Modulation of prostaglandin metabolism by K-MAP and prevention of toxic effect of cyclosporin on pancreatic islet cells.
The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.
Teraoka
S
S
Department of Surgery, Tokyo Women's Medical College, Japan.
Kawai
T
T
Babazono
T
T
Fuchinoue
S
S
Honda
H
H
Nakajima
I
I
Fujikawa
H
H
Hayashi
T
T
Nakagawa
Y
Y
Fujita
S
S
D010129:4-Aminobenzoic Acid / Q000494:pharmacology*; D062365:Aminobenzoates / Q000494:pharmacology*; D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D004347:Drug Interactions; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives* / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000652:urine; D015430:Weight Gain / Q000187:drug effects; D062366:para-Aminobenzoates
D062365:Aminobenzoates; D003524:Cyclosporins; D011453:Prostaglandins; D062366:para-Aminobenzoates; D013929:Thromboxane B2; C055108:4-aminobenzoic acid-N-mannoside; D008358:Mannose; D010129:4-Aminobenzoic Acid