Effects of indomethacin, with vitamin A or β-carotene, on the rat gastric mucosa: Extra- and intracellular membrane-bound ATP mechanisms

Gy Mozsik, Gy Rumi, B. Bodis, M. Figler, A. Kiraly, G. Suto, A. Vincze

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Background. Indomethacin (IND) is a widely used non-steroidal anti- inflammatory agent in the treatment of various inflammatory disorders, which causes gastrointestinal injury in humans and animal experiments. Vitamin A and β-carotene prevent the IND-induced gastric mucosal injury. These compounds modify the membrane-bound ATP-dependent energy systems. The aims of this investigation were: (1) To study the IND-induced gastric mucosal damage and its prevention by vitamin A and β-carotene; (2) to measure the biochemical compounds of the gastric mucosa {ATP, ADP, ATP/ADP, AMP, ATP+ADP+AMP, 'energy charge' (ATP + 0.5 ADP)/(ATP+ADP+AMP), cAMP, lactate} under the circumstances mentioned above; (3) to analyze the extra- and intracellular regulatory mechanisms between the membrane-bound ATP-dependent energy systems. Methods. The observations were carried out with CFY (Sprague- Dawstrein rats, weighing 180-210 g). The gastric mucosal damage was produced by IND (20 mg/kg sc. administration) and it was prevented by vitamin A (or β-carotene), given in doses of 0.01-0.1 to 1.0-10.0 mg/kg ig. Different biochemical compounds (ATP, ADP, AMP, cAMP, lactate) and parameters (ATP/ADP, adenylate pool, 'energy charge') were measured and calculated. Results. (1) Vitamin A and β-carotene prevented dose-dependently the IND-induced gastric mucosal damage; (2) the extent of ATP-ADP transformation was increased significantly, while the ATP-cAMP decreased in the gastric mucosa after IND- treatment; (3) vitamin A and β-carotene enhanced the extent of ATP-cAMP transformation, while the ATP-ADP transformation was inhibited (the actions were dose-dependent responses); (4) No change was found in 'energy charge' by IND, while its value decreased significantly with vitamin A and β-carotene. Conclusions. (1) A very complex extra- and intracellular feedback mechanism system exists in the gastric mucosa during IND, IND + vitamin A, and IND + β-carotene treatments; (2) The gastric mucosal preventive effect of vitamin A and β-carotene only partly depend on their scavenger properties.

Original languageEnglish
Pages (from-to)287-295
Number of pages9
JournalInflammoPharmacology
Volume7
Issue number3
DOIs
Publication statusPublished - Jan 1 1999

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Keywords

  • Adenosine nucleotides
  • Cellular energy systems
  • Gastric mucosal injury and prevention
  • Indomethacin
  • Vitamin A
  • β-carotene

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

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