THE EFFECT OF MEXIDOL ON GLUTATHIONE SYSTEM IN RAT BRAIN UNDER MODELING OF PARKINSON’S DESEASE
I.M. Mankovska, O.O. Gonchar, L.V. Bratus
O.O. Bogomolets Institute of Physioligy National Academy of
Sciences of Ukraine, Kyiv, Ukraine
We studied the effects of mexidol (3-oxy-6-methyl-2-ethylpiridine succinate) on the antioxidant glutathione system in
rat brain mitochondria in experimental Parkinson’s disease
induced by rotenone administration. Wistar rats were divided
into the following groups of 6 in each: I - intact rats (control);
II - rotenone (3 mg/kg per day) was injected subcutaneously
for 2 weeks; III - after rotenone intoxication, mexidol (50
mg/kg per day) was injected intraperitoneally for 2 weeks. In
the suspension of brain mitochondria, the activity of NADH
dehydrogenase (complex I of the mitochondrial respiratory
chain), content of the active products of 2-thiobarbituric acid
(TBA-AP), the reduced (GSH) and oxidized (GSSG) glutathione amounts, the activity of glutathione-dependent enzymes:
glutathione peroxidase (GP) and glutathione reductase (GR) as
well as NADH+-isocitrate-dehydrogenase activity (NADPH+-
ICDH) were measured. The activity and protein expression
of MnSOD and GP in rat brain mitochondria were estimated.
Treatment of rats with mexidol led to a weakening of oxidative processes in brain mitochondria in comparison with rats
exposed to rotenone intoxication. It was shown that intraperitoneal injections of mexidol led to a decrease in the TBA-AP and
in the GSSG content and to an increase in GSH/GSSG ratio in comparison with rotenone intoxication. It was also registered
an increase in the activity of NADH-dehydrogenase. Such
changes indicated a weakening of the mitochondrial oxidative
processes intensity. Treatment of rats with mexidol promoted
an increase in GSH content, GR and NADPH+-ICDH activities
in brain mitochondria in comparison with rotenone administration. Treatment with mexidol resulted to an increased activity
and protein expression of GP and MnSOD. We conclude that
mexidol reduced the rotenone-induced damage of rat brain
mitochondria increasing the action of glutathione-dependent
and NADPH+-generating enzymes.
mexidol; rotenone; brain; mitochondria; oxidative processes; glutathione antioxidant system.
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