylactic Effect of L-Glutamine against Intestinal Derangement Induced 5-Fluorouracil or Indomethacin in Rats.
Author;TANAKA AKIKO(Kyoto Pharm. Univ.)   TAKEUCHI KOJI(Kyoto Pharm. Univ.)   
Journal Title;Japanese Pharmacology & Therapeutics
Journal Code:Z0947A
ISSN:0386-3603
VOL.30;NO.6;PAGE.455-462(2002)
Figure&Table&Reference;FIG.8, REF.17
Pub. Country;Japan
Language;Japanese
Abstract;We examined the prophylactic effect of L-glutamine on the morphological and functional derangement of rat small intestine after administration of 5-fluorouracil (5-FU) or indomethacin. Male SD rats were used without fasting. In the first study, the animals were given 5-FU s.c. at 200mg/kg as a single injection,and killed 4 days later. L-glutamine (1 and 3g/kg) was given p.o. once daily for 5 days, starting 1 day before 5-FU. In the second study, 5-FU (100 mg/kg) was given repeatedly once daily for 5 days, without or with L-glutamine (1g/kg), and the animals were killed 24 hr after the final administration. In the third study, the animals were given indomethacin (10mg/kg) s.c., and killed 24 hr later. L-glutamine (1 and 3g/kg) was given once daily for 4 days, starting 3 days before indomethacin. Administration of 5-FU caused a marked decrease in body weight and the villus height in jejunum mucosa as well as an increase in intestinal microvascular permeability, the degree of these changes being more pronounced after the repeated administration. Supplementation of L-glutamine dose-dependently and significantly reverted these changes induced by a single injection of 5-FU, hut provided a significant effect only against the decrease in villus height, in case of the repeated administration of 5-FU. Histological observation revealed that 5-FU decreased the number of goblet cells, and supplementation of L-glutamine apparently reversed the decrease of goblet cells induced by 5-FU. On the other hand, pretreatment of the animals. with L-glutamine provided a dose-dependent protection against indomethacin-induced intestinal damage, the effect being significant at 3g/kg/day. These results suggest that supplementation of L-glutamine is effective in preventing the morphological and functional derangement of small intestine caused by 5-FU or indomethacin. (author abst.)