Protective effects of the chalcone 1-(4-hydroxy-phenyl)-3-m-tolyl-propenone against indomethacin-induced gastric erosive damage in rats

BACKGROUND: Non-steroidal anti-inflammatory drugs can result in peptic ulcer disease (PUD), a common condition worldwide. The aim of this study was to evaluate the anti-ulcer properties of the chalcone 1-(4-hydroxy-phenyl)-3-m-tolyl-propenone (HPTP) in rats using indomethacin as an ulcerogenic agent. Selected rats were divided into five groups; rats in the normal control and ulcerated groups received carboxyl methyl cellulose (CMC), those in the positive control group received omeprazole (20 mg/kg), while those in the two experimental groups received 50 mg/kg and 100 mg/kg HPTP, respectively. After 30 min, CMC was orally administered to animals in the normal group and 100 mg/kg indomethacin was orally administered to animals in the positive control, ulcerogenic control, and experimental groups. Six hours later, all animals were sacrificed. Ulcer area, acidity, gastric wall mucus, inhibition of erosive gastric damage, glutathione peroxidase (GPx), superoxide dismutase (SOD), prostaglandin E₂(PGE₂), and lipid peroxidation (MDA) of gastric homogenate were assessed. Hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) stains were used to study the histology and glycoproteins of the gastric mucosa, and expression of Bax and HSP70 proteins and TGF-β in the gastric wall was assessed using immunohistochemistry. RESULTS: None of the rats showed symptoms of kidney or liver toxicity during the study. Administration of HPTP decreased gastric acidity, increased gastric wall mucus and flattening of the gastric mucosa, and reduced the area of erosive gastric damage. HPTP treatment also dose-dependently increased SOD and GPx activity and PGE₂levels and decreased MDA. Furthermore, H&E staining showed decreased infiltration of leukocytes with edema of the submucosal layer. PAS staining showed intense uptake of magenta in gastric wall mucus of rats fed HPTP, and immunohistochemical staining of gastric mucosa revealed over-expression of HSP70 protein, down-regulation of Bax protein, and over-expression of TGF-β in rats administered HPTP. CONCLUSIONS: The chalcone HPTP can serve as a safe and effective anti-ulcer agent. It has been shown to increase pH and gastric wall mucus, increase GPx, SOD, and PGE₂levels, and decrease MDA levels. Ultimately, it also contributes towards over-expression of HSP protein and TGF-β, and down-regulation of Bax protein.