Effect of cyclosporine A at therapeutic and toxic doses on the superluteinized ovaries in BALB/c mice.

Administration of cyclosporine (CyA) at therapeutic (10 to 50 mg/kg per day) and at toxic doses (100 mg/kg per day) to gonadotropin-treated immature BALB/c mice led to detection of this drug in the blood and in the ovary at levels that were dose- and time-dependent, the maximum level reached in the blood was 23.8 micrograms/mL, and in the ovary was 0.164 micrograms/mg ovarian weight. Although these were toxic levels, there was no adverse effect on the survival rate as it ranged from 90% to 100%, nor did it induce body weight reduction. In addition, it did not cause any significant structural alterations in the ovarian tissues. The histology of the graafian follicles and the corpora lutea were the same as in the control. On the other hand, the numbers of the corpora lutea were decreased in the ovaries of the CyA-treated mice. This was parallel to the reported decrease in plasma progesterone level to values less than that of the control. These results indicate that the use of gonadotropin primed mice decreased the degree of CyA-induced toxicity.