Cytoprotective effect of acetaminophen against taurocholate-induced damage to rat gastric monolayer cultures

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Abstract
Acetaminophen has recently been reported to protect against drug damage to gastric mucosa in vivo.The present study tested acetaminophen protection in cultured rat gastric mucous cells against sodium taurocholate-induced damage and assessed the role of endogenous prostaglandins. Cell damage was assessed by phase-contrast microscopy and quantitated by Chromium-51 release assay which positively correlated with the trypan blue dye exclusion test (r=0.98). The effect of acetaminophen on the production of PGE 2 and 6-keto-prostaglandin F 1a (6KF) was also studied. Sodium taurocholate caused cell death in a dose-dependent manner as indicated by increased 51 Cr release. Preincubation with 5 mM acetaminophen significantly reduced 51 Cr release caused by 5 mM sodium taurocholate, producing a 40% increase in cell survival. This cytoprotection was not blocked by indomethacin. PGE 2 and 6KF of the media did not change after preincubation with nondamaging concentrations of acetaminophen or taurocholate. These results indicate that: (1) acetaminophen exerts a direct protective effect on gastric mucous cells cultured in vitroindependent of indirect factors such as blood flow and (2) this protection is not associated with increased prostaglandin production.