Effects of Dexamethasone on the Development of Radiation Nephropathy in the Rat

Abstract

Low-dose, chronic administration of the synthetic glucocorticoid, dexamethasone, to male CD-I rats in the drinking water or by osmotic minipumps implanted subcutaneously after supralethal irradiation of the kidneys (20 Gy) was studied. The effectiveness of treatment with dexamethasone in the drinking water at concentrations of 23 micrograms/l to 188 micrograms/l and treatment times varying from 33 to 166 days was evaluated. At monthly intervals kidney function was assayed by measuring the clearance of 51Cr-ethylenediaminetetraacetic acid. All dexamethasone treatment regimens increased survival times significantly and delayed the development of kidney dysfunction. The most effective combination of concentration of dexamethasone in drinking water and treatment interval after irradiation with respect to survival was 94 micrograms/l and 88 days. However, a slightly longer survival and a better functional result was obtained if an equivalent amount of dexamethasone was administered by minipumps. Shielding the adrenal glands during kidney irradiation did not prolong survival. This shows that the beneficial effect of dexamethasone is not due to compensation for reduced adrenal glucocorticoid production resulting from concomitant exposures of these glands during kidney irradiation.