EFFECT OF LIPOIC ACID ON REDOX STATE OF COENZYME-Q IN MICE TREATED WITH 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND DIETHYLDITHIOCARBAMATE

We investigated the effects of a combined treatment of male C57Bl/6 mi ce with diethyldithiocarbamate and 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP) in the absence or presence of different forms of lipo ic acid (Thioctacid T(R). commonly used for treatment of diabetic poly neuropathies) on levels and redox states of alpha-tocopherol and coenz yme Q in vivo and on activities of various enzymes of energy metabolis m ex vivo. Treatment of mice with diethyldithiocarbamate plus MPTP res ulted in a decrease in dopamine (67%) and its major metabolites dihydr oxyphenylacetic acid (38%) and homovanillic acid (37%) in striatum. al pha-Tocopherol levels were unaltered in striatum; however, the reduced forms of coenzyme Q were decreased in frontal cortex and hippocampus following diethyldithiocarbamate plus MPTP. In frontal cortex activity of NADH dehydrogenase was significantly inhibited by diethyldithiocar bamate plus MPTP ex vivo, suggesting that the neurotoxic metabolite of MPTP, 1-methyl-4-phenylpyridinium ion, is acting in brain regions oth er than striatum as well. Lipoic acid, administered 6 times, each at 9 0 min prior to MPTP, could not restore dopamine in striatum but in con trast maintained a normal ratio of the reduced form to the oxidized fo rm of coenzyme Q, suggesting an interaction of lipoic acid with energy metabolism which seems, however, not only to be due to an activation of pyruvate dehydrogenase.