Ultrastructural changes in hepatocytes induced by pregnenolone-16a-carbonitrile (PCN)

Pretreatment with pregnenolone-16a-carbonitrile (PCN) protects the rat against the toxic effects of indomethacin, digitoxin, cyclophosphamide and many other injurious agents. In experiments in vivo Selye has recently shown that conditioning by higher PCN doses gives broader "protection spectra". In the present experiments, we studied the effect of different doses of PCN on the ultrastructure of the hepatocytes. PCN was administered to the groups of female rats at doses of 1.0, 0.1 and 0.03 mg, twice daily for three days respectively. Sixteen hours after the last dose, the specimens of liver tissue were fixed, dehydrated and embedded in Epon resin; the ultrathin sections selected from midzonal areas were negatively stained and studied under the electron microscope. We found that PCN produces morphological changes in rat hepatocytes mainly by smooth-surfaced endoplasmic reticulum (SER) proliferation and that the degree of ultrastructural alteration is dose dependent.