Specific features of sacricin action on the disturbances in phospholipid metabolism during seizures

Abstract

1 is a brain disease characterized by strong hyperactivity of neuronal populations. The goal of our research was to study different aspects of lipid metabolism in different phases of convulsive body response, namely, before and after a sacricin injection. Sacricin, a derivative of polycyclic carboxylic acid, possesses rather large anticonvulsant effect. The phospholipid (PL) extraction was performed with the use of Folch method [1], using Karagezyan’s modification [2]. PLs were fractionated by one-dimensional ascending chromatography in a thin layer of silica gel (Merk, Germany) using the solvent system chloroform : methanol : ammonia (65 : 35 : 5). Convulsive activity is characterized by disturbances of membrane-bound enzyme functional activity, a decrease in the number of receptors, increase in “flip-flop” transfers of phospholipids, and probable hydrolysis of phosphatidylinositols, which are involved in nerve impulse transfer and affect transport of PLs and diglyceride, which are secondary messengers [3, 4] responsible for maintenance of the functional activity of a cell. Taking into consideration the role of lipids in the structure‐functional organization of biological membranes [5, 6], we studied PL‐PL conversions in the brain cortex and cerebellum of rats during pentylenetetrazol seizures in the presence and absence of sacricin. Based on the presented results, we assumed the following: the convulsions enhanced the activity of phospholipase A 2 , which catalyzes reactions of PL deacyla1 Corresponding author; address: Hasratyan St. 7, Yerevan 0014, Armenia; e-mail: art79@rambler.ru tion and the formation of nonesterified fatty acids, which are substrates for the formation of a large quantity of lipid peroxides. We observed qualitative and quantitative shifts in the PL-PL ratio. Especially strong shifts were observed in the contents of phosphatidylcholines, phosphatidylserines, and mainly in lysophosphatidylcholines, which are the products of lysis of phosphatidylcholines. Injection of sacrisin strongly normalized PL metabolism and lipid peroxidation. The molecular mechanisms of the normalizing effect of this drug are associated with systems that regulate the reactions of PL‐PL interactions and peroxidation of lipids.