Comparison of influence of lamotrigine and other anticonvulsants on nitric oxide and thiol-disulfide systems in conditions ofmetrazole kindling

Abstract

Natalia P. Shastun, Valentina I. Opryshko, Nina V. Buchtiarova,Sergii V. Levich

Objective: Epilepsy and seizure disorders are of the most widespread and serious diseases of the central nervous system (CNS), leading to disability of the patient and to reducing life quality. Seizure disorders are associated with increasing of electrical activity of neurons of the CNS. Heightened electrogenesis of neurons are accompanied with activation of the nitric oxide (NO) system that, by generating of oxidizing agents, leads to damage of the cells and the formation of ‘structural footprint’ of seizures. This study is focused on the effects of anticonvulsants on the level of NO concentration, NO-synthase (NOS) activity and parameters of the thiol-disulfide system in conditions of equivalents of epilepsy. Methods: Research has been carried out on sufficient number of experimental animals. For biochemical and histo-immunochemical study brain tissue of experimental animals was used. We studied: density of inducible (i) and neuronal (n)NOS positive neurons in the sensorimotor cortex layers; content of nitrotyrosine, thiol groups, recovered and oxidized glutathione and activity of glutathione reductase in the brain homogenate. Results: The simulation of seizures by metrazole led to increase in the expression of iNOS and nNOS with the background of deficiency thiol recovery. Preventative administration of lamotrigine, carbamazepine, topiramate, sodium valproate or gabapentin normalized the shifts in the NO and thiol systems, but varied from each other. Conclusions: Obtained results allowed to suggest that the functional and biochemical system of NO is one of the links of anticonvulsants action. The most pronounced effect that led to decrease in the expression of the two isoforms of NOS was observed with administration of lamotrigine.