Chronic effects of corticosteroid oral treatment in rats on blood glucose and serum insulin levels, pancreatic islet morphology, and immunostaining characteristics.
Corticosteroids have for many years proven beneficial in the necessary treatment of diseases and conditions that respond to their anti-inflammatory, immunosuppressive, or hormonal effects. Deflazacort is a derivative of prednisolone and is currently used in humans. Deflazacort was fed in the diet for 1 yr to Crl:CD BR rats at doses from 0.03 to 1.0 mg/kg/day to evaluate its toxic potential. Deflazacort-induced pancreatic islet cell hyperplasia in the 1-yr study was evaluated using subjective and objective methods on routine hematoxylin-and-eosin- or peroxidase-anti-peroxidase-stained preparations of pancreas (islets); the relationship of blood glucose and serum insulin levels to doses of deflazacort administered to rats was also examined. Diagnostic electron microscopy was conducted on similar proliferative islet lesions for a few high-dose males of a parallel carcinogenicity study. This study revealed that proliferative islet lesions were comprised mainly of beta cells (insulin producing) and that the islet area correlated well with hyperplasia grade and dose. However, there were no statistically significant relationships among reductions in blood glucose, serum insulin concentration, and proliferative islet alterations.
Zwicker
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Marion Merrell Dow, Inc., Indianapolis, Indiana 46268-0470.
Eyster
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000633:toxicity*; D001786:Blood Glucose / Q000187:drug effects*; D005260:Female; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007328:Insulin; D011282:Pregnenediones; C021988:deflazacort