Chronic Effects of Corticosteroid Oral Treatment in Rats on Blood Glucose and Serum Insulin Levels,Pancreatic Islet Morphology,and Immunostaining Characteristics

Abstract

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 hematoxylinand-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.

Keywords

Glucocorticoid electron microscopy morphometry

References

Burns J. (1975). Background staining and sensitivity of the unlabelled antibody-enzyme (PAP) method. Comparison with the peroxidase labelled antibody sandwich method using formalin fixed paraffin embedded material. Histochemistry 43: 291.

Filippono P. and Blass A. (1987). Deflazacort: A new glucocorticoid . Drugs of Today 23: 329-334.

Greenberger NJ , Toskes PP and Isselbacher KJ (1987). Diseases of the pancreas. In: Principles of Internal Medicine, 11th ed., E Braunwald , KJ Isselbacher , RG Petersdorf , JD Wilson , JB Martin , and AS Fauci (eds). McGraw-Hill, New York, pp. 1372-1384.

Hayashi Y. , Furukawa H. , and Hasegawa T. (1972). Pancreatic tumors in rats induced by 4-nitroquinoline-1-oxide derivatives. In: Topics in Chemical Carcinogenesis, W Nakahara , S. Takayama , T Sugimura and S Odashima (eds). University Park Press, Baltimore, MD, p. 53.

Mantel N. and Haenszel W. (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst. 22: 719-748.

Morohoshi T. , Kanda M. , and Klöppel G. (1984). On the histogenesis of experimental pancreatic endocrine tumors. Acta Pathol. Jpn . 34(2): 271-281.

Quade D. (1982). Nonparametric analysis of covariance by matching . Biometrics 38: 597-611.

Reaven EP and Reaven GM (1981). Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction. J. Clin. Invest. 68: 75-84.

Rosen VJ , Castanera TJ , Jones DC , and Kimeldorf DJ (1961). Islet-cell tumors of the pancreas in the irradiated and nonirradiated rat. Lab. Invest. 10: 608-616.

10.

Spencer AJ , Andreu M. , and Greaves P. (1986). Neoplasia and hyperplasia of pancreatic endocrine tissue in the rat: An immunocytochemical study. Vet. Pathol . 23: 11-15.

11.

Tukey JW , Ciminera JL , and Heyse JF (1985). Testing the statistical certainty of a response to increasing doses of a drug. Biometrics 41: 295-301.

12.

Wajchenberg BL , Prestes CF , Okada H. , Torres de Toledo e Souza I. , Lerario AC , Borghi VC , Malerbi DA , Giurna Filho A. , Liberman B. , and Gianella D. (1984). Glucocorticoids, glucose metabolism and hypothalamic-pituitary-adrenal axis . Adv. Exp. Med. BioL 171: 25-44.