rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2010-6-4-481-484rpcardio-844Research ArticleORIGINAL STUDIESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯEFFICACY OF VARIOUS DRUG FORMS OF LYCOPENE IN PATIENTS WITH DYSLIPIDEMIAЭФФЕКТИВНОСТЬ РАЗЛИЧНЫХ ЛЕКАРСТВЕННЫХ ФОРМ ЛИКОПИНА У ПАЦИЕНТОВ С ДИСЛИПИДЕМИЯМИДовгалевскийП. Я.DovgalevskyP. Ya.

д.м.н., профессор, директор

410028, Саратов, ул. Чернышевского, 141 

Chernyshevskogo ul. 141, Saratov, 410028

КлочковВ. А.KlochkovV. A.

д.м.н., профессор, заведующий лабораторией 

410028, Саратов, ул. Чернышевского, 141 

Chernyshevskogo ul. 141, Saratov, 410028

v-klochkov1@yandex.ruЧалыкН. Е.ChalykN. E.

к.б.н., ученый секретарь 

410028, Саратов, ул. Чернышевского, 141 

Chernyshevskogo ul. 141, Saratov, 410028

АнсимоваО. М.AnsimovaO. M.

заведующая лабораторией биохимии 

410028, Саратов, ул. Чернышевского, 141 

Chernyshevskogo ul. 141, Saratov, 410028

PetyaevI.PetyaevI.

медицинский директор 

Hauser Forum, 3 Charles Babbage Road, Cambridge CBO OGT

Hauser Forum, 3 Charles Babbage Road, Cambridge CBO OGT, UK

Саратовский научно-исследовательский институт кардиологииРоссияSaratov Research Institute of CardiologyRussian FederationCambridge Theranostics Ltd., Кембриджский университетВеликобританияCambridge Theranostics Ltd., University of CambridgeUnited Kingdom20101801201664481484Copyright © Dovgalevsky P.Y., Klochkov V.A., Chalyk N.E., Ansimova O.M., Petyaev I., 20162016Довгалевский П.Я., Клочков В.А., Чалык Н.Е., Ансимова О.М., Petyaev I.Dovgalevsky P.Y., Klochkov V.A., Chalyk N.E., Ansimova O.M., Petyaev I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/844Aim

Aim. To find the optimal scheme of lycopene application and to compare clinical efficacy of two lycopene presentations produced on the basis of 1) vegetable oil and 2) milk protein (lactolycopene) in patients with dyslipidemia.

Material and methods

Material and methods. At the first step of the study to choice an optimal scheme of pharmacotherapy efficacy of three schemes of lycopene (lactolycopene) application was compared in three groups of patients (n= 27, 25 and 28 respectively) with ischemic heart disease, dyslipidemia and high level of lipid peroxygenation (LPO). At the second step two groups of patients (n=28 and 31) with dyslipidemia received lycopene in the same dose at the same time but in different presentations. Patients of the first group received oil solution of lycopene in capsules, patients of the second group — a powder of lactolycopene dissolved in 100 ml of boiled water. Levels of total cholesterol (TC), high density (HDC) and low density cholesterol (LDC), triglycerides (TG) and LPO activity marker, malondialdehyde (MDA), were studied. The duration of each study step was 8 weeks.

Results

Results. Lactolycopene 10 mg QD for the night was as effective as 10 mg TID (30 mg per day) in normalization of the lipid metabolism parameters and malondialdehyde level due to chronopharmacological mechanism. Similar efficacy of the evening lactolycopene reception 10 mg QD and 30 mg QD was due to the saturation of tissues with an antioxidant. Lactolycopene application led to significant reduction in levels of TC (from 247.1±27 to 186.5±12 mg/dl; p<0.001), LDC (from 150.9±17 to 119.3±8 mg/dl; p<0.001), TG (from 165.8±12 to 128±10 mg/dl; p<0.001) and MDA (from 2.67±0.2 to 1.3±0.07 nM/ml; p<0.001) unlike reception of oil solution of lycopene.

Conclusion

Conclusion: Lactolycopene has higher effect on lipid metabolism and LPO in comparison with this in lycopene in oil solution presentation. An optimal scheme of lactolycopene reception is 10 mg for the night.

Цель

Цель. Отработка оптимальной схемы приема ликопина и сравнение клинической эффективности двух его лекарственных форм произведенных на основе 1) растительных жиров и 2) молочного протеина (лактоликопина), у пациентов с дислипидемиями.

Материал и методы

Материал и методы. На первом этапе для выбора схемы фармакотерапии сравнивали эффективность трех схем приема ликопина (лактоликопина) у пациентов трех групп (n=27, 25 и 28, соответственно) с ишемической болезнью сердца, дислипидемией и повышенным уровнем перекисного окисления липидов (ПОЛ). На втором этапе из 59 больных с дислипидемиями были сформированы две группы, получавшие терапию ликопином в равной дозе в одинаковое время. Больные первой группы (n=28) получали масляный раствор ликопина в капсулах, больные второй группы (n=31) — взвесь порошка лактоликопина, разведенного в 100 мл кипяченой воды. Исследовали уровни общего холестерина (ОХС), холестерина липопротеинов высокой (Хс ЛВП) и низкой плотности (Хс ЛНП), триглицеридов (ТГ) и показателя ПОЛ — малонового диальдегида (МДА). Длительность каждого из этапов исследования была 8 нед.

Результаты

Результаты. Лечение лактоликопином в суточной дозе 10 мг однократно на ночь нормализует показатели липидного обмена и уровня малонового диальдегида так же эффективно, как и трехкратный прием в течение дня 10 мг (или 30 мг/сут), за счет хронофармакологического механизма. Одинаковая эффективность была характерна для вечернего приема лактоликопина в дозах 10 и 30 мг за счет «насыщения» тканей антиоксидантом. Применение лактоликопина привело к значимому снижению уровней ОХС (с 247,1±27 до 186,5±12 мг/дл; p<0,001), Хс ЛНП (с 150,9±17 до 119,3±8 мг/дл; p<0,001), ТГ (с 165,8±12 до 128±10 мг/дл; p<0,001) и МДА (с 2,67±0,2 до 1,3±0,07 нМ/мл; p<0,001) в отличие от приема ликопина на масляной основе.

Заключение

Заключение. Эффективность влияния лактоликопина на липидный обмен и процессы ПОЛ выше, чем препарата на масляной основе, оптимальный режим его приема 10 мг вечером.

антиоксидантыбиодоступностьлекарственные формыдислипидемияantioxidantsbioavailabilitydrug presentationdyslipidemiaReferencesVerhoye E., Langlois M.R.; Asklepios Investigators. Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk? Clin Chem Lab Med 2009; 47(2): 128-137.Verhoye E., Langlois M.R.; Asklepios Investigators. Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk? Clin Chem Lab Med 2009; 47(2): 128-137.Gieseg S.P., Leake D.S., Flavall E.M. et al. Macrophage antioxidant protection within atherosclerotic plaques. Front Biosci 2009; 14: 1230-46.Gieseg S.P., Leake D.S., Flavall E.M. et al. Macrophage antioxidant protection within atherosclerotic plaques. Front Biosci 2009; 14: 1230-46.Vivekananthan D.P., Penn M.S., Sapp S.K. et al. Use of antioxidant vitamins forthe prevention of cardiovascular disease: meta-analysis ofrandomised trials. Lancet 2003;361(9374):2017-23.Vivekananthan D.P., Penn M.S., Sapp S.K. et al. Use of antioxidant vitamins forthe prevention of cardiovascular disease: meta-analysis ofrandomised trials. Lancet 2003;361(9374):2017-23.Brown B.G., Cheung M.C., Lee A.C. et al. Antioxidant vitamins and lipid therapy: end of a long romance? Arterioscler Thromb Vasc Biol 2002;22(10):1535-46.Brown B.G., Cheung M.C., Lee A.C. et al. Antioxidant vitamins and lipid therapy: end of a long romance? Arterioscler Thromb Vasc Biol 2002;22(10):1535-46.Hung C.F., Huang T.F., Chen B.H. et al. Lycopene inhibits TNF-alpha-in￾duced endothelial ICAM-1 expression and monocyte-endothelial adhesion. Eur J Pharmacol 2008; 586(1-3): 275-82.Hung C.F., Huang T.F., Chen B.H. et al. Lycopene inhibits TNF-alpha-in￾duced endothelial ICAM-1 expression and monocyte-endothelial adhesion. Eur J Pharmacol 2008; 586(1-3): 275-82.Napolitano M., De Pascale C., Wheeler-Jones C. et al. Effects of lycopene on the induction offoam cellformation by modified LDL.Am J Physiol Endocrinol Metab 2007;293(6):E1820-7.Napolitano M., De Pascale C., Wheeler-Jones C. et al. Effects of lycopene on the induction offoam cellformation by modified LDL.Am J Physiol Endocrinol Metab 2007;293(6):E1820-7.Hu M.Y., Li Y.L., Jiang C.H. et al. Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits. Nutrition 2008; 24(10): 1030-38.Hu M.Y., Li Y.L., Jiang C.H. et al. Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits. Nutrition 2008; 24(10): 1030-38.Sofi F., Abbate R., Gensini G.F., Casini A. Evidences on the relationship between Mediterranean diet and health status. Recenti Prog Med 2009; 100(3): 127-31Sofi F., Abbate R., Gensini G.F., Casini A. Evidences on the relationship between Mediterranean diet and health status. Recenti Prog Med 2009; 100(3): 127-31Murr C., Winklhofer-Roob B.M., Schroecksnadel K. et al. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 2009;202(2):543-9.Murr C., Winklhofer-Roob B.M., Schroecksnadel K. et al. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 2009;202(2):543-9.Rowley K., Walker K.Z., Cohen J. et al. Inflammation and vascular endothelial activation in anAboriginal population: relationships to coronary disease risk factors and nutritional markers. Med J Aust 2003;178(10):495-500.Rowley K., Walker K.Z., Cohen J. et al. Inflammation and vascular endothelial activation in anAboriginal population: relationships to coronary disease risk factors and nutritional markers. Med J Aust 2003;178(10):495-500.Miller E.R. 3rd, Pastor-Barriuso R., Dalal D. et al. Meta-analysis: highdosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142(1):37-46.Miller E.R. 3rd, Pastor-Barriuso R., Dalal D. et al. Meta-analysis: highdosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142(1):37-46.van Het Hof K.H., West C.E., Weststrate J.A., HautvastJ.G. Dietary factors that affect the bioavailability of carotenoids. J Nutr 2000;130(3):503-6.van Het Hof K.H., West C.E., Weststrate J.A., HautvastJ.G. Dietary factors that affect the bioavailability of carotenoids. J Nutr 2000;130(3):503-6.Unlu N.Z., Bohn T., FrancisD.M. et al. Lycopene from heat-induced cisisomer-rich tomato sauce is more bioavailable than from all-trans-rich tomato sauce in human subjects. Br J Nutr 2007;98(1): 140-6.Unlu N.Z., Bohn T., FrancisD.M. et al. Lycopene from heat-induced cisisomer-rich tomato sauce is more bioavailable than from all-trans-rich tomato sauce in human subjects. Br J Nutr 2007;98(1): 140-6.B hm V., Bitsch R. Intestinal absorption of lycopene from different matrices and interactions to other carotenoids, the lipid status, and the antioxidant capacity of human plasma. Eur J Nutr 1999;38(3):118-25.B hm V., Bitsch R. Intestinal absorption of lycopene from different matrices and interactions to other carotenoids, the lipid status, and the antioxidant capacity of human plasma. Eur J Nutr 1999;38(3):118-25.NguyenM.L., Schwartz S.J. Lycopene: chemical and biological properties. Food Tech 1999; 53(2): 38–45.NguyenM.L., Schwartz S.J. Lycopene: chemical and biological properties. Food Tech 1999; 53(2): 38–45.Mellert W., Deckardt K., Gembardt C. et al. Thirteen-week oral toxicity study of synthetic lycopene products in rats. Food Chem Toxicol 2002;40(11):1581-8.Mellert W., Deckardt K., Gembardt C. et al. Thirteen-week oral toxicity study of synthetic lycopene products in rats. Food Chem Toxicol 2002;40(11):1581-8.Shao A., Hathcock J.N. Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol 2006;45(3):289-98.Shao A., Hathcock J.N. Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol 2006;45(3):289-98.Richelle M., Bortlik K., Liardet S. et al. A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. J Nutr 2002;132(3):404-8.Richelle M., Bortlik K., Liardet S. et al. A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. J Nutr 2002;132(3):404-8.EdwardsA.J., Vinyard B.T., Wiley E.R. et al. Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans. J Nutr 2003;133(4):1043-50.EdwardsA.J., Vinyard B.T., Wiley E.R. et al. Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans. J Nutr 2003;133(4):1043-50.Aust O., Stahl W., Sies H. et al. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005;75(1):54-60.Aust O., Stahl W., Sies H. et al. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005;75(1):54-60.Bunker C.H., McDonald A.C., Evans R.W. et al. A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Nutr Cancer 2007;57(2):130-7.Bunker C.H., McDonald A.C., Evans R.W. et al. A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Nutr Cancer 2007;57(2):130-7.Parker T.S., McNamara D.J., Brown C. et al. Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man. Proc Natl Acad Sci U S A 1982;79(9): 3037-41.Parker T.S., McNamara D.J., Brown C. et al. Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man. Proc Natl Acad Sci U S A 1982;79(9): 3037-41.

The authors declare that there are no conflicts of interest present.