E.V. Belova - Ph.D. (Biol), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com N.N. Klyueva - Ph.D. (Biol), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com A.G. Vinogradov - Ph.D. (Biol), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com N.M. Kalachnikova - Junior Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com E.V. Ageeva - Ph.D. (Med), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail:elena_ag@inbox.ru I.V. Okunevich - Ph.D. (Biol), Senior Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: irina_okunevich@mail.ru N.S. Parfenova - Ph.D. (Med), Senior Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nina.parf@mail.ru T.V. Vinogradova - Ph.D. (Biol), Senior Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com

A novel derivate of trapedil (rokornal) is widely used as a dilator of coronary arteries and as a lipid-lowering agent, it is non-toxic, effective as lipid-lowering agent, normalizes lipid and lipoprotein metabolism. The purpose of the work is to study the effect of trapedil derivate on lipoprotein and lipid metabolism in different dislipoproteidemias models. Studies were carried out on male rats and guinea pigs. Hyperlipidemia was induced in rats in two ways: using a diet enriched in cholesterol (CH) with addition of 6-methylthiouracil and without it. In guinea pigs the cholesterol diet was used with fats. Trapedil (TL) and clofibrate were used as reference drugs to a trapedil derivate (DTL). Previously the acute toxicity was studied in mice. DTL was 10 times less toxic. LD-50 TL was 0.6 g/kg body weight, for DTL  6.0 g/kg. The animals received TL and DTL with diet. TL was used at a dose of 30 mg/kg, DTL  150 and 300 mg/kg. Duration was 20 days. Lipid parameters in blood serum sampling and in liver were determined. CH, triglycerides (TG) and HDL-CH were determined in blood serum. CH and TG levels in samples of liver were determined, after preliminary extraction of lipids. LDL-CH and atherogenic index were calculated by the known formulas. Lipid content was determined by enzymatic method using Randox kits (England). Separation lipoprotein (LP) serum was carried using density gradient ultracentrifugation. First of all, I would like to note that in all the experiments with introduction of the TL drug pathological aggression of animals was observed, and it increased with increasing dose. A similar phenomenon was not observed when using DTL. The content of cholesterol in the blood and in the liver decreased in animals exposed to human trafficking and DTL. Both drugs normalized abnormal hyperlipidemia serum lipoprotein spectrum. However, the effect of DTL was significantly greater for restoration of high-density lipoprotein, decreased in the dyslipoproteindemiia. The trapedil derivate was less active in reduction of the simulated dislipoproteindemias than trapedil. However, DTL has no negative effects on animals, in contrast to the reference drug and has a much lower toxicity and thus can be recommended as lipid-lowering agents.

 

1. Ryzhenkov V.E., Okunevich I.V., Kljueva N.N., Soloveva M.A., Trjufanov V.F. Gipolipidemicheskaja aktivnost veshhestv prirodnogo proiskhozhdenija // EHksperimentalnaja i klinicheskaja farmakologija. 1992. №5. S. 60-63.
2. Kljueva N.N., Vinogradova T.V., Kalashnikova N.M., SHatilina L.V., Okunevich I.V., Belova E.V. Gipolipidemicheskoe dejjstvie razlichnykh flavonoidov v uslovijakh ehksperimentalnykh narushenijj lipidnogo obmena // Tezisy dokladov konferencii, posvjashhennojj 100-letiju S.V. Anichkova. SPb. Sentjabr 2013.
3. Ryushenkov V.E., Okunevich I.V., Klyueva N.N., Solovjva M.A., Trufanov V.F. Search and study new hypolipidemic drugs // In Abstract of Intern. Conference. 1992. 6-8 oct. P. 190.