The endogenous cofactors, thioctic acid and dihydrolipoic acid, are neuroprotective against NMDA and malonic acid lesions of striatum.
Thioctic acid (alpha-lipoic acid) and dihydrolipoic acid are endogenous, interconvertible cofactors of the mitochondrial pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. These compounds help to maintain glutathione and alpha-tocopherol in their reduced states, and they possess intrinsic free radical scavenging properties. We examined whether systemic treatment with thioctic acid or dihydrolipoic acid is protective against direct- and indirect-acting excitotoxins. Adult rats were treated for 10 days with intraperitoneal injections of vehicle, thioctic acid or dihydrolipoic acid, and on day 7 of treatment animals received unilateral stereotaxic injections of NMDA or malonic acid into the striatum. Histological assessment 3 days after the stereotaxic injections revealed a marked reduction in lesion volume in animals treated with thioctic acid or dihydrolipoic acid. We conclude that thioctic acid and dihydrolipoic acid are neuroprotective against direct and indirect excitotoxic insults.
Greenamyre
J T
JT
Department of Neurology, University of Rochester Medical Center, NY 14642.
Garcia-Osuna
M
M
Greene
J G
JG
D000818:Animals; D007274:Injections, Intraperitoneal; D008297:Male; D008314:Malonates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017072:Neostriatum / Q000166:cytology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D008314:Malonates; D016202:N-Methylaspartate; D008063:Thioctic Acid; C015144:dihydrolipoic acid