Primary culture of rat gastric epithelial cells as an in vitro model to evaluate antiulcer agents.
Primary rat gastric cell cultures were investigated as an in vitro model for evaluating antiulcer agents. Following exposure to concentrations of up to 5 mg/mL of an antiulcer agent sucralfate, an aluminum hydroxide complex of sucrose octasulfate, cultured cells were treated with either pH 3.5 medium or 3.5 mM indomethacin. Cytoprotection was evaluated by colony forming efficiency, neutral red uptake, and 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) hydrolysis. By each measure, and depending on damaging agent, 2 and 5 mg/mL sucralfate provided partial (50% of untreated control) to near-complete (90% of untreated control) cytoprotection, respectively. Aluminum hydroxide also provided partial (55% of untreated control) to near-complete (more than 90% of untreated control) cytoprotection at 2 and 5 mg/mL, respectively, for the pH 3.5 medium-induced damage. Over a concentration range of 0.05 to 5 mg/mL, the potassium salt of sucrose octasulfate, KSOS, stimulated cell growth up to 40-60% over untreated controls but had little or no cytoprotective action in the presence of either 3.5 mM indomethacin or pH 3.5 medium. Overall results suggested that sucralfate may have at least two roles in influencing gastric epithelial cell function, cytoprotection and stimulation of cell growth in vitro. These observations serve as a basis for further study of in vitro models in evaluating the cytoprotective activity of antiulcer agents and their respective mechanisms of action.
Zheng
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Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Shah
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PK
Audus
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KL
D000143:Acids / Q000633:toxicity; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004396:Coloring Agents; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells; D005753:Gastric Mucosa / Q000166:cytology*; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000633:toxicity; D008858:Microscopy, Phase-Contrast; D009499:Neutral Red; D051381:Rats; D017207:Rats, Sprague-Dawley; D013392:Sucralfate / Q000494:pharmacology; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000143:Acids; D000897:Anti-Ulcer Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D009499:Neutral Red; D013392:Sucralfate; D013395:Sucrose; D000536:Aluminum Hydroxide; C022616:thiazolyl blue; C053081:sucrose octasulfate; D007213:Indomethacin