The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells

Jacoba Flier, Freek L Van Muiswinkel, Cornelis A M Jongenelen, Benjamin Drukarch

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56 Citations (Scopus)


alpha-Lipoic acid (LA), an antioxidant with broad neuroprotective capacity, is thought to act by scavenging reactive oxygen species and stimulation of glutathione synthesis. LA shows structural resemblance to dithiolethiones, like anethole dithiolethione (ADT). ADT protects against oxidative damage, primarily by induction of phase II detoxication enzymes, in particular NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase (GST). Therefore, we investigated whether LA, like ADT, is capable also of inducing these protective enzymes. Our data show that LA, like ADT, induces a highly significant, time- and concentration dependent, increase in the activity of NQO1 and GST in C6 astroglial cells. The LA or ADT mediated induction of NQO1 was further confirmed by quantitative PCR and western blot analysis. This work for the first time unequivocally demonstrates LA mediated upregulation of phase II detoxication enzymes, which may highly contribute to the compounds' neuroprotective potential. Moreover, the data support the notion of a common mechanism of action of LA and ADT.

Original languageEnglish
Pages (from-to)695-9
Number of pages5
JournalFree radical research
Issue number6
Publication statusPublished - Jun 2002


  • Anethole Trithione
  • Animals
  • Antioxidants
  • Astrocytes
  • Astrocytoma
  • Central Nervous System Neoplasms
  • Glutathione Transferase
  • Inactivation, Metabolic
  • Journal Article
  • NAD(P)H Dehydrogenase (Quinone)
  • Neuroprotective Agents
  • Oxidoreductases
  • Rats
  • Thioctic Acid
  • Transferases
  • Tumor Cells, Cultured

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