title: Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice.
abstract: The gastroprotective activity of the new semi-synthetic solidagenone derivative 15,16-epoxy8(9),13(16),14-labdatrien-7 beta-methoxy-6 beta-ol (ELMO) has been assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of action. The effect of ELMO on the prostaglandin E2 content, cellular reduced glutathione (GSH) and protection against damage induced by sodium taurocholate was assessed against AGS cells. The effect of ELMO on the growth of AGS and fibroblast cultures was evaluated. The superoxide anion scavenging capacity of the compound was studied also. The cytotoxicity of ELMO, expressed as cell viability, was assessed using two independent endpoints: neutral red uptake (NRU) and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells. A single oral dose of ELMO (10 and 20 mg kg(-1)) inhibited the appearance of gastric lesions in mice displaying similar values to lansoprazole at 20 mg kg(-1). At 40 microM ELMO increased the prostaglandin E2 content but not GSH in AGS cells. The compound showed no effect on sodium taurocholate-induced damage and was devoid of superoxide anion scavenging activity. Concentrations of 0.5, 1, 2 and 4 microM stimulated fibroblast but not AGS cell proliferation. The compound showed weak cytotoxicity with values (IC50) of 411 (NRU) and 418 microM (MTT) for fibroblasts and 261 microM (NRU) for AGS cells. The results support further pharmacological study of this compound as a potential new anti-ulcerogenic drug.
authors.affiliation: Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile. jrodrig@utalca.cl
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Rodríguez
authors.forename: Cristina
authors.initials: C
authors.lastname: Theoduloz
authors.forename: Marianela
authors.initials: M
authors.lastname: Sánchez
authors.forename: Tania
authors.initials: T
authors.lastname: Yáñez
authors.forename: Iván
authors.initials: I
authors.lastname: Razmilic
authors.forename: Guillermo
authors.initials: G
authors.lastname: Schmeda-Hirschmann
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002677:Chile; D015232:Dinoprostone / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004848:Epithelium / Q000473:pathology; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000009:adverse effects; D020128:Inhibitory Concentration 50; D064747:Lansoprazole; D008168:Lung / Q000473:pathology; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D009499:Neutral Red / Q000737:chemistry; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013778:Tetrazolium Salts / Q000737:chemistry
chemical_list: C503605:15,16-epoxy8(9),13(16),14-labdatrien-7 beta-methoxy-6 beta-ol; D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D005663:Furans; D009281:Naphthalenes; D013778:Tetrazolium Salts; D064747:Lansoprazole; C406719:solidagenone; D009499:Neutral Red; D000431:Ethanol; D015232:Dinoprostone; D009853:Omeprazole; D006851:Hydrochloric Acid