N.S. Parfenova - Ph.D. (Med), Senior Research Scintist, Institute of Experimental Medicine, Saint-Petersburg, Russia. Е-mail: nina.parf@mail.ru N.N. Klyueva - Ph.D. (Biol.), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com N. Nikulcheva - Dr.Sc. (Med.), Leading Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com E.V. Belova - Ph.D. (Biol.), Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: nnklyueva@gmail.com T.V. Vinogradova - Ph.D. (Biol.), Senior 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 I.V. Okunevich - Ph.D. (Biol.), Senior Research Scientist, Institute of Experimental Medicine, Saint-Petersburg, Russia. E-mail: irina_okunevich@mail.ru

The purpose of the study was to investigate the experimental lipid-lowering activity of the enzyme cholesterol oxidaze of microbial origin. The paper presents the data in the three kinds of experimental animals with dyslipidemia (DLP), where lipid-lowering activity of the enzyme of microbial origin cholesterol oxidaze (CH-ox) capable of oxidizing cholesterol (CH) is found. Under the action of CH-ox, serum lipid profile improved significantly, irregularities in the DLP: reduced cholesterol (LDL) of atherogenic lipoproteins (LP) of low and intermediate density and the concentration of HDL antiatheroge high-density increases. For the experiments male mongrel adult animals: rats, guinea pigs and rabbits were used. The experimental DLP was induced in different ways, using diets enriched with cholesterol. In experiments highly purified CH-ox (obtained by microbial synthesis followed by chemical treatment in the St. Petersburg Institute of Antibiotics) was used. The drug CH-ox had a very low toxicity, was investigated at various doses, the animals received it orally. In blood serum CH, triglycerides (TG) and HDL cholesterol (HDL-CH). LDL-CH and atherogenic index were calculated by the known formulas by Friedewald and Klimov. Lipoproteins were separated by density gradient ultracentrifugation. Samples of liver, after preliminary extraction of lipids, CH and TG levels were determined. The lipid content was determined by an enzymatic method using a recruitment firm Randox (England). Statistical analysis was performed using the program «Statgraphics». All procedures and animal experiments were carried out in accordance with the «Rules of good laboratory practice in the Russian Federation» (Directive of the European Parliament and the European Union №2010 / 63 / UOM). Rules approved by order of the Ministry of Health of the Russian Federation №267 from 19.06.2003 and approved by the Ethics Committee of the Biomedical Institute of Experimental Medicine. The experiments revealed a distinct lipid-lowering effect of CH-ox, microbial enzyme. Thus, the content of total CH in serum of rats was reduced by 40 %, of guinea pigs by 25 %, of rabbits by 47 %. In all groups of animals increase in HDL-CH levels, reduction, increased at DLP liver CH and TG levels was observed. Besides, the increased ratio and atherogenic LDL fall under the influence of CH-ox. A normalizing effect on the CH-ox disturbed in experimental birefringence spectrum of lipids was found. A well-known drug clofibrate shows much less effective lipid-lowering effect. An antiatherogenic change under the action of CH-ox indicates that this enzyme is very effective not only as a hypolipidemic drug, but also as antiatherosclerotic one. In the fundamental study with several models of DLP we show lipid-lowering effect of the drug microbial cholesterol oxidaze on three kinds of animals.

 

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