The influence of salt regimes of the diet on the course of the convulsive syndrome and their modulation of the effect of sodium valproate
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Keywords

high-sodium diet, table salt substitute, pentylenetetrazole, seizure syndrome, sodium valproate

Abstract

The prevalence of epilepsy, the difficulty of controlling seizures in every third patient, and the high percentage of side effects of antiepileptic drugs determine the expediency of finding new approaches to

improving the treatment of the disease. A promising way is to correct the mineral composition of the diet, in particular, with the help of a low-sodium table salt substitute.

The aim of the study is to compare the effect of a high-sodium diet and a table salt substitute “Nedosol” on the anticonvulsant effect of the classic antiepileptic drug – sodium valproate.

The work was performed at the Educational and Scientific Institute of Applied Pharmacy of the National University of Pharmacy (Kharkiv) using white non-linear male mice. For one month, part of the animals were given exclusively 1% solution of table salt as a drink, the other part, instead of water, consumed 1% solution of table salt substitute “Nedosol” (LEDA LLC, Kharkiv), 100.0 g of which contains: sodium chloride – 35.0 g, potassium chloride – 25.0 g, potassium citrate – 5.0 g, potassium bromide – 0.5 g, magnesium asparaginate – 15.0 g, magnesium citrate – 4.5 g, calcium gluconate – 10.0 g, glutamic acid – 5.0 g. Mice of the control group were on a regular water regime with unlimited access to settled tap water. After 1 month, pentylenetetrazole-induced seizures were reproduced in mice (pentylenetetrazole at a dose of 90 mg/kg subcutaneously); in this case, part of the animals of each group (control) was pre-administered intragastric water, the other part – sodium valproate (Depakin, Sanofi-Aventis, France, syrup for oral use) at a dose of 150 mg/kg; and standard indicators of the course of the convulsive syndrome were recorded.

It has been established that a high-sodium diet aggravates the course of pentylenetetrazole-induced seizures, while the table salt substitute “Nedosol” helps to reduce the severity of model pentylenetetrazole- induced paroxysms by suppressing tonic extension. Moreover, it was investigated that against the background of a high-sodium diet, the protective effect of sodium valproate in 1⁄2 ED50 is less pronounced than under the conditions of a normal mineral composition of the diet and is manifested only as a tendency. The effectiveness of sodium valproate against the background of the table salt substitute “Nedosol”, on the contrary, is significantly enhanced, which is determined by a statistically significant extension of the latency period of attacks, a decrease in the number of seizures by 1 mouse (primarily due to the reduction of more severe tonic convulsions), as well as by the main integral indicator of efficiency – by reliable decrease in animal mortality relative to standard and high-sodium rations.

Thus, the low-sodium table salt substitute “Nedosol” significantly enhances the anticonvulsant effect of sodium valproate in a subeffective dose. The results obtained indicate the expediency of regulating the mineral composition of the food diet as a promising direction for improving the pharmacotherapy of epilepsy.

https://doi.org/10.33250/18.02.098
pdf (Українська)