Gastric mucosal preventive effects of prostacyclin and β-carotene, and their biochemical effects in rats treated with ethanol and HCl at different doses and time intervals after administration of necrotizing agents
Prostacyclin (PGI2) and β-carotene have a key role in gastric mucosal defence against endogenous or exogenous noxious agents. Prostacyclin has appreciable protective effects on the gastrointestinal (GI) mucosa, while β-carotene (as one of the retinoid compounds) has oxyradical scavenging properties.
Gastric mucosal damage affected by oral administration of 0.6 mol/L HCl (representing an acid-dependent model) and 96% ethanol (EtOH) (as a non-acid-dependent model);
PGI2-induced (ED50=5 μg/kg po) and β-carotene-induced (ED50=1 mg/kg po) gastroprotection on the gastric mucosal damage produced by HCl and EtOH at different times and doses.
Sprague-Dawley rats were used. After 24 h starvation (with tap water ad libitum), gastric mucosal damage was induced by oral administration of 1 ml 0.6 mol/L HCl or 96% EtOH. Rats were pretreated with oral saline, PGI2 (5 and 50 μg/kg) and β-carotene (1 and 10 mg/kg) and killed at 0, 1, 5, 15, 30 and 60 min after administration of the necrotizing agents. The number and severity of gastric mucosal lesions, measurement of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), lactate (enzymatically), and cyclic adenosine monophosphate (cAMP) by RIA were carried out at different time intervals, after the necrotizing agents were administered. The ratio of ATP/ADP, adenylate pool (ATP+ADP+AMP) and ‘energy charge’ [(ATP+0.5 ADP)/(ATP+ADP+AMP)] were calculated.
The mucosal damage (number and severity) reached about 50% of that obtained 60 min after administration of the necrotizing agents in both models;
PGI2 prevented in the early period (0–15 min), while β-carotene inhibited in the later period (15–60 min) the gastric mucosal damage produced by EtOH and HCl;
The ATP-ADP transformation was decreased in the first (early; 0–15 min) by PGI2 and in the late period (15–60 min) by β-carotene;
ATP-cAMP transformation was increased in the early period by PGI2 and in the late phase by β-carotene;
No significant change was obtained in the ‘energy charge’ and lactate by PGI2 or β-carotene administration;
The changes in adenine nucleotides were the same in the EtOH or HCl models with and without treatment with PGI2 and β-carotene; however, the mucosal protective action of PGI2 and β-carotene, and the energy metabolism, differed significantly dependent on dose and time after
The development of gastric mucosal damage and its prevention can be discriminated into early and late phases;
The early phase of gastric mucosal damage can be prevented by PGI2, and the late phase by β-carotene;
The β-carotene effect only partly depends on its presumptive scavenging properties; and
PGI2 prevents the development of gastric mucosal damage, while β-carotene stimulates the repair mechanisms.
Keywordsacid-dependent gastric ulcer non-acid-dependent gastric ulcer prostacyclin β-carotene cellular energy systems early and late phase of gastric mucosal damage repair mechanisms
Unable to display preview. Download preview PDF.
- 1.Mózsik Gy, Fiegler M, Nagy L, Patty I, Tárnok F. Gastric and small intestinal energy metabolism in mucosal damage. In: Mózsik Gy, Hänninen O Jávor T, eds Gastrointestinal Defense Mechanisms. Oxford and Budapest: Pergamon Press and Akademiai Kiadó.; 1980:213–76.Google Scholar
- 6.Szabó S, Mózsik Gy, eds. New Pharmacology of Ulcer Disease. New York: Elsevier Science Publishers; 1987.Google Scholar
- 7.Jávor T, Bata M, Lovász L et al. Gastric cytoprotective effects of vitamin A and other carotenoids. Int J Tiss React. 1983;5:289–93.Google Scholar
- 8.Mózsik Gy, Móron F, Fiegler M et al. Membrane-bound ATP-dependent energy systems and gastric cytoprotection by prostacyclin, atropine and cimetidine. Int J Tiss React. 1983;5:263.Google Scholar
- 10.Mózsik Gy, Garamszegi M, Jávor T et al. Correlations between the oxygen free radicals, membranebound ATP-dependent energy system in relation to development of ethanol- and HCl-induced gastric mucosal damage and of β-carotene-induced gastric cytoprotection. In: Tsuckiya M, Kawai K, Konda M, Yoshikawa T, eds. Free Radicals in Digestive Diseases Amsterdam: Elsevier Science Publishers; 1988;111–16.Google Scholar
- 11.Mózsik Gy, Garamszegi M, Fiegler M et al. Mechanisms of gastric injury in the stomach. I Time sequence analysis of gastric mucosal membrane-bound ATP-dependent energy system, oxygen-free radicals and appearance of gastric mucosal damage. In: Hayaishi O, Niki E, Kondo M, Yoshikawa T, eds. Medical, Biomedical and Chemical Aspects of Free Radicals. Amsterdam: Elsevier Science Publishers; 1989:1427–31.Google Scholar
- 12.Mózsik Gy, Fiegler M, Garamszegi M et al. Mechanisms of gastric injury in the stomach. I. Time sequence analysis of gastric mucosal membrane-bound ATP-dependent energy system, oxygen-free radicals and macroscopic appearance of gastric cytoprotection by PGI2 and β-carotene in HCl-model of rats. In: Hayaishi O, Niki E, Kondo, M, Yoshikawa T, eds. Medical, Biomedical and Chemical Aspects of Free Radicals. Amsterdam: Elsevier Science Publishers; 1989:1421–5.Google Scholar
- 13.Mózsik Gy, Jávor T. Therapy of ulcers with sulfhydryls and non-sulfhydryl antioxidants. In: Swabb EA, Szabó S, eds. Ulcer Disease: Investigation and Basis for Therapy. New York., Basel, Hong Kong: Marcel Dekkel Inc., 1991:321–41.Google Scholar
- 14.Mózsik Gy, Emerit I, Fehér J, Matkovics B, Vincze A, eds. Oxygen Free Radicals and Scavengers in the Natural Sciences. Budapest: Akadámiai Kiadó; 1993.Google Scholar
- 20.Mózsik Gy. Some feedback mechanisms by drugs in the interrelationships between the active transport system and adenylate system localized in the cell membrane. Eur J Pharmacol. 1969;7:318–27.Google Scholar
- 22.Mózsik Gy, Király Á, Sütő, G, Vincze Á. ATP breakdown and resynthesis in the development of gastrointestinal mucosal damage and its prevention in animals and human An overview of 25 years ulcer research studies. In: Mózsik Gy, Pár A, Csomós G et al., eds. Cell Injury and Protection in the Gastrointestinal Tract: From Basic Sciences to Clinical Perspectives. Budapest: Akademiai Kiadó; 1993:39–80.Google Scholar
- 24.Vincze Á, Garamszegi M, Jávor T, Sütő G., Mózsik Gy. The prevention of increased vascular permeability is not involved in gastric cytoprotective effect of β-carotene. Dig Dis Sci. 1990;35:1033–7.Google Scholar
- 25.Mózsik Gy, Bódis B, Garamszegi M et al. Role of the vagal nerve in the development of gastric mucosal injury and its prevention by atropine, cimetidine, β-carotene and prostacyclin in rats In: Szabó, S., Taché Y, eds. Neuroendocrinology of Gastrointestinal Ulceration. New York: Plenum Press; 1995:175–90.Google Scholar