Preview

Cardiovascular Therapy and Prevention

Advanced search

Trimetazidine effects on mitochondria energetic activity

Abstract

Aim. To investigate how trimetazidine (TMZ) directly affects oxidative phosphorylation in intact mitochondria (MCH), isolated from the animals not undergoing ischemia-reperfusion process.

Material and methods. Rat liver MCH were isolated by standard methods. Oxidative and phosphorylating MCH functions were studied by polarigraphic methods. TMZ was used in the concentrations of 10-4 М and 10-5 М.

Results. TMZ in concentrations of 10-4 М and 10-5 М decreased the time of added adenosine diphosphate (ADPH) phosphorylation, reduced the amount of oxygen (O2) necessary for this phosphorylation, and increased ADPH/O2 coefficient. Therefore, phosphorylation velocity and effectiveness increased, i.e. O2 use became more economical, and ATPH synthesis increased. TMZ also increased breath control, which pointed to oxidation and phosphorylation association. TMZ per se did not separate these two processes.

Conclusion. MCH energetic function improvement is one of the key factors in TMZ cytoprotective effects.

About the Authors

S. V. Eliseeva
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


S. V. Grachev
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


N. D. Egorova
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


M. G. Glezer
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


E. I. Astashkin
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


References

1. Harpey C, Clauser P, Labrid C, et al. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Ddrug Rev 1989; 6: 292-312.

2. Renaud JF,. Internal pH, Na+ and Ca2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc drugs Ther 1988; 1(6): 677-86.

3. Cruz C, Zaoui A, Ayoub S, et al. Alterations des myocytes isoles des ventricules de coeur de rat adulte: Protection par la trimetazidine. Concours Med 1987; 36(Suppl): 3470-5.

4. Tsimoyiannis EC, Moutesidou KJ, Moschos CM, et al. Trimetazidine for prevention of hepatic injury induced by ischemia and reperfusion in rats. Eur J Surg 1993; 159: 89-93.

5. Guarnieri C, Muscari C. Effectof trimetazidine on mitochondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium. Pharmacology 1993; 46: 324-31.

6. Elimadi A, Settaf A, Morin D, et al. Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion by preserving mitochondrial function. J Pharmacol Exp Ther 1998;

7. Elimadi A, Morin D, Sapena R, et al. Comparison of the effects of cyclosporine A and trimetazidine on Ca2+-dependent mitochondrial swelling. Fundam Clin Pharmacol 1997; 11: 440-7.

8. Salducci MD, Chauvet-Monges AM, Tillement JP, et al. Trimetazidine reverses calcium accumulation and impairment of phosphorylation induced by cyclosporine A in isolated rat liver mitochondria. J Pharmacol Exp Ther 1996; 277: 417-22.

9. Tillement JP, Crevat A, Testa B, Le Ridant A. Pharmacological modulation of mitochondrial oxidative phosphorylation: inhibition by cyclosporine A, restoration by trimetazidine. Ann Pharm Fr 1996; 54(6): 268-71.

10. Morin D, Elimadi A, Sapena R, et al. Evidence for the existence of [-3H]-trimetazidine binding sites involved in the regulation of the mitochondrial permeability transition pore. Brit J Pharmacol 1998; 123: 1385-94.

11. Morin D, Sapena R, Elimadi A, et al. [3H]-trimetazidine mitochondrial binding sites: regulation by cations, effect of trimetazidine derivatives and other agents and interaction with an endogenous substance. Brit J Pharmacol 2000; 130: 655-63.

12. Schneider WC, Hogeboom GH. Intracellular distribution of enzymes. J Biol Chem 1950; 183: 123.11.

13. Гублер Е.В., Генкин А.А. Применение непараметрических критериев статистики в медико-биологических исследованиях. Ленинград "Медицина" 1973; 141 с: 12.

14. Grynberg A, Demaison L. Fatty acid oxidation in the heart. J Cardiovasc Pharmacol 1996; 28(Suppl 1): Sl 1-7.

15. GrynbergA. Effectors offatty acid oxidation reduction: promising new anti-ischaemic agents. Curr Pharmaceutical Design 2005; 11(4): 489-509.

16. Essop MF, Opie LH. Metabolic therapy for heart failure. Eur Heart J 2004; 25: 1765-8.

17. Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol 2003; 17(2): 133-45.

18. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580-8.

19. Асташкин Е.И., Глезер М.Г. Фармакологическая регуляция обмена энергетических субстратов в кардиомиоцитах при патологических состояниях, связанных с ишемией. Кардиоваск тер профил 2006; 5(7): 112-23.

20. Tabbi-Anneni I, Lucien A, Grynberg A. Trimetazidine effect on phospholipid synthesis in ventricular myocytes: consequence in p-adrenergic dignaling. Fundam Clin Pharmacol 2003; 17: 51-9.

21. Argaud L, Gomez L, Gateau-Roesch O, et al. Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury. J Mol Cell Cardiol 2005; 39(6): 893-9.

22. Morillas Blasco PJ, Hernandiz Martinez A, Azorin Villena I, et al. Mitochondrial changes induced by trimetazidine in the myocardium. Med Sci Monit 2005; 11(6): BR 162-7.

23. Maridonneau-Parini I, Harpey C. Trimetazidine protects the human red blood cell against oxygen free radical damage. Cardiovasc Drugs Ther 1990; 4: 818-9.


Review

For citations:


Eliseeva S.V., Grachev S.V., Egorova N.D., Glezer M.G., Astashkin E.I. Trimetazidine effects on mitochondria energetic activity. Cardiovascular Therapy and Prevention. 2008;7(8):64-69. (In Russ.)

Views: 507


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1728-8800 (Print)
ISSN 2619-0125 (Online)