Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity |
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Authors: | M Löhr M K Müller H Goebell G Klöppel |
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Institution: | (1) Institute of Pathology, University of Hamburg, Hamburg, (Federal Republic of Germany);(2) Division of Gastroenterology, Department of Medicine, University of Essen, Essen, (Federal Republic of Germany);(3) Institute of Pathology, Free University of Brussels, Brussels, (Belgium);(4) Present address: Scripps Clinic and Research Foundation, IMM 6, 10666 N Torrey Pines Road, 92037 La Jolla, CA, USA |
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Abstract: | Summary Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation. |
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Keywords: | Cytoprotection cyclosporin endocrine pancreas insulin-secretion electron microscopy prostaglandin analogue rioprostil |
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