Fate of Mallory Body–Containing Hepatocytes: Disappearance of Mallory Bodies and Restoration of the Hepatocytic Intermediate Filament Cytoskeleton After Drug Withdrawal in the Griseofulvin–Treated Mouse

Abstract

Mallory bodies are characteristic morphological features of alcoholic hepatitis in man and can be produced in the mouse by chronic griseofulvin intoxication. The appearance of Mallory bodies in hepatocytes is associated with derangement of the cytokeratin intermediate filament cytoskeleton, at least as revealed by immunofluorescence and suggested by immunoelectron microscopy. Immunohistochemical studies were performed to answer the question whether Mallory body formation and cytoskeleton alterations finally lead to cell death or are reversible phenomena. Chronically griseofulvin-intoxicated mice killed at different stages of recovery on a normal diet served as experimental animals. It could be shown that (a) Mallory bodies are very durable structures and are found for up to 6 mo after griseofulvin withdrawal as a result of persistence and neoformation; (b) new Mallory bodies can appear even several months after cessation of griseofulvin feeding; (c) Mallory body formation and cytoskeletal changes by themselves do not lead to irreversible cell damage; (d) the cytoskeletal changes are reversible within 7 mo after griseofulvin withdrawal; (e) a dissociation between disappearance of Mallory bodies and restoration of a regularly immunostained cytoplasmic cytokeratin meshwork is observed.