Protection by nitecapone against sodium taurocholate-induced damage to cultured gastric cells |
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Authors: | Yahong Tu MD Sirpa Ranta MSc Erkki Nissinen PhD Dr Inge-Britt Lindén PhD |
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Institution: | (1) Orion-Farmos Pharmaceuticals, Orion Research Center, P.O. Box 65, SF-02101 Espoo, Finland |
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Abstract: | The goal of this study was to observe if nitecapone protected against taurocholate-induced damage in primary cultured rat gastric mucosal cells, as well as in a well-differentiated human gastric epithelial cell line (MKN 28). Prostaglandins were measured to analyze the protection mechanism. In primary rat gastric mucosal cell culture, nitecapone 125–250 M protected the cells significantly against damage induced by sodidum taurocholate, increasing cell viability by 31–38%. In the human gastric epithelial cell line, in which mitochondrial activity was measured as an indication of cell viability, nitecapone (62.5–250 M) protected the cells against sodium taurocholate-induced damage by 12–20%. Prostaglandin E2, thromboxane B2, and 6-keto-prostaglandin F1 measurements in the primary cultured rat gastric mucosal cells showed that nitecapone (125 M and 250 M) significantly stimulated prostaglandin E2 production (84.7% and 61.0%, respectively), and inhibited thromboxane B2 formation (50% at 250 M), while the 6-keto-prostaglandin F1 formation was unaffected. Nitecapone had no effect on prostaglandin E2 production in the MKN 28 epithelial cell line. Indomethacin or aspirin, at concentrations that did not affect cell viability, antagonized the stimulative effect of nitecapone on prostaglandin E2 formation in the primary cultured rat gastric mucosal cells. Although the prostaglandin E2 synthesis was blocked, nitecapone still protected against cell damage induced by taurocholate. These results demonstrated the direct and efficacious protection of nitecapone on gastric cell level and suggest that the cytoprotection by nitecapone against taurocholate may not be mediated through the mechanism of stimulated synthesis of prostaglandin E2. |
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Keywords: | nitecapone sodium taurocholate prostaglandins gastric mucosal cells human gastric epithelial cell line cytoprotection |
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