Me. Gotz et al., 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, European journal of pharmacology. Molecular pharmacology section, 266(3), 1994, pp. 291-300
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.