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Evaluation of antiulcer agents with a human adenocarcinoma cell line (AGS)

Authors
Journal
International Journal of Pharmaceutics
0378-5173
Publisher
Elsevier
Publication Date
Volume
129
Identifiers
DOI: 10.1016/0378-5173(95)04271-7
Keywords
  • Gastric Epithelium
  • Ags Cell Line
  • Cell Culture
  • Cytoprotection
  • Sucralfate

Abstract

Abstract A human gastric carcinoma epithelial cell line (AGS) was studied as an alternative in vitro model for evaluating the cytoprotective effects of antiulcer agents. Cytoprotection was measured by cleavage of 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) by surviving AGS cells following exposure to selected antiulcer agents and/or pH 3 medium, indomethacin, or ethanol. Sucralfate in three different preparations (including a sucralfate suspension, acid-solubilized sucralfate and sucralfate-xg, a sucralfate suspension formulated with xanthine gum) at concentrations of 2 and 5 mg/ml provided significant protection (40–99% of untreated control) against pH 3 medium-induced damage. Sucralfate-xg at 5 mg/ml almost completely blocked the toxic effect of 10 mM indomethacin. The survival of cells after indomethacin exposure was about 70 and 80% of untreated controls when the cells were pretreated with 5 mg/ml of either sucralfate or acid-solubilized sucralfate. Acid-solubilized sucralfate proved to be an effective protection against a 13% ethanol insult; about four times greater than the effect of a simple sucralfate suspension against the ethanol insult. Potassium sucrose octasulfate (KSOS) or aluminum hydroxide individually presented either partial or little protection against acid, indomethacin, or ethanol insults. However, a mixture of KSOS and aluminum hydroxide enhanced the AGS cells recovery from a pretreatment with acidified medium. Although not effective as a cytoprotective agent, 0.02–5 mg/ml KSOS stimulated AGS cell growth up to 40% over untreated controls. Overall results correlated well, qualitatively, with previous studies with primary cultures of rat gastric epithelial cells and rat and human studies, suggesting that the AGS cell line may also serve as a suitable model for preliminary evaluation of some antiulcer agents.

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