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Experimental induction of hepatocellular hyalin (Mallory bodies) in mice by griseofulvin treatment. 1. Light
Abstract:
Griseofulvin (GF) feeding of mice resulted in protoporphyria, liver cell damage, bile duct alterations, and finally hepatoma formation. In addition, hepatocellular hyalin developed, resembling in its morphology classic Mallory bodies (MB) as seen in alcoholic and nonalcoholic liver disorders in man. Liver cells containing MB often displayed features of severe cell damage and MB were finally released into the sinusoids and degraded by macrophages. The rapid disappearance of MB following GF discontinuation and the reappearance after resumption of GF feeding suggest an intimate relationship between metabolic alterations in the hepatocytes exerted by the drug and MB formation. This assumption is further supported by the fact that MB change their tinctoreal properties in chromotrope aniline blue-stained sections after GF discontinuation, possibly relfecting degeneration. Long term GF treatment apparently primed the liver for MB formation since the cells were able to respond almost instantly with MB to a GF challenge after a 1-month GF-free period.
Insights
Griseofulvin (GF) causes liver damage and hepatoma in mice, forming Mallory bodies (MB) in liver cells. MB formation is reversible upon drug withdrawal, indicating a direct link to GF-induced metabolic changes.
Area of Science:
- Hepatology
- Toxicology
- Experimental Pathology
Background:
- Griseofulvin (GF) is an antifungal medication.
- Hepatocellular hyalin, resembling Mallory bodies (MB), is observed in various human liver diseases.
Purpose of the Study:
- To investigate the effects of Griseofulvin (GF) on liver pathology in mice.
- To characterize the formation and resolution of hepatocellular hyalin (Mallory bodies) induced by GF.
Main Methods:
- Mice were fed Griseofulvin (GF) to induce liver damage and hepatoma.
- Histopathological examination of liver tissues was performed.
- Morphological and tinctorial properties of Mallory bodies (MB) were analyzed.
Main Results:
- GF feeding led to protoporphyria, liver cell damage, bile duct alterations, and hepatoma formation.
- Hepatocellular hyalin, morphologically similar to Mallory bodies (MB), developed in hepatocytes.
- MB formation was reversible upon GF discontinuation and reappeared upon resumption, suggesting a direct drug-induced metabolic link.
Conclusions:
- Griseofulvin (GF) induces liver injury and hepatoma formation in mice.
- The formation of hepatocellular hyalin (Mallory bodies) is a reversible consequence of GF-induced metabolic alterations.
- GF-treated livers are primed for rapid MB formation upon re-exposure to the drug.