Premium
Effects of new antiinflammatory steroids derived from prednisolone on pituitary‐adrenal axis and lysosomal stabilization
Author(s) -
Heiman Ann S.,
Nathoo Zulfikarali M.,
Lee Henry J.
Publication year - 1982
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430020406
Subject(s) - corticosterone , prednisolone , endocrinology , medicine , chemistry , steroid , corticosteroid , biochemistry , biology , hormone
The pituitary‐adrenal axis suppression and lysosomal membrane stabilization of methyl steroid‐21‐oates, synthesized by modifying the 17β‐ketol side chain of prednisolone, were investigated by measuring plasma corticosterone and by determining abilities of the drugs to decrease extrusion of three liver lysosomal marker enzymes (acid phosphatase, beta‐glucuronidase, and aryl sulfatase) during incubation in severely hypo‐osmotic buffer. Animals were injected with 10 mg/kg drug suspensions i.m. at 20 hr and 2.5 hr prior to sacrifice. The parent compound prednisolone significantly suppressed pituitary adrenal function indicated by decreased plasma corticosterone levels. In contrast, the derivatives did not alter plasma corticosterone levels. When compared to controls, prednisolone, methyl 20‐dihydroprednisolonate, 1‐dehydro‐11β‐hydroxyandrostenedione, and to a lesser extent methyl prednisolonate retained significant lysosomal stabilization capacities, indicative of antiinflammatory activity. These data suggest that the new ester derivatives of prednisolone retained beneficial antiinflammatory activity but were devoid of significant adverse effects upon the pituitary‐adrenal axis.