Glucocorticoid-induced apoptosis of thymocytes in rats

Apoptosis or cell suicide or programmed cell death (PCD) is an important mechanism in both development and homeostasis in adult tissues for the removal of either superfluous, infected, transformed or damaged cell by activation of an intrinsic suicide program. Signals may either suppress or promote apoptosis. Glucocorticoids are well-known signals promoting apoptosis in rat thymocytes. Dexamethasone, as a prototype of corticosteroids, may induce indigenous endonuclease-mediated cell apoptosis. Therefore we apply dexamethasone as a synthetic glucocorticoid in rats. The aim of the present study were to evaluate the effects of dexamethasone on rat cells, study light and electron microscopic changes and of course, demonstrate the relationship between doses of drug and extent of apoptosis.

We organized treatment group consisting of four sub-groups (each including 5 rats), naming T-a, T-b, T-c and T-d, each received dexamethasone intraperitoneally at the dosage of 0.5, 1.5, 2.5 and 3.5 mg/kg, respectively. Similarly, four control sub groups were assigned. Six hours after administration, the thymus gland of all treatment and control group rats were ectomized and investigated by light and electronic microscopes.

Apoptotic bodies appeared as round or oval cytoplasmic masses with or without contained basophilic nuclear material and well defined cresentric clamps of chromatin in light microscope, weheras, electronic microscope studies demonstrated the peripheral nuclear chromatin form aggregate of osmiophilic granules, which separated from the fibrillar core and irregular cell outline nuclear fragments and whirling endoplasmic reticulum. There was a positive association between drug dosage and severity of apoptosis.

Results have revealed that corticosteroids in therapeutic and over-dose excite and stimulate DNA fragmentation in thymocytes. Corticosteroid-induced death of thymocytes is recognized as a calcium dependent process.