Usnic acid reactive metabolites formation in human, rat, and mice microsomes. Implication for hepatotoxicity. (October 2018)

• Record Type: Journal Article
• Authors: Piska, Kamil; Galanty, Agnieszka; Koczurkiewicz, Paulina; Żmudzki, Paweł; Potaczek, Joanna; Podolak, Irma; Pękala, Elżbieta
• Is Part Of: Food and chemical toxicology. Volume 120(2018)
• Page Start: 112
• Page End: 118
• Publication Date: 2018-10
• Subjects: Usnic acid -- Liver failure -- Reactive metabolites -- Drug toxicity -- Hepatotoxicity; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.07.005
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Usnic acid is a lichen compound which is extensively studied due to its cytotoxic, antiproliferative, antimicrobial, antiviral, antiprotozoal, and anti-inflammatory activities. Despite a broad spectrum of biological properties, usnic acid is a hepatotoxic agent, thus its potential use as a drug is limited. Certain hepatotoxic drugs may act by generating reactive metabolites that damage the liver. The aim of the study was to predict the biotransformation of usnic acid enantiomers to reactive products using a trapping assay with glutathione in human, rat, and mice liver microsomes. Our results indicate that each enantiomer forms two reactive metabolites; in turn, these metabolites form adducts with glutathione, which may partially explain the toxicity of usnic acid. In silico analysis indicated structural alerts for the generation of reactive metabolites in usnic acid formula. This study proposes a novel mode of the hepatic toxicity of usnic acid enantiomers; it also provides some useful suggestions for designing safer usnic acid derivatives. Highlights: Biotransformation of usnic acid leads to the formation of its reactive metabolites, detectable by trapping assay. There are differences between usnic acid enantiomers and between microsomal models in the formation of its reactive products. Reactive metabolites formation may partially explain usnic acid hepatotoxicity.