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Updated: Aug 10, 2026
3D Imaging of the Liver Extracellular Matrix in a Mouse Model of Non-Alcoholic Steatohepatitis
Published on: February 25, 2022
Light and electron microscopy of hepatocellular changes in griseofulvin fed mice. Particular reference to Mallory
Abstract:
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.
Insights
Griseofulvin (GF) causes progressive liver damage in mice, including hepatomegaly and Mallory body formation. These findings suggest a common pathway for liver injury in response to different toxins.
Area of Science:
- Hepatology
- Toxicology
- Pathology
Background:
- Griseofulvin (GF) is an antifungal medication.
- Liver injury can result from various toxic insults.
- Mallory bodies (MB) are indicative of liver damage in humans.
Purpose of the Study:
- To investigate the hepatic effects of griseofulvin (GF) in a mouse model.
- To characterize the ultrastructural changes associated with GF-induced liver injury.
- To compare GF-induced hepatocellular changes with human liver diseases.
Main Methods:
- Male Swiss Webster mice were fed a diet containing 2.5% griseofulvin (GF).
- Light and electron microscopy were used to examine liver tissues serially.
- Histopathological changes, including Mallory body formation, were analyzed.
Main Results:
- GF induced progressive hepatic alterations, including hepatomegaly, necrosis, mitosis, Kupffer cell activation, bile duct proliferation, and fibrosis.
- Protoporphyrin crystals and hepatocellular hyalin, resembling Mallory bodies (MB), were observed.
- Ultrastructural analysis revealed distinct MB types and associated cellular changes, suggesting a common pathway for liver injury.
Conclusions:
- Griseofulvin (GF) is a potent hepatotoxin in mice, inducing a spectrum of liver damage.
- The formation of hepatocellular Mallory bodies (MB) in GF-fed mice mirrors that seen in human alcoholic liver disease.
- These findings suggest a conserved cellular response pathway to diverse hepatotoxic insults.
