EFFECTS OF LUDARTIN AND LEUKOMISIN ON THE ACUTE HYPERLIPIDEMIA MODEL INDUCED BY ETHANOL

Objective: study sesquiterpene lactones ludartin and leukomisin lipid-lowering properties on the model of acute hyperlipidemia induced by ethanol in rats.

Material and methods. Rats during 7 days injected into the stomach ludartin and leukomisin in a dose 10 mg/kg or reference drug nicotinic acid in a dose 25 mg/kg. Hyperlipidemia caused by single introduc-tion of ethanol into the stomach in a dose 5 g/kg. In blood serum of tail vein measured the triacylgly-cerols, total cholesterol, high density and low density lipoproteins cholesterol, also the level of free fatty acids. Calculated the ratio of high density lipoproteins cholesterol to the amount of low density lipopro-teins cholesterol and the index of atherogenicity.

Results. A single dose of ethanol increased serum level of triacylglycerols in 1.9 times, free fatty acids – in 3.2 times, low density lipoproteins – on 44% in comparison with the intact animals indices. It shows the development of acute hyperlipidemia. Serum total cholesterol, high density lipoproteins cholesterol and the index of atherogenicity were not changed. Course introduction of sesquiterpene lactones ludartin and leukomisin against the background of acute hyperlipidemia was accompanied by a decrease in the serum of triacylglycerols levels respectively by 37.5% and 49.5%. Nicotinic acid lowered the content of triacylglycerols by 42.4%. Ludartin, leukomisin and nicotinic acid reduced the increased level of free fatty acids in the blood serum by 63.4%, 41.6% and 67.9%. Ludartin, leukomisin and nicotinic acid de-creased by 15.8%, 20.3% and 17.2% of total cholesterol in the blood serum. In acute hyperlipidemia ludartin and leukomisin reduced low density lipoproteins cholesterol by 23.8% and 14.8%, respectively, nicotinic acid – by 15.7%. Both of sesquiterpene lactone and nicotinic acid did not modify the content of high density lipoproteins cholesterol. When introduction ludartin and nicotinic acid ratio of high density lipoproteins cholesterol to the amount of low density lipoproteins cholesterol significantly increased by 32.7% and 22.1% respectively.

Conclusion. Sesquiterpene lactones ludartin and leukomisin posses hypolipidemic effect in acute experi-mental hyperlipidemia caused by the ethanol introduction. Lactones normalize many indices of lipid me-tabolism, which can be caused by different biochemical targets of these molecules. Lactones, as nicotinic acid, in the model of acute hyperlipidemia decrease in blood serum triacylglycerols, total cholesterol, and low density lipoproteins cholesterol content. 

1. Atherosclerosis – Diet-induce atherosclerosis/hyperchole-sterolemia in rodent models. Ed. by M.A. Pellizzon. URL: http://www.researchdiets.com/product-literature

2. Vander Laan P.A., Reardon С.А. The unusual suspects: an overview of the minor leucocyte populations in atherosclerosis. J. Lipid Res., 2005, vol. 46, no. 7, pp. 829–838.

3. Bueverova Ye.L., Drapkina O.M., Ivashkin V.T. Aterogennaya dislipidemiya i pechen' [Atherogenous dyslipidemia and liver]. Rossiyskie medicinskie vesti – The Russian Medical Vesti, 2008, vol. 13, no. 1, pp. 17–23 (in Russian).

4. Hansson G.K., Robertson A.-K.L., Soderberg-Naucler C. Inflammation and atherosclerosis. Annu. Rev. Pathol. Mech. Dis., 2006, vol. 1, no. 2, pp. 297–329.

5. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 2001, vol. 285, no. 12, pp. 2486–2497.

6. Vasilenko Yu.K., Lisevitskaya L.I., Frolova L.M., Parfentieva E.P., Skulte I.V., Vasilenko A.Yu., Kozharsky V.V., Voskanyan V.L. Chem.-Farm. J., 1982, vol. 45, no. 5, pp. 66–70 (in Russian).

7. Shimoda H., Ninomiya K., Nishida N. et al. Anti-hyper-lipidemic sesquiterpenes and new sesquiterpene glycosides from the leaves of artichoke (Cynara scolymus L.): structure requirement and mode of action. Bioorg. Med. Chem. Lett., 2003, vol. 13, no. 2, pp. 223–228.

8. Eliza J., Daisy P., Ignacimuthu S., Duraipandiyan V. Antidiabetic and antilipidemic effect of eremanthin from Costus speciosus (Koen.) Sm., in STZ-induced diabetic rats. Chem. Biol. Interact., 2009, vol. 182, no. 1, pp. 67–72.

9. Kim S.H., Park K.S. Effects of Panax ginseng extract on li-pid metabolism in humans. Pharmacol. Res., 2003, vol. 48, no. 5, pp. 511–513.

10. Hennekens C.H. Current perspectives on lipid lowering with statins to decrease risk of cardiovascular disease. Clin. Cardiol., 2001, vol. 24, no. 7, pp. 2–5.

11. Kagarlitskiy A.D., Adekenov S.M., Kupriyanov A.N. Seskviterpenovye laktony rasteniy Central'nogo Kazahstana

12. [Sesquiterpene lactones of plants in Central Kazakhstan]. Alma-Ata, Nauka Publ., 1987. 240 p. (in Russian).

13. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv. Ch. 1. Ed. by A.I. Mironov [Guide-lines for pre-clinical trials of drugs. Part 1]. Moscow, Grif and Co Publ., 2013. 944 p. (in Russian).

14. Sapronov N.S., Khnychenko L.K., Okunevich I.V., Gavrovskaya L.K. Potential antiatherosclerotic drugs: novel N-substituted taurinamide derivatives. Adv. Exp. Med. Biol., 2006, vol. 583, pp. 515–521.

15. Bodor E.T., Offermanns S. Nicotinic acid: an old drug with a promising future. Br. J. Pharmacol., 2008, vol. 153, no. 1, pp. 68–75.

16. Ren N., Kaplan R., Hernandez M. et al. Phenolic acids sup-press adipocyte lypolisis via activation of the nicotinic acid receptor GRP109A (HM74a/PUMA-G). J. Lipid Res., 2011, vol. 50, no. 5, pp. 908–914.