AN ELECTRON-MICROSCOPIC STUDY OF APOPTOSIS INDUCED BY CYCLOHEXIMIDE IN RAT-LIVER

A histological and ultrastructural study, coupled with transmission an d scanning electron microscopy of the early changes in the liver follo wing a single administration of cycloheximide (CHX), was carried out i n male Wistar rats. At the histological level, apoptosis was already p resent in the liver 2 h after treatment. By scanning electron microsco py, the following sequential changes were observed: brightness and pro gressive detachment of hepatocytes from neighbouring cells, formation of surface infolds with multiple blebs and, finally, release of severa l membrane-bounded apoptotic bodies (ABs) in the extracellular space a nd into the sinusoidal lumen. Three hours after CHX administration, th e apoptotic cycle was completed, as shown by the presence of phagocyto sed ABs inside the cytoplasm of intact Liver cells. Light microscopic examination of the liver 6 h after CHX administration showed ABs mainl y located in the cytoplasm of intact hepatocytes and inside activated Kupffer cells. By transmission electron microscopy, it was possible to demonstrate that cells undergoing apoptosis were hepatocytes. At 24 h , the livers of treated animals appeared normal, with no evidence of a poptosis.