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


CONCLUSIONS
(1) A very complex extra- and intracellular feedback mechanism system exists in the gastric mucosa during IND, IND + vitamin A, and IND + beta-carotene treatments; (2) The gastric mucosal preventive effect of vitamin A and beta-carotene only partly depend on their scavenger properties.
Mózsik
G
G
First Department of Medicine, University Medical School of Pécs, H-7643, Pécs, Ifjúság u.13, Hungary. Mozsik@clinics.pote.hu
Rumi
G
G
Bódis
B
B
Figler
M
M
Király
A
A
Sütõ
G
G
Vincze
A
A