Cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats.

Abstract

The effect of a high-cholesterol (CHOL) diet and corticosteroids on the toxicity of vitamin D2 (VD2) in rats was studied. VD2 was administered orally at the dosage of 5-60 x 10(4) IU/kg, once daily for 4 days. Animals fed CHOL showed a decrease in mortality due to VD2 treatment. Dietary CHOL inhibited toxic responses such as a diminished growth rate following anorexia, elevated serum calcium level and calcium deposition in tissues, which were produced by a sublethal dose of VD2 (20 x 10(4) IU/kg, once daily for 4 days). Animals pretreated with the high-CHOL diet from 2 weeks before the first VD2 administration showed much more symptomatic relief than those given this diet after the first VD2 administration. On the other hand, dexamethasone (DEX) as well as corticosterone remarkably increased the mortality due to VD2. The degree of VD2 toxicity, enhanced by DEX, was correlated with the degree of hypercalcemia and tissue calcification. Therefore, the inhibitory effect of CHOL is not likely to be due to activation of the CHOL-corticosterone system in the adrenal gland.