Related Experiment Video
Updated: Jan 9, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Metabolic activation, hepatic protein covalent binding, and cytotoxicity of arctigenin
Yuqin Chen1, Zixia Hu1, Guode Zhao1
1Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
Abstract:
Arctigenin (ATG) is an important component isolated from the fruit of the medicinal plant Arctium lappa L., with anti-inflammatory, antiviral and anti-tumor properties. Although ATG has been reported to induce hepatotoxicity in beagle dogs and SD rats, and the underlying mechanisms remained unclear. The aim of this study was to investigate the metabolic activation of ATG and to define the potential correlation between the metabolic activation of ATG and its hepatotoxicity. A quinone methide intermediate was identified in vitro and in vivo, and CYP3A dominated the metabolic activation. ATG was found to show significant cytotoxicity at 50 μM in cultured mouse primary hepatocytes. The ATG-derived quinone methide metabolite assaulted cysteine residue of hepatic protein to form protein covalent binding. The observed protein modification was most likely associated with the cytotoxicity of ATG observed.
Related Concept Videos
Drug Metabolism: Phase II Reactions
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Mutagenicity and Carcinogenicity
Hepatic Drug Clearance: Effect of Protein Binding
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
GPCRs Regulate Adenylyl Cylase Activity

