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Нарушения метаболизма миокарда на фоне химиотерапевтического лечения, а также возможности их коррекции
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.
Key words: doxorubicin, trimetazidine, cardiotoxicity, metabolism.
Ключевые слова: доксорубицин, триметазидин МВ, кардиотоксичность, метаболизм.
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Key words: doxorubicin, trimetazidine, cardiotoxicity, metabolism.
Полный текст
Список литературы
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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.
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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.
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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.
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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.
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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.
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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
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 Moscow State University of Medicine and Dentistry;
2 14th Korolenko City Clinical Hospital;
3 20th Moscow City Policlinic
*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
________________________________________________
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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