Gastroprotective Effect of Nicorandil in Indomethacin and Alcohol-Induced Acute Ulcers

• Published in: Applied biochemistry and biotechnology 2009-03, Vol.152 (3), p.449-459
• Main Authors: El-Moselhy, M. A, Abdel-Hamid, N. M, Abdel-Raheim, S. R
• Format: Article
• Language: English
• Subjects: Acute Disease; Alcohols; Animals; Anti-inflammatory agents; Biochemistry; Biological and medical sciences; Biomedical research; Biotechnology; Chemistry; Chemistry and Materials Science; Ethanol; Fundamental and applied biological sciences. Psychology; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastrointestinal diseases; Histology; Indomethacin; Infiltration; Male; Medical treatment; Nicorandil - pharmacology; Nicorandil - therapeutic use; Nitric oxide; Nitric Oxide - metabolism; Nitrogen oxides; Nonsteroidal anti-inflammatory drugs; Oxidative stress; Peroxidation; Pharmacology; Photochemicals; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rats; Rats, Wistar; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Thiobarbituric Acid Reactive Substances - metabolism; Tissues; Tumor Necrosis Factor-alpha - blood; Ulcers
• ISSN: 0273-2289; 1559-0291
• DOI: 10.1007/s12010-008-8384-z

Despite the fact that dietary habits and lifestyles are incredibly advancing, gastric ulceration is still a terrible complaint. Extensive use of non-steroidal anti-inflammatory drugs (NSAIDs) and alcohol, in addition to stress, are all predisposing factors for ulcers. Most medical treatments are always time consuming and not efficient or satisfactory to the patients. Cardiovascular patients always need NSAIDs, or mostly cannot quit alcohols, while using many cardiovascular drugs. We aim to study a possible benefit of a common nitrogen oxide donor, anti-anginal drug, nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate ester], in managing acute gastric ulcers through studying its effect on some relevant intermediates to ulcerogenesis as lipid peroxidation, tumor necrosis factor-alpha (TNF-α), and nitric oxide (NO). In addition, gastric mucosal histology was studied to pursue the drug effects on tissue level. Our study revealed that both indomethacin and alcohol induced gastric ulcer mainly through up-regulation of gastric mucosal lipid peroxidation, local tissue inflammation, leukocytic infiltration, and necrosis. Both ulcerogens significantly elevated TNF-α and decreased NO, initiating ulcer formation. Nicorandil pretreatment depicted a higher preventive index in indomethacin- (89.8%) and alcohol-induced (77.7%) acute ulceration. On the tissue level, it also protected the gastric mucosa combating leukocyte infiltration and tissue congestion. Nicorandil protected tissue necrosis through decreasing oxidative stress, elevating NO levels, and down-regulating the ulcerogen-induced TNF-α elevation and improved sub-mucosal blood supply. We conclude that nicorandil may be a suitable bimodal treatment for cardiovascular patients who are at high risk of gastric ulcers by using variable analgesics to alleviate possible cardiac pain episodes, and probably frequent doses will offer a more established and long-lasting protection.