Chlorcyclizine-induced changes in the epididymides and the prostatic complex of rats.

Abstract

In a previous study, we reported that chlorcyclizine, an antihistaminic and hypocholesterohemic agent, was capable of producing severe damage to the germinal epithelium and the Leydig cells in the testes of rats when administered in the diet at the level of 0.18%. The injuries to the germinal epithelium were essentially irreversible, while those involving the Leydig cells were reversible on withdrawal of the chlorcyclizine diet. In this report, the changes produced by the same drug in the epididymides and the prostatic complex (comprising the prostate proper, seminal vesicles, and coagulating glands) were described. Two types of changes were observed: 1) those secondary to the androgen deficiency accompanying Leydig cell damage and 2) those due to a direct cytotoxic effect of the chlorcyclizine. The changes secondary to androgen deficiency as a result of Leydig cell damage consisted mainly of an atrophy of the lining epithelium of the prostate proper, particularly its ventral lobe, which is one of the most sensitive biological indicators of androgen levels. The observation of similar but more severe atrophy in the prostate of castrated animals, and the ability of testosterone to abolish the chlorcyclizine-induced atrophy, were in support of androgen deficiency as its underlying cause. The direct cytotoxic effect consisted of a peculiar cytoplasmic vacuolation of the lining epithelium of the epididymides, seminal vesicles, and to a lesser extent the coagulating glands. Ultrastructural examination of the epididymal epithelium disclosed that the cytoplasmic vacuoles seen on light microscopy were filled with large masses of multicentric myeloid bodies. That these vacuolations were mainly due to a direct cytotoxic effect of chlorcyclizine was supported by the following observations: the changes were not seen in castrated animals; they were not preventable by concurrent testosterone injections and were only reversible by withdrawing the chlorcyclizine in the diet.