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Нарушения метаболизма миокарда на фоне химиотерапевтического лечения, а также возможности их коррекции
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Аннотация
В последние годы отмечается значительный прогресс в лечении целого ряда онкологических заболеваний, связанный с разработкой новых химиотерапевтических препаратов. Как правило, они применяются в комбинации с классическими режимами химиотерапии, включающими доксорубицин. На фоне такого комбинированного лечения отмечено значимое увеличение продолжительности жизни пациентов, однако в то же время существенно возрастает риск кардиотоксического действия. В обзоре приведены сведения о нарушениях метаболизма кардиомиоцитов на фоне терапии антрациклинами, обсуждаются возможности патогенетического лечения и профилактики.
Ключевые слова: доксорубицин, триметазидин МВ, кардиотоксичность, метаболизм.
Ключевые слова: доксорубицин, триметазидин МВ, кардиотоксичность, метаболизм.
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Recent years have seen significant progress in the treatment of many oncologicaldiseases associated with the development of new chemotherapeutic agents. Typically, they are used in combination with classical chemotherapy regimens that include doxorubicin. In the background of this combined treatment significant prolongation of life of the patients was noted, but at the same time the risk of cardiotoxicity was considerably increased. The survey provides information about the cardiomyocytesmetabolic disorders during therapy with anthracyclines, discussing the possibility of pathogenetic treatment and prevention.
Key words: doxorubicin, trimetazidine, cardiotoxicity, metabolism.
Полный текст
Список литературы
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32. Li YJ, Wang PH, Chen C et al. Improvement of mechanical heart function by trimetazidine in db/db mice. Acta Pharmacol Sin 2010; 31 (5): 560–9.
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35. Ватутин Н.Т., Калинкина Н.В., Риджок В.В., Столика О.И. Влияние триметазидина на вариабельность сердечного ритма и систолическую функцию левого желудочка у пациентов, получающих антрациклиновые антибиотики. Кровообігта гемостаз. 2005; 3–4: 141–5.
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37. Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight Nature Reviews Cancer/AOP 2013; doi:10.1038/nrc3483
2. Swain S, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003; 97: 2869–79.
3. Mercuro G, Cadeddu C, Piras A et al. Early epirubicin-induced myocardial dysfunction revealed by serial tissue doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist 2007; 12: 1124–33.
4. Von Hoff DD, Layard MW, Basa P et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91: 710–7.
5. Minotti G, Menna P, Salvatorelli E et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56: 185–229.
6. Tokarska-Schlattner M, Wallimann T, Schlattner U. Alterations in myocardial energy metabolism induced by the anti-cancer drug doxorubicin. C R Biol 2006; 329 (9): 657–68.
7. Jeyaseelan R, Poizat C, Wu HY, Kedes L. Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes is associated with ATP depletion in rat cardiomyocytes. J Biol Chem 1997; 272: 5828–32.
8. Pelikan PC, Weisfeldt ML, Jacobus WE et al. Acute doxorubicin cardiotoxicity: functional, metabolic, and morphologic alterations in the isolated, perfused rat heart. J Cardiovasc Pharmacol 1986; 8: 1058–66.
9. Nicolay K, Aue WP, Seelig J et al. Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31PNMR and implications for adriamycin-induced cardiotoxicity. Biochim Biophys Acta 1987; 929: 5–13.
10. Eidenschink AB, Schroter G, Muller-Weihrich S, Stern H. Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in childhood. Cardiol Young 2000; 10: 610–7.
11. Praet M, Ruysschaert JM. In-vivo and in-vitro mitochondrial membrane damages induced in mice by adriamycin and derivatives. Biochim Biophys Acta 1993; 1149: 79–85.
12. Nony P, Guastalla J-P, Rebattu P et al. In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy. Cancer Chemother Pharmacol 2000; 45: 375–80.
13. Muraoka S, Miura T. Inactivation of mitochondrial succinatedehydrogenase by adriamycin activated by horseradish peroxidase and hydrogen peroxide. Chem Biol Interact 2003; 145: 67–75.
14. Zhou S, Starkov A, Froberg MK et al. Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Cancer Res 2001; 61: 771–7.
15. Lopaschuk GD, Belke DD, Gamble J et al. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochim Biophys Acta 1994; 1213: 263–76.
16. Bordoni A, Biagi P, Hrelia S. The impairment of essential fatty acid metabolism as a key factor in doxorubicin-induced damage in cultured rat cardiomyocytes. Biochim Biophys Acta 1999; 1440: 100–6.
17. Hong YM, Kim HS, Yoon HR. Serum lipid and fatty acid profiles in adriamycin-treated rats after administration of L-carnitine. Pediatr Res 2002; 51: 249–55.
18. Wakasugi S, Fischman AJ, Babich JW et al. Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy. J Nucl Med 1993; 34: 1529–35.
19. Hrelia S, Fiorentini D, Maraldi T et al. Doxorubicin induces early lipid peroxidation associated with changes in glucose transport in cultured cardiomyocytes. Biochim Biophys Acta 2002; 1567: 150–6.
20. Tokarska-Schlattner M, Wallimann T, Schlattner U. Multiple interference of anthracyclines with mitochondrial creatine kinases: preferential damage of the cardiac isoenzyme and its implications for drug cardiotoxicity. Mol Pharmacol 2002; 61: 516–23.
21. Taegtmeyer H. Metabolism – the lost child of cardiology. J Am Coll Cardiol 2000; 36: 1386–8.
22. Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure J Physiol 2003; 555 (1): 1–13.
23. Schaper J, Froede R, Hein St et al. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 1991; 83: 504–14.
24. Sabbah HN, Sharov V, Riddle JM et al. Mitochondrial abnormalities in myocardium of dogs with chronic heart failure. J Mol Cell Cardiol 1992; 24: 1333–47.
25. De Sousa E, Veksler V, Minajeva A et al. Subcellular creatine kinase alterations – Implications in heart failure. Circ Res 1999; 85: 68–76.
26. Lopaschuk GD, Barr R, Thomas PD, Dyck JR. Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme a thiolase. Circ Res 2003; 93 (3): e33–7.
27. Lopaschuk GD, Kozak R. Trimetazidine inhibits fatty acid oxidation in the heart. J Mol Cell Cardiol 1998; 30: A112–A113.
28. Хадзегова А.Б., Васюк Ю.А., Ющук Е.Н. и др. Возможности миокардиальной цитопротекции в комплексном лечении больных с хронической сердечной недостаточностью. Кардиология. 2006; 11: 48–56.
29. Gao D, Ning N, Niu X et al. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart 2011; 97 (4): 278–86.
30. Zhang L, Lu Y, Jiang H et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J Am Coll Cardiol 2012; 59 (10): 913–22.
31. Amal Mohamed Moustafa Y, Amany Abd-Elrahman M. Shalahy impact of trimetazidine on doxorubicin-induced acute cardiotoxicity in mice:a biochemical and electron microscopic study. Egyptian J Histology 2006; 29 (1): 125–36.
32. Li YJ, Wang PH, Chen C et al. Improvement of mechanical heart function by trimetazidine in db/db mice. Acta Pharmacol Sin 2010; 31 (5): 560–9.
33. Pascale C, Fornengo P, Epifani G et al. Cardioprotection of trimetazidine and anthracycline-induced acute cardiotoxic effects. Lancet 2002; 359: 1153–4.
34. Калинкина Н.В. Влияние триметазидина на безболевую ишемию миокарда и диастолическую функцию левого желудочка у пациентов, получающих антрациклиновые антибиотики. Вестн. неотложной и восстановительной медицины. 2006; 2: 195–8.
35. Ватутин Н.Т., Калинкина Н.В., Риджок В.В., Столика О.И. Влияние триметазидина на вариабельность сердечного ритма и систолическую функцию левого желудочка у пациентов, получающих антрациклиновые антибиотики. Кровообігта гемостаз. 2005; 3–4: 141–5.
36. Tallarico D, Rizzo V, Di Maio F. Myocardial cytoprotection by trimetazidine against anthracycline-induced cardiotoxicity in anticancer chemotherapy Angiology 2003; 54 (2): 219–2.
37. Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight Nature Reviews Cancer/AOP 2013; doi:10.1038/nrc3483
Авторы
Ю.А.Васюк1, Е.Л.Школьник*1, В.В.Несветов1, Л.Д.Школьник2, Г.В.Варлан2, А.В.Пильщиков3
1 ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России;
2 ГБУЗ Городская клиническая больница №14 им. В.Г.Короленко Департамента здравоохранения г. Москвы
3 ГП № 20 г. Москвы
*eshkolnik@mail.ru
1 ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России;
2 ГБУЗ Городская клиническая больница №14 им. В.Г.Короленко Департамента здравоохранения г. Москвы
3 ГП № 20 г. Москвы
*eshkolnik@mail.ru
________________________________________________
Yu.A.Vasyuk1, E.L.Shkolnik*1, V.V.Nesvetov1, L.D.Shkolnik2, G.V.Varlan2, A.V.Pilschikov3
1 Moscow State University of Medicine and Dentistry;
2 14th Korolenko City Clinical Hospital;
3 20th Moscow City Policlinic
*eshkolnik@mail.ru
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