Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction

Journal of Cardiovascular Pharmacology

Volumn 48, Issue 6, 2006, Pages 314-319

  Liepinsh, Edgars ^a   Vilskersts, Reinis ^a   Loca, Dagnija ^a   Kirjanova, Olga ^a   Pugovichs, Osvalds ^a   Kalvinsh, Ivars ^a   Dambrova, Maija ^a  

^a LATVIAN INSTITUTE OF ORGANIC SYNTHESIS   (Latvia)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN ENZYME; CARNITINE; GAMMA BUTYROBETAINE; HEART ENZYME; MILDRONATE;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME BLOOD LEVEL; HEART INFARCTION; HEART MUSCLE NECROSIS; HEART PROTECTION; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; STATISTICAL SIGNIFICANCE;

ANIMALS; BETAINE; CARDIOVASCULAR AGENTS; CARNITINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CORONARY CIRCULATION; GAMMA-BUTYROBETAINE DIOXYGENASE; INJECTIONS, INTRAPERITONEAL; MALE; METHYLHYDRAZINES; MYOCARDIAL INFARCTION; MYOCARDIUM; RATS; RATS, WISTAR;

EID: 33846117009     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.fjc.0000250077.07702.23     Document Type: Article

References (20)

1. Simkhovich BZ, Shutenko ZV, Meirena DV, et al. 3-(2,2,2- Trimethylhydrazinium) propionate (THP)-a novel gamma-butyrobetaine hydroxylase inhibitor with cardioprotective properties. Biochem Pharmacol. 1988;37:195-202.
2. Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr. 1998;18:39-61.
3. Bieber LL. Carnitine. Annu Rev Biochem. 1988;57:261-283.
4. Bremer J. Carnitine-metabolism and functions. Physiol Rev. 1983;63:1420-1480.
5. Asaka N, Muranaka Y, Kirimoto T, et al. Cardioprotective profile of MET-88, an inhibitor of carnitine synthesis, and insulin during hypoxia in isolated perfused rat hearts. Fundam Clin Pharmacol. 1998;12:158-163.
6. Kirimoto T, Nobori K, Asaka N, et al. Beneficial effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on energy metabolism in ischemic dog hearts. Arch Int Pharmacodyn Ther. 1996;331:163-178.
7. Sesti C, Simkhovich BZ, Kalvinsh I, et al. Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics. J Cardiovasc Pharmacol. 2006;47:493-499.
8. Oey NA, van VN, Wijburg FA, et al. L-carnitine is synthesized in the human fetal-placental unit: potential roles in placental and fetal metabolism. Placenta. 2006;27:841-846.
9. Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals. Biochem J. 2002;361:417-429.
10. Akahira M, Hara A, Abiko Y. Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart. Fundam Clin Pharmacol. 1997;11:356-364.
11. Longo A, Bruno G, Curti S, et al. Determination of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivatization with 1-aminoanthracene. J Chromatogr B Biomed Appl. 1996;686:129-139.
12. Hayashi Y, Muranaka Y, Kirimoto T, et al. Effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on tissue carnitine and lipid levels in rats. Biol Pharm Bull. 2000;23:770-773.
13. Yonekura K, Eto Y, Yokoyama I, et al. Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction. Basic Res Cardiol. 2000;95:343-348.
14. Spaniol M, Brooks H, Auer L, et al. Development and characterization of an animal model of carnitine deficiency. Eur J Biochem. 2001;268:1876-1887.
15. Kuwajima M, Harashima H, Hayashi M, et al. Pharmacokinetic analysis of the cardioprotective effect of 3-(2,2,2-trimethylhydrazinium)propionate in mice: inhibition of carnitine transport in kidney. J Pharmacol Exp Ther. 1999;289:93-102.
16. Dambrova M, Liepinsh E, Kalvinsh I. Mildronate: cardioprotective action through carnitine-lowering effect. Trends Cardiovasc Med. 2002;12:275-279.
17. Hosein EA, PROULX P. Isolation and probable functions of betaine esters in brain metabolism. Nature. 1960;187:321-322.
18. Hosein EA, Koh TY. Acetylcholine-like activity of acetyl-L-carnityl CoA in subcellular particles of narcotized brain homogenates. Arch Biochem Biophys. 1966;114:94-101.
19. Hosein EA, Booth SJ, Gasoi I, et al. Neuromuscular blocking activity and other pharmacologic properties of various carnitine derivatives. J Pharmacol Exp Ther. 1967;156:565-572.
20. Dambrova M, Chlopicki S, Liepinsh E, et al. The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation. Naunyn Schmiedebergs Arch Pharmacol. 2004;369:533-539.