Ultrastructure of acute adrenocortical damage due to aminoglutethimide (Elipten® Ciba) in rats

Abstract

Adult female albino rats given daily peroral doses of 50 mg aminoglutethimide (Elipten® Ciba) developed in short-term experiments an increase in size and number of liposomes within adrenocortical cells (ACC) as well as other conspicuous focal changes. The cytoplasm of some ACC showed a marked increase in transparency due to the presence of optically empty membrane-bound vacuoles and spaces closely related to liposomes and the smooth endoplasmic reticulum. Advanced changes were associated with mitochondrial swelling, an increase in translucency of the cytoplasmic matrix and chromatin clumping. They resulted in gradual karyo- and cytolysis associated with fragmentation of the nuclear and cellular membranes. Cavitation and lipoid transformation of the mitochondria was observed in the remaining ACC from day 3. At day 1 the disappearing ACC were surrounded by numerous polymorphonuclear leucocytes which also invaded the ACC proper. Simultaneously there also occurred a moderate number of mononuclear cells predominantly derived from the blood monocytes. At day 3 the monocytes and histiocytes prevailed markedly and assumed the characteristics of lipophages. Severe haemodynamic changes that occurred at day 1 were associated with the developement of hyaline droplets and protein “lakes”. The alterations described show that an apparently pure resorptive macrophagic reaction evoked by distintegration of ACC may assume the character of an alterative-exudative inflammation with a prevalence of polymorphonuclears and blood monocytes in the inflammatory exudate during the early stages of the condition. The focal changes as observed during day 1 of the experiment forced us to consider the possibility of a direct injury to some essential intracellular enzyme systems by aminoglutethimide under the present experimental conditions.