title: Gastroprotective activity and mechanism of novel dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration.
abstract: Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P<0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P<0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-α and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia. salgamohd@yahoo.com
authors.forename: Muhammad Saleh
authors.initials: MS
authors.lastname: Salga
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D023382:Toxicity Tests, Acute; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; C570631:dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate; D016753:Interleukin-10; D000077489:Piperazine; D000431:Ethanol; D015032:Zinc