Reactive metabolites in the biotransformation of molecules containing a furan ring

Chem Res Toxicol. 2013 Jan 18;26(1):6-25. doi: 10.1021/tx3003824. Epub 2012 Oct 24.

Abstract

Many xenobiotics containing a furan ring are toxic and/or carcinogenic. The harmful effects of these compounds require furan ring oxidation. This reaction generates an electrophilic intermediate. Depending on the furan ring substituents, the intermediate is either an epoxide or a cis-enedione with more ring substitution favoring epoxide formation. Either intermediate reacts with cellular nucleophiles such as protein or DNA to trigger toxicities. The reactivity of the metabolite determines which cellular nucleophiles are targeted. The toxicity of a particular furan is also influenced by the presence of competing metabolic pathways or efficient detoxification routes. GSH plays an important role in modulating the harmful effects of this class of compound by reacting with the reactive metabolite. However, this may not represent a detoxification step in all cases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism
  • Furans / chemistry
  • Furans / metabolism*
  • Furans / toxicity
  • Glutathione / metabolism
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction

Substances

  • Furans
  • Cytochrome P-450 Enzyme System
  • Glutathione