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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
Volume36
Issue number6
Publication statusPublished - Jun 2002

Cite this

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title = "The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells",
abstract = "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.",
keywords = "Anethole Trithione, Animals, Antioxidants, Astrocytes, Astrocytoma, Central Nervous System Neoplasms, Glutathione Transferase, Inactivation, Metabolic, NAD(P)H Dehydrogenase (Quinone), Neuroprotective Agents, Oxidoreductases, Rats, Thioctic Acid, Transferases, Tumor Cells, Cultured, Journal Article",
author = "Jacoba Flier and {Van Muiswinkel}, {Freek L} and Jongenelen, {Cornelis A M} and Benjamin Drukarch",
year = "2002",
month = "6",
language = "English",
volume = "36",
pages = "695--9",
journal = "Free radical research",
issn = "1029-2470",
publisher = "Informa Healthcare",
number = "6",

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The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. / Flier, Jacoba; Van Muiswinkel, Freek L; Jongenelen, Cornelis A M; Drukarch, Benjamin.

In: Free radical research, Vol. 36, No. 6, 06.2002, p. 695-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells

AU - Flier, Jacoba

AU - Van Muiswinkel, Freek L

AU - Jongenelen, Cornelis A M

AU - Drukarch, Benjamin

PY - 2002/6

Y1 - 2002/6

N2 - 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.

AB - 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.

KW - Anethole Trithione

KW - Animals

KW - Antioxidants

KW - Astrocytes

KW - Astrocytoma

KW - Central Nervous System Neoplasms

KW - Glutathione Transferase

KW - Inactivation, Metabolic

KW - NAD(P)H Dehydrogenase (Quinone)

KW - Neuroprotective Agents

KW - Oxidoreductases

KW - Rats

KW - Thioctic Acid

KW - Transferases

KW - Tumor Cells, Cultured

KW - Journal Article

M3 - Article

VL - 36

SP - 695

EP - 699

JO - Free radical research

JF - Free radical research

SN - 1029-2470

IS - 6

ER -