Aims: The aims of these studies were to evaluate the biochemical mechanisms involving energy metabolism of: 1. 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); 2. 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. Methods: 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. Results: The results showed that: 1. The mucosal damage (number and severity) reached about 50% of that obtained 60 min after administration of the necrotizing agents in both models; 2. 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; 3. 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; 4. ATP-cAMP transformation was increased in the early period by PGI2 and in the late phase by β-carotene; 5. No significant change was obtained in the 'energy charge' and lactate by PGI2 or β-carotene administration; 6. 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 afteradministration of EtOH and HCl. Conclusions: 1. The development of gastric mucosal damage and its prevention can be discriminated into early and late phases; 2. The early phase of gastric mucosal damage can be prevented by PGI2, and the late phase by β-carotene; 3. The β-carotene effect only partly depends on its presumptive scavenging properties; and 4. PGI2 prevents the development of gastric mucosal damage, while β-carotene stimulates the repair mechanisms. 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.
- acid-dependent gastric ulcer
- cellular energy systems
- early and late phase of gastric mucosal damage
- non-acid-dependent gastric ulcer
- repair mechanisms
ASJC Scopus subject areas
- Pharmacology (medical)