Light and electron microscopy of hepatocellular changes in griseofulvin fed mice. Particular reference to Mallory bodies

Male Swiss Webster mice were fed a diet containing 2.5 percent griseofulvin (GF). Serially progressive light and electron microscopic hepatic altertions were present from one day on and grossly visible hepatomegaly from two weeks until termination at 22 weeks. GF induced liver changes included hepatocyte nuclear and cytoplasmic hypertrophy, increased incidence of necrosis and mitosis, Kupffer cell activation, bile duct proliferation and portal fibrosis. Protoporphyrin crystals were present in hepatocyte cytoplasm as early as one day after GF feeding. Hepatocellular hyalin was initially noted at seven weeks. Thereafter, the hyalin increased in prominence and frequency of occurrence. Ultrastructurally, three types of hyalin have been presently demonstrated to correspond to Mallory bodies (MB) reported in human liver disease. Forms intermediate in appearance between various MB types suggested transition from one to another. Areas of organelle free cytosol with abundant, loosely scattered filamentous elements as well as vesicular, smooth surfaced endoplasmic reticulum and ribosomes appeared preceding and closely associated with MB formation. Similarities of hepatocellular MB observed in GF fed mice and reported earlier in human alcoholic liver disease suggest a common pathway in its formation as a response to divergent noxious insults.