It was established that ischemic neurodistraction is accompanied by all NO-synthases isoforms expression disturbance, NO hyperproduction, and its toxic effect [1].
The aim of the study — to investigate the NO system condition and NO-associated chains of the cerebral ischemia on the ground of the correction with antioxidant medications (Tiotriasoline, Mexidol).
Methods and materials. Disturbance of the cerebral blood circulation was made by doubleside ligation of the Carotid arteries on the 1st and 4th day in laboratory rats with weight 200–250 g. General NO-synthase (NOS) activity was determined by fluorometric method. Nitrotyrosine (NTS) was detected in the cerebral homogenate by hardface immunosorbent method. Mitochondrial pore (MP) opening was detected after initiation with Cyclosporine-A, membrane potential of the mitochondrial charge (MPMC) — with Saphronine-O [6]. Carbohydrate-energetic metabolism processes were assessed by chromatographic detection of the adenine nucleotides in the brain homogenate. Inducible NOS (iNOS), endothelial NOS (eNOS), neuronal NOS (nNOS) expression intensity was studied by histochemical method.
Results and discussion. Experiment’s results showed that doubleside occlusion of the Carotid arteries during 1st day leaded to the global changes in the NO system, general NOS activity and expression of the neuronal (by 55%) and inducible (by 59%) isoforms. NOS activity increase leaded to the nitrosyl stress. Excess of the NO and its toxic derivates suppresses proteins from the mitochondrial breath-chain, injury of the internal mitochondrial membrane and opening of the MP and occurrence of the mitochondrial dysfunction (MD). Tiotriasoline (50 mg/kg) and Mexidol (50 mg/kg) injection have positive effect on the NOS activity and expression of its isoforms.
Positive influence of the antioxidants explains its stabilizing action on the functional mitochondrial activity. Tiotriasolin and Mexidol administration normalized carbohydrate-energetic metabolism that was confirmed by ATF level and mitochondrial charge increase. Tiotriasolin exceeded Mexidol activity.