Korean J Physiol Pharmacol.  1998 Aug;2(4):427-433.

Cytoprotective effects of dihydrolipoic acid and lipoic acid on the oxidative stress in cultured rat cortical neurons

• Kim WK

Abstract

In brain hypoxic-ischemia, an excess release of glutamate and a marked production of reactive oxygen species (ROS) occur in neuronal and non-neuronal cells. The present study investigated the effect of the biological antioxidants dihydrolipoic acid (DHLA) and lipoic acid (LA) on N-methyl-D-aspartate (NMDA)and ROS-induced neurotoxicity in cultured rat cortical neurons. DHLA enhanced NMDA-evoked rises in intracellular calcium concentration ((Ca2+)i). In contrast, LA did not alter the NMDA-evoked calcium responses but decreased after a brief treatment of dithiothreitol (DTT), which possesses a strong reducing potential. Despite the modulation of NMDA receptor-mediated rises in (Ca2+)i, neither DHLA nor LA altered the NMDA receptor-mediated neurotoxicity, as assessed by measuring the amount of lactate dehydrogenase released from dead or injured cells. DHLA, but not LA, prevented the neurotoxicity induced by xanthine/xanthine oxidase-generated superoxide radicals. Both DHLA and LA decreased the glutathione depletion-induced neurotoxicity. The present data may indicate that biological antioxidants DHLA and LA protect neurons from ischemic injuries via scavenging oxygen free radicals rather than modulating the redox modulatory site(s) of NMDA receptor.

Keyword

[Ca2+]i; Neurotoxicity, Dihydrolipoic acid (DHLA); Lipoic acid (LA); NMDA receptor; Glutathione; Reactive oxygen species (ROS)

MeSH Terms

8,11,14-Eicosatrienoic Acid
Animals
Antioxidants
Brain
Calcium
Dithiothreitol
Free Radicals
Glutamic Acid
Glutathione
L-Lactate Dehydrogenase
N-Methylaspartate
Neurons*
Oxidation-Reduction
Oxidative Stress*
Oxygen
Rats*
Reactive Oxygen Species
Superoxides
Thioctic Acid*
8,11,14-Eicosatrienoic Acid
Antioxidants
Calcium
Dithiothreitol
Free Radicals
Glutamic Acid
Glutathione
L-Lactate Dehydrogenase
N-Methylaspartate
Oxygen
Reactive Oxygen Species
Superoxides
Thioctic Acid