4.4 Review

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

Journal

DRUG METABOLISM AND DISPOSITION
Volume 50, Issue 5, Pages 655-670

Publisher

AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.121.000458

Keywords

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Funding

  1. National Natural Science Foundation of China [81773813, U1812403, 81830104]

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This review explores the relationship between metabolic activation and hepatotoxicity of furan-containing compounds, focusing on several typical alkylated furans, synthetic pharmaceuticals, and components extracted from herbal medicines. The pharmacological activities and evidence of liver injuries caused by these compounds are described, and potential toxic mechanisms are discussed based on previous research. The article provides insights for seeking solutions and preventing toxic effects in clinical practice.
Furan-containing compounds are abundant in nature, and many, but not all, have been found to be hepatotoxic and carcinogenic. The furan ring present in the chemical structures may be one of the domineering factors to bring about the toxic response resulting from the generation of reactive epoxide or cis-enedial intermediates, which have the potential to react with biomacromolecules. This review sets out to explore the relationship between the metabolic activation and hepatotoxicity of furan-containing compounds on the strength of scientific reports on several typical alkylated furans, synthetic pharmaceuticals, and components extracted from herbal medicines. The pharmacological activities as well as concrete evidence of their liver injuries are described, and the potential toxic mechanisms were discussed partly based on our previous work. Efforts were made to understand the development of liver injury and seek solutions to prevent adverse effects. SIGNIFICANCE STATEMENT This review mainly elucidates the vital role of metabolic activation in the hepatotoxicity of furan-containing compounds through several typical chemicals studied. The possible mechanisms involved in the toxicities are discussed based on collective literatures as well as our work. Additionally, the structural features responsible for toxicities are elaborated to predict toxicity potentials of furan-containing compounds. This article may assist to seek solutions for the occurring problems and prevent the toxic effects of compounds with furan(s) in clinical practice.

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