aceglutamide-aluminum and Stomach-Ulcer

Severe ulcers were produced in rats by injections of 20% acetic acid in a volume of 0.05 ml into the subserosal layer of two portions in the corpus, and the effects of aceglutamide aluminum on hexosamine, sialic acid, uronic acid and hydroxyproline contents of the mucosa and stroma in the ulcerated regions were compared with the effects of L-glutamine. When aceglutamide aluminum (1,000 mg/kg x 2/day) was orally administered for 4 consecutive days beginning the day of the operation, this drug inhibited the ulcer index and the perforations in ulcerated regions by 18 and 66%, respectively. In addition, the drug remarkably increased the total amounts (microgram/ulcer areas/rat) of hexosamine, sialic acid, and uronic acid in the mucosa of ulcerated regions. It was notable than with the sialic acid contents, an increase in the concentration (microgram/100 mg dry tissue) was also observed. On the other hand, in the stroma of ulcerated regions, the contents of those components containing hydroxyproline were little affected by this drug. Following daily oral administration for 14 consecutive days, aceglutamide aluminum (1,000 mg/kg x 2/day) brought about more potent effects than those following the 4 days administrations, and this drug showed a 37% inhibition of the ulcer index and a complete inhibition of the perforations. Moreover, the drug pronouncedly increased both total amounts and concentrations of hexosamine, sialic acid, and uronic acid in the mucosa in the ulcerated portions. Of these components, the increment of the sialic acid content was the greatest. In the stroma of ulcerated portions, total amounts and concentrations of those components containing hydroxyproline were significantly increased by this drug, although the increase in the stroma were less than those in the mucosa. These effects of aceglutamide aluminum were far more potent than those of L-glutamine at the same dose. From the above results, aceglutamide aluminum may accelerate ulcer repair by potentiating defensive factors through the increases of components forming the mucus and granuloma in ulcerated tissues.

Topics: Acetates; Acetic Acid; Administration, Oral; Aluminum; Animals; Anti-Ulcer Agents; Gastric Mucosa; Glutamine; Hexosamines; Hydroxyproline; Male; Organometallic Compounds; Rats; Sialic Acids; Stomach Ulcer; Uronic Acids

Gastric ulcer induced by the injection of acetic acid (0.025 ml of 20%) into the gastric wall of rats was healed considerably 5 days after the injection of acetic acid. Non-steroidal anti-inflammatory drugs (NSAID) such as aspirin, indomethacin, and phenylbutazone were given consecutively for 5 days, and they exacerbated the ulcer and enlarged the ulcer area. Aspirin caused exacerbation when it was given for the initial 5 days of the ulcer healing process. Phenylbutazone caused exacerbation by the administration for 5 days at the middle stage of the ulcer healing process. In contrast, indomethacin caused exacerbation not only when it was given for the initial 5 days but also when it was given for the middle 5 days. The effect of the antiulcer agent N-acetyl-L-glutamine aluminum complex (KW-110) on the exacerbation was studied. KW-110 at an oral dose of 500 mg/kg inhibited remarkably the exacerbation induced by all of the NSAID used. The development of gastric lesions induced by these NSAID was also prevented by KW-110. Further study was carried out with regard to the influences of KW-110 on the pharmacological properties of NSAID. The results showed no influences of KW-110 on the antiedematous and antipyretic actions of the NSAID.

Topics: Aluminum; Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Drug Interactions; Edema; Fever; Gastric Mucosa; Glutamine; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Stomach Ulcer