HYPOLIPIDEMIC EFFECT OF ARGLABIN IN HEPATOMA TISSUE CULTURE
https://doi.org/10.20538/1682-0363-2015-6-75-80
Abstract
Objective. Investigation of hypolipidemic effect of sesquiterpene γ-lactone Arglabin in hepatoma tissue culture (HTC).
Materials and methods. In this study we’ve evaluated the effect of sesquiterpene γ-lactone Arglabin and gemfibrozil (reference drug) on the lipid content in the hepatoma tissue culture (HTC) which were incubated with a fat emulsion “Lipofundin” by fluorescent method with vital dye Nile Red. The cell viability was investigated using the MTT-test and staining by Trypan blue.
Results. Cultivation of cell cultures of rat’s hepatoma cell line HTC with Arglabin and gemfibrozil in concentrations from 10 to 50 μmol and from 0.25 to 0.5 mmol, respectively, had no cytotoxic effect.
HTC cell viability did not change compared with the corresponding rate in the control culture. Experimental hyperlipidemia in hepatoma culture was induced by the addition in the incubation medium
of fat emulsion “Lipofundin” in a final concentration of 0.05 %. The fluorescence intensity of Nile Red in the cells was increased 4-fold (p < 0.05), which indicates a significant accumulation of lipids in the cytosol of cells. In these steady-state Arglabin and gemfibrozil at concentrations 75–100 μM and 0.25–1.0 mM, respectively, reduced the content of lipid in cells.
Conclusion. In the model of hyperlipidemia induced by lipofundin, sesquiterpene γ-lactone Arglabin prevents the accumulation of lipids in the HTC cell line, as evidenced by a decrease in Nile Red fluorescence. However hypolipidemic effect of Arglabin is associated with cytotoxic effects, which is typical for anticancer drugs.
About the Authors
A. V. RatkinRussian Federation
Siberian State Medical University, Tomsk, Russian Federation Ph. +7-903-915-3991, 8 (3822) 90-11-01 (1800)
Yu. A. Pfarger
Russian Federation
Siberian State Medical University, Tomsk, Russian Federation
V. V. Ivanov
Russian Federation
Siberian State Medical University, Tomsk, Russian Federation
S. M. Adekenov
Russian Federation
International Scientific-Industrial Holding “Phytochemistry”, Karaganda, Kazakhstan
O. A. Kaidash
Russian Federation
Siberian State Medical University, Tomsk, Russian Federation
V. S. Chuchalin
Russian Federation
State Medical University, Tomsk, Russian Federation
V. V. Novitsky
Russian Federation
Siberian State Medical University, Tomsk, Russian Federation
References
1. Амосова Е.Н. Гиполипидемическая терапия при ишемической болезни сердца // Укр. кардиол. журн. 2002. Т. 6. С. 13–18.
2. Буеверова Е.Л., Драпкина О.М., Ивашкин В.Т. Атерогенная дислипидемия и печень // Рос. мед. вести. 2008.Т. 13, № 1. С. 17–23.
3. Вайнсон А.А., Мещерикова В.В., Касаткина Н.Н. Изучение радиомодифицирующего действия препарата арглабин при локальном облучении перевивных опухолей и нормальной ткани (кожи) мышей // Рос. биотерапевт. журн. 2005. Т. 4, № 2. С. 32–34.
4. Макаров М.С. Флюоресценция в исследовании клеток: пути и возможности // Молекулярная медицина. 2013. № 4. С. 10–14.
5. Ратькин А.В., Арыстан Л.И., Яковлева Ю.А., Иванов В.В., Рязанцева Н.В., Чучалин В.С., Адекенов С.М. Влияние сесквитерпенового γ-лактона леукомизина на уровень триацилглицеролов в клетках крысиной гепатомы при экспериментальной модели гиперлипидемии // Сиб. мед. обозрение. 2014. Т. 1. С. 44–48.
6. Рахимов К.Д. Фармакологическое и доклиническое изучение нового противоопухолевого препарата арглабин // Рос. биотерапевт. журн. 2005. Т. 4, № 2. С. 15–17.
7. Роднова Е.А., Иванов В.В., Ледюкова С.И., Чучалин В.С., Ратькин А.В., Рахимова Б.Б., Хабаров И.А., Адекенов С.М. Гиполипидемическое действие леукомизина на модели острой гиперлипидемии, индуцированной этанолом // Бюл. сиб. медицины. 2013. Т. 12, № 1. С. 43–48.
8. Chaturvedi D. Sesquiterpene lactones: structural diversity and their biological activities // Research signpost. 2011. P. 313–334.
9. Giri Sh., Nieber K. et al. Telomerase activity and hepatic functions of rat embryonic liver progenitor cell in nanoscaf-fold-coated model bioreactor // Mol. Cell. Biochem. 2010. V. 336. P. 137–149.
10. Ilan E., Tirosh О., Madar Z. Triacylglycerol-mediated oxidative stress inhibits nitric oxide production in rat isolated hepatocytes // J. Nutr. 2005. V. 135, № 9. P. 2090–2095.
11. Kumar D., Parcha V., Maithani A., Dhulia I. Effect and evaluation of antihyperlipidemic activity guided isolated fraction from total methanol extract of Salvadoraoleoides (Decne.) in Triton WR-1339 Induced hyperlipidemic rats // Pharmacogn. Mag. 2012. V. 8, № 32. P. 314–318.
12. Ozansoy G., Akin F.B. Effects of gemfibrozil treatment on vascular reactivity of streptozotocin-diabetic rat aorta // J. Pharm. Pharmacol. 2004. V. 56. P. 241–246.
13. Ramsey S., Gold E.S., Aderem A. A systems biology approach to understanding atherosclerosis // EMBO Mol. Med. 2010. V. 2. P. 79–89.
14. Roche L.D., Medina E.A., Perez A.F. et al. Lipofundin-induced hyperlipidemia promotes oxidative stress and atherosclerotic lesions in New Zealand white rabbits // Int. J. Vasc. Med. 2012. V. 2012. P. 1–7.
15. Shen Ch., Meng Q., Schmelzer E., Bader A. Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity // Toxicol. Appl. Pharmacol. 2009. V. 238. P. 178–187.
16. Umeda Y., Kako Yu., Mizutani K. et al. Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine // The Journal of Lipid Research. 2001. V. 42. P. 1214–1219.
17. Wyrebska A., Gach K., Szemraj J., Szewczyk K., Hrabec E., Koszuk J., Janecki T., Janecka A. Comparison of anti-invasive activity of parthenolide and 3-isopropyl-2-methyl-4-methyleneisoxazolidin-5-one (MZ-6) – a new compound with α-methylene-γ-lactone motif – on two breast cancer cell lines // Chem. Biol. Drug Des. 2013. V. 79. P. 112–120.
18. Wyrebska A., Szymanski J., Gach K., Piekielna J., Koszuk J., Janecki T., Janecka A. Apoptosis-mediated cytotoxic effects of parthenolide and the new synthetic analog MZ-6 on two breast cancer cell lines // Mol. Biol. Rep. 2013. V. 40. P. 1655–1663.
Review
For citations:
Ratkin A.V., Pfarger Yu.A., Ivanov V.V., Adekenov S.M., Kaidash O.A., Chuchalin V.S., Novitsky V.V. HYPOLIPIDEMIC EFFECT OF ARGLABIN IN HEPATOMA TISSUE CULTURE. Bulletin of Siberian Medicine. 2015;14(6):75-80. (In Russ.) https://doi.org/10.20538/1682-0363-2015-6-75-80