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[Comparative hepatic toxicity of perhexiline maleate and griseofulvin in mice]
Abstract:
Hepatic toxicity was observed in mice which had received Griseofulvin or Perhexilin Maleate over a period of several months. Treatment of griseofulvin alone gave rise to hepatitis with the presence of Mallory bodies (MB) whereas the same length of treatment with Perhexilin Maleate was associated with steatonecrosis with an absence of MB. When treatment was followed by a one month rest period hepatic lesions disappeared with no trace of sequelae. Cross-treatment studies showed that one week of Perhexiline Maleate was sufficient to induce MB in mice pretreated with Griseofulvin. Similarly, Griseofulvin administered to mice pretreated with Perhexilin Maleate gave rise to MB formation after one week as opposed to the usual two months incubation time (DENK et al.). The histological nature and mode of formation of these MB was identical to that encountered in acute alcoholic hepatitis. On addition, combined drug therapy employing Perhexilin Maleate suggests a particular hepatic toxicity in man in cases where the liver has become predisposed due to other therapeutic.
Insights
Griseofulvin and Perhexiline Maleate cause liver damage in mice, forming Mallory bodies (MB) or steatonecrosis. Reversible lesions indicate potential drug interactions and predisposed liver toxicity.
Area of Science:
- Hepatology
- Toxicology
- Drug-induced liver injury
Background:
- Griseofulvin and Perhexiline Maleate are known to cause hepatic toxicity.
- Mallory bodies (MB) are characteristic histological findings in certain liver conditions.
Purpose of the Study:
- To investigate the hepatic toxicity of Griseofulvin and Perhexiline Maleate in mice.
- To characterize the histological changes and the formation of Mallory bodies induced by these drugs.
- To explore the effects of combined drug therapy and rest periods on liver lesions.
Main Methods:
- Mice were treated with Griseofulvin or Perhexiline Maleate for several months.
- Histological examination was performed to identify liver damage and Mallory bodies.
- Cross-treatment studies and rest periods were incorporated to assess drug interactions and reversibility.
Main Results:
- Griseofulvin induced hepatitis with Mallory bodies; Perhexiline Maleate caused steatonecrosis without MB.
- Liver lesions resolved after a one-month rest period.
- Pretreatment with one drug significantly shortened the incubation time for Mallory body formation by the other drug.
Conclusions:
- Both Griseofulvin and Perhexiline Maleate induce distinct forms of hepatic toxicity in mice.
- Mallory body formation induced by these drugs resembles that seen in alcoholic hepatitis.
- Combined therapy may potentiate liver toxicity, especially in predisposed individuals.