Protective effect of tauroursodeoxycholate against chenodeoxycholate-induced damage to cultured rabbit gastric cells.
Ursodeoxycholate (UDC) and tauroursodeoxycholate (TUDC) have been reported to be protective against liver injury induced by other bile salts. UDC also has been shown to be effective against refluxed bile-induced gastritis after gastric surgery. However the mechanism of the therapeutic effect of UDC on gastric mucosa has not been known. In the present study, cytoprotective actions of UDC and TUDC against chenodeoxycholate (CDC)-induced gastric injury were investigated using rabbit gastric cell cultures without systemic factors. Rabbit gastric mucosal cells were cultured after the isolation of rabbit gastric cells with collagenase and ethylenediaminetetraacetic acid. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells and MTT assay. Prostaglandin (PG) E2 was assayed by radioimmunoassay. Concentrations of CDC greater than 0.5 mM or UDC greater than 5 mM caused cellular damage and increased 51Cr release in a dose-dependent and time-dependent fashion, while TUDC up to 10 mM did not. TUDC, but not UDC, showed a significant decrease of CDC (1.5 mM)-induced 51Cr release dose dependently. The protective effect of TUDC against CDC-induced damage was confirmed by MTT assay. On phase-contrast microscopy, disruption of monolayers induced by CDC (1.5 mM) was clearly protected by TUDC (10 mM). Free radical scavengers (500 units/ml of superoxide dismutase, 300 units/ml of catalase, and 100 mM of dimethyl sulfoxide) or a calcium blocker (10(-7)-10(-5) M verapamil) did not show significant protection against CDC-induced damage. Deprivation of Ca2+ in the media did not affect CDC-induced damage. Thus free radicals or Ca2+ might not be involved in the cell toxicity of CDC.(ABSTRACT TRUNCATED AT 250 WORDS)
Ota
S
S
Second Department of Internal Medicine, University of Tokyo, Japan.
Tsukahara
H
H
Terano
A
A
Hata
Y
Y
Hiraishi
H
H
Mutoh
H
H
Sugimoto
T
T
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007536:Isomerism; D008297:Male; D011817:Rabbits; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D001647:Bile Acids and Salts; D005609:Free Radicals; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014700:Verapamil; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin