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Related Experiment Video

Updated: Jun 17, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Troglitazone.

Tsuyoshi Yokoi¹

¹Drug Metabolism and Toxicology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. tyokoi@kenroku.kanazawa-u.ac.jp

Handbook of Experimental Pharmacology

|December 19, 2009

Summary

Troglitazone, an early antidiabetic drug, was withdrawn due to liver damage. Its unique structure may form toxic metabolites, but the exact mechanism of its idiosyncratic hepatotoxicity remains unclear.

Area of Science:

Pharmacology
Toxicology
Biochemistry

Background:

Troglitazone was the first thiazolidinedione approved for diabetes treatment in 1997.
It was withdrawn in 2000 due to severe idiosyncratic hepatotoxicity.
The drug's chroman ring, similar to vitamin E, can be metabolized into reactive species.

Purpose of the Study:

To summarize proposed mechanisms of troglitazone-induced hepatotoxicity.
To review in vivo and in vitro studies investigating troglitazone's toxicity.
To discuss the controversial role of reactive metabolites in troglitazone cytotoxicity.

Main Methods:

Review of in vivo and in vitro toxicological studies.
Analysis of proposed metabolic pathways of troglitazone.

Related Experiment Videos

Last Updated: Jun 17, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Examination of studies on troglitazone-induced apoptosis.

Main Results:

Troglitazone's chroman structure can generate reactive metabolites (quinones, radicals, epoxides).
Troglitazone induces apoptosis in various cell types, but metabolite involvement is debated.
Despite extensive testing, a definitive mechanism for its idiosyncratic hepatotoxicity is not established.

Conclusions:

The exact mechanism of troglitazone's idiosyncratic hepatotoxicity is complex and not fully elucidated.
Multiple factors likely contribute to the liver injury observed in some individuals.
Further research is needed to fully understand the drug's toxicological profile.