ISSN:
1573-2568
Keywords:
cultured rabbit gastric cells
;
cytoprotection
;
tauroursodeoxycholate
;
ursodeoxycholate
;
chenodeoxycholate
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 measuring51Cr release from prelabeled cells and MTT assay. Prostaglandin (PG) E2 was assayed by radioimmunoassay. Concentrations of CDC〉0.5mM or UDC〉5mM caused cellular damage and increased51Cr 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)-induced51Cr 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 of Ca2+ might not be involved in the cell toxicity of CDC. Although TUDC (10 mM) significantly increased PGE2 production by cultured cells, indomethacin (10−4 M) did not reduce protective effects of TUDC, as assessed by51Cr release and MTT assay. In conclusion TUDC is cytoprotective against CDC-induced damage to cultured rabbit gastric cells. Neither free radicals, Ca2+, nor endogenous PGs may play leading roles in the mechanism of this action.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01298867
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