Thiophene is toxic to cerebellar granule cells in culture after bioactivation by rat liver enzymes

  • Dreiem A
  • Fonnum F
  • 10


    Mendeley users who have this article in their library.
  • 13


    Citations of this article.


Several compounds that are not neurotoxic by themselves can cause toxic effects in vivo after enzymatic bioactivation. Thiophene is an industrial solvent known to produce degeneration primarily of the granule cells in the cerebellum when administered to animals in vivo. The mechanism for thiophene toxicity is not known, although it has been suggested that thiophene metabolism may lead to formation of oxidative intermediates that could function as the ultimate toxicants. In the present work we have used rat cerebellar granule cells (CGCs) in culture combined with rat liver postmitochondrial (S9) fraction as a source of biotransformation enzymes to test the toxicity of thiophene in vitro. The results demonstrate that thiophene is toxic to rat cerebellar granule cells in culture only after biotransformation. Furthermore, the toxic effects were reduced by cytochrome P450 (CYP) inhibitors and by scavengers of reactive molecules (α-tocopherol, reduced glutathione, and phenyl-N-tert- butylnitrone). These findings support the hypothesis that thiophene requires metabolism to produce the ultimate toxicant, and that the cytochrome P450 enzyme system is involved in the metabolism. © 2004 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Biotransformation
  • Cerebellar granule cells
  • Cytochrome P450
  • Neuronal degeneration
  • Thiophene

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Anne Dreiem

  • Frode Fonnum

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free