Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats.

Abstract	The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles.
Authors	T Hirano, T Manabe, H Printz, T Tobe
Journal	Surgery, gynecology & obstetrics (Surg Gynecol Obstet) Vol. 175 Issue 6 Pg. 495-500 (Dec 1992) ISSN: 0039-6087 [Print] United States
PMID	1280373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Esters Guanidines Trypsin Inhibitors camostat Gabexate Cyclosporine Amylases Cathepsin B
Topics	Amylases (blood, chemistry) Animals Cathepsin B (chemistry) Cyclosporine (administration & dosage, adverse effects) Drug Evaluation, Preclinical Edema (chemically induced, pathology) Esters Gabexate (analogs & derivatives) Guanidines (administration & dosage, pharmacology) Injections, Subcutaneous Lysosomes (drug effects, enzymology) Male Pancreas (chemistry, drug effects, pathology) Pancreatic Juice (drug effects, enzymology) Rats Rats, Wistar Transplantation Immunology Trypsin Inhibitors (administration & dosage, pharmacology)

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