griseofulvin and Liver-Diseases--Alcoholic

Intracytoplasmic eosinophilic inclusion bodies light-microscopically identical to human alcoholic hyalin were produced in hepatocytes of griseofulvin-treated mice. Electron-microscopic investigation on these inclusion bodies revealed two morphologically different fibrils. The most frequently observed fibrils in liver tissues appeared straight or slightly curved in longitudinal sections and granular in cross sections. High-power electron micrographs on these fibrils revealed that each fibril consisted of parallel-running fine filaments of about 1.25 nm thick which were separated by spaces of about 1.25 nm. The ultrastructural appearance of these fibrils resembled that of myelin sheath in longitudinal sections. They usually measured from 13 to 32 nm wide and up to 0.9 micron long. Fibrils with larger diameter of up to 62 nm were infrequently encountered. Rod-like fibrils ultrastructurally similar to those seen in human alcoholic hyalin were also found in isolated materials. All these fibrils were isolated in the same fraction by a slight modification of a discontinuous sucrose gradient ultracentrifugation and a two phase polymer centrifugation. The present observation suggests that intracytoplasmic inclusion bodies produced in this animal model are composed of morphologically different fibrils. These different fibrils could share the same origin.

Topics: Animals; Female; Griseofulvin; Inclusion Bodies; Liver; Liver Diseases, Alcoholic; Mice; Mitochondria, Liver; Myelin Sheath

Rhodamine B staining in conjunction with fluorescence microscopy is shown to demonstrate Mallory bodies. Mallory body morphology, localization, and distribution in hepatocytes from griseofulvin-fed mice, human hepatoma, and human alcoholics were similar to those observed in the same tissues after conventional staining methods for Mallory bodies. The presence of these inclusions was further confirmed by specific cytochemical localization with indirect immunoperoxidase labeling, horseradish peroxidase labeling, and electron microscopy. Other tinctorial or histochemical procedures previously used for keratin or prekeratin (modified Mallory stain, Kreyberg method, Pauly method for histidine) also stained Mallory bodies for study with white light microscopy but with decreasing sensitivity respectively. Mallory bodies from mouse and human liver both appear to contain a keratin-like moiety. This entity may be simply, rapidly, and permanently stained with rhodamine B, and selectively and reproducibly demonstrated with fluorescence microscopy.

Topics: Animals; Carcinoma, Hepatocellular; Endoplasmic Reticulum; Griseofulvin; Humans; Keratins; Liver; Liver Diseases, Alcoholic; Liver Neoplasms; Mice; Microscopy, Fluorescence; Rhodamines; Staining and Labeling; Xanthenes