Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity.
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.
Löhr
M
M
Institute of Pathology, University of Hamburg, Federal Republic of Germany.
Müller
M K
MK
Goebell
H
H
Klöppel
G
G
D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011458:Prostaglandins E / Q000627:therapeutic use*; D011465:Prostaglandins, Synthetic; D051381:Rats; D011919:Rats, Inbred Strains; D016630:Rioprostil
D003524:Cyclosporins; D007328:Insulin; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D016630:Rioprostil