Cytoprotective effect of acetaminophen against taurocholate-induced damage to rat gastric monolayer cultures.
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 PGE2 and 6-keto-prostaglandin F1a (6KF) was also studied. Sodium taurocholate caused cell death in a dose-dependent manner as indicated by increased 51Cr release. Preincubation with 5 mM acetaminophen significantly reduced 51Cr release caused by 5 mM sodium taurocholate, producing a 40% increase in cell survival. This cytoprotection was not blocked by indomethacin. PGE2 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 vitro independent of indirect factors such as blood flow and (2) this protection is not associated with increased prostaglandin production.
Ota
S
S
Department of Medicine, Long Beach Veterans Administration Medical Center, California 90822.
Razandi
M
M
Sekhon
S
S
Terano
A
A
Hiraishi
H
H
Ivey
K J
KJ
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008858:Microscopy, Phase-Contrast; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D011458:Prostaglandins E; D000082:Acetaminophen; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; D015232:Dinoprostone; D007213:Indomethacin