Effects of valproic acid on cardiac metabolism

Canadian Journal of Physiology and Pharmacology

Volumn 82, Issue 10, 2004, Pages 927-933

  Daniels, Thomas ^a,b   Gallagher, Maureen ^a,c   Tremblay, George ^a   Rodgers, Robert L ^a  

^a UNIVERSITY OF RHODE ISLAND   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

^c PFIZER INC   (United States)

Author keywords

Butyrate; Glucose; Lactate; Medium chain acyl CoA ligase; Metabolism; Myocardial; Octanoate; Palmitate; Pyruvate

Indexed keywords

ANTICONVULSIVE AGENT; BUTYRIC ACID; CARBOHYDRATE; CARBON 14; CARBON DIOXIDE; FATTY ACID; GLUCOSE; LACTIC ACID; LONG CHAIN FATTY ACID COENZYME A LIGASE; OCTANOIC ACID; PALMITIC ACID; PYRUVIC ACID; TRITIUM; TRITIUM OXIDE; UNCLASSIFIED DRUG; VALPROIC ACID; VALPROYL COENZYME A LIGASE;

ADOLESCENT; ANIMAL TISSUE; CELL FREE SYSTEM; CONFERENCE PAPER; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; ERYTHROCYTE; FATTY ACID OXIDATION; GLUCOSE OXIDATION; HEART MUSCLE METABOLISM; MALE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RAT; TISSUE HOMOGENATE;

ANIMALS; ENERGY METABOLISM; HEART; MALE; MYOCARDIUM; OXIDATION-REDUCTION; RATS; RATS, SPRAGUE-DAWLEY; VALPROIC ACID;

EID: 13544255562     PISSN: 00084212     EISSN: None     Source Type: Journal    
DOI: 10.1139/y04-096     Document Type: Conference Paper

References (48)

1. Adkison, K.D., and Shen, D.D. 1996. Uptake of valproic acid into rat brain is mediated by a medium-chain fatty acid transporter. J. Pharmacol. Exp. Ther. 276: 1189-1200.
2. Baldwin, G.S., Abbott, F.S., and Nau, H. 1996. Binding of valproate metabolite to the trifunctional protein of fatty acid oxidation. FEBS Lett. 384: 58-60.
3. Becker, C.M., and Harris, R.A. 1983. Influence of valproic acid on hepatic carbohydrate and lipid metabolism. Arch. Biochem. Biophys. 223: 381-392.
4. Bolanos, J.P., and Medina, J.M. 1997. Effect of valproate on the metabolism of the central nervous system. Life Sci. 60: 1933-1942.
5. Bonen, A. 2000. Lactate transporters (MCT proteins) in heart and skeletal muscles. Med. Sci. Sports Exercise, 32: 778-789.
6. Bratton, S.L., Garden, A.L., Bohan, T.P., French, J.W., and Clark, W.R. 1992. A child with valproate-associated carnitine deficiency and carnitine-responsive cardiac dysfunction. J. Child Neurol. 7: 413-416.
7. Camina, M.F., Rozas, I., Gomez, M., Paz, J.M., Alonso, C., and Rodriguez-Segade, S. 1991. Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues. Br. J. Pharmacol. 103: 1179-1183.
8. Chadwick, D.W. 1985. Concentration-effect relationships of valproic acid. Clin. Pharmacokinet. 10: 155-163.
9. Coude, F.X., Grimber, G., Pelet, A., and Benoit, Y. 1983. Action of the antiepileptic drug, valproic acid, on fatty acid oxidation in isolated rat hepatocytes. Biochem. Biophys. Res. Commun. 115: 730-736.
10. Coulter, D.L. 1991. Carnitine, valproate, and toxicity. J. Child Neurol. 6: 7-14.
11. Cramer, J.A., and Mattson, R.H. 1979. Valproic acid: in vitro plasma protein binding and interaction with phenytoin. Ther. Drug Monit. 1: 105-116.
12. Draye, J.P., and Vamecq, J. 1987. The inhibition by valproic acid of the mitochondrial oxidation of monocarboxylic and omega-hydroxymonocarboxylic acids: possible implications for the metabolism of gamma-aminobutryric acid. J. Biochem. (Tokyo), 102: 235-242.
13. Deutsch, J., Rapoport, S.I., and Rosenberger, T.A. 2003. Valproyl-CoA and esterified valproic acid are not found in brain of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered. Neurochem. Res. 28: 861-866.
14. Eadie, M.J., Hooper, H.D., and Dickinson, R.G. 1988. Sodium valproate-associated hepatotoxicity and its biochemical mechanisms. Med. Toxicol. 3: 85-106.
15. Edmund, G.L., and Halestrap, A.P. 1988. The kinetics of transport of lactate and pyruvate into rat hepatocytes. Biochem. J. 249: 117-126.
16. Gornall, A.G., Bardawill, C.J., and David, M.M. 1949. Determination of serum proteins by means of the biuret reaction. J. Biol. Chem. 177: 751-756.
17. Gougoux, A., and Vinay, P. 1988. Metabolic effects of valproate on dog renal cortical tubules. Can. J. Physiol. Pharmacol. 66: 88-87.
18. Griffith, A.D., Cyr, D.M., Egan, S.G., and Tremblay, G.G. 1989. Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate. Arch. Biochem. Biophys. 269: 201-207.
19. Halestrap, A.P., and Denton, R.M. 1974. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by α-cyano-4-hydroxycinnamate. Biochem. J. 138: 313-316.
20. Halestrap, A.P., and Price, N.T. 1999. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem. J. 343: 281-299.
21. Havelaar, A.C., Mancini, G.M., Beerens, C.E., Souren, R.M., and Verheijen, F.W. 1998. Purification of the lysosomal sialic acid transporter. Functional characteristics of a monocarboxylate transporter. J. Biol. Chem. 273: 34 568-34 574.
22. Ito, M., Ikeda, Y., Arnez, J.G., Finocchiaro, G., and Tanaka, K. 1990. The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl CoA dehydrogenase. Biochim. Biophys. Acta, 1034: 213-218.
23. Ji, H., and Tremblay, G.C. 1993. The relative toxicity of pivalate, benzoate, and valproate to gluconeogenesis, ureagenesis, and hippurate synthesis in isolated rat hepatocytes. Biochem. Arch. 9: 33-40.
24. Kantor, P.F., Lucien, A., Kozak, R., and Lopaschuk, G.D. 2000. 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. 86: 580-588.
25. Kesterson, J.W., Granneman, G.R., and Machinist, J.M. 1984. The hepatotoxicity of valproic acid and its metabolites in rats. 1. Toxicologic, biochemical, and histopathologic studies. Hepatology, 4: 1143-1152.
26. Kibayashi, M., Nagao, M., and Chiba, S. 1999. Influence of valproic acid on the expression of various acyl-CoA dehydrogenases in rats. Pediatr. Int. 41: 52-60.
27. Kossak, B.D., Schmidt-Sommerfeld, E., Schoeller, D.A., Rinaldo, P., Penn, D., and Tonsgard, J.H. 1993. Impaired fatty acid oxidation in children on valproic acid and the effect of L-carnitine. Neurology, 43: 2362-2368.
28. Lin, X., Adams, S.H., and Odle, J. 1996. Acetate represents a major product of heptanoate and octanoate β-oxidation in hepatocytes isolated from neonatal piglets. Biochem. J. 318: 235-240.
29. Man, K.C., and Brosnan, J.T. 1982. Inhibition of medium- and short-chain fatty acid oxidation in rat heart mitochondria by dichloroacetate. Metab. Clin. Exp. 31: 744-748.
30. McGarry, J.D., and Brown, N.F. 1997. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur. J. Biochem. 244: 1-14.
31. Na, L., Wartenberg, M., Nau, H., Hescheler, J., and Sauer, H. 2003. Anticonvulsant valproic acid inhibits cardiomyocyte differentiation of embryonic stem cells by increasing intracellular levels of reactive oxygen species. Birth Defects Res. Part A Clin. Mol. Teratol. 67: 174-180.
32. Nau, H., and Loscher, W. 1984. Valproic acid and metablites: pharmacological and toxicological studies. Epilepsia, 25(Suppl. 1): S14-S22.
33. Ponchaut, S., Van Hoof, F., and Veitch, K. 1992. In vitro effects of sodium valproate and sodium valproate metabolites on mitochondrial oxidations: relevance of CoA sequestration to the observed inhibitions. Biochem. Pharmacol. 43: 2435-2442.
34. Poole, R.C., and Halestrap, A.P. 1993. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264: C761-C782.
35. Randle, P.J. 1998. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab. Rev. 14: 263-283.
36. Rengel-Aranda, M., Gougoux, A., Vinay, P, and Lopez-Novoa, J.M. 1988. Effect of valproate on renal metabolism in the intact dog. Kidney Int. 34: 645-654.
37. Rodgers, R.L., Christe, M.E., Tremblay, G.C., Babson, J.R., and Daniels, T. 2001. Insulin-like effects of a physiologic concentration of carnitine on cardiac metabolism. Mol. Cell. Biochem. 226: 97-105.
38. Sharawi, S., Mohamoud, E.M., Nada, M., Hendrickson, S.C., and Abdel-Aleem, S. 1995. Regulation of glucose utilization by inhibition of mitochondrial fatty acid uptake in cardiac cells. Pharmacol. Res. 32: 43-47.
39. Shihabi, Z.K., Oles, K.S., McCormick, C.P., and Penry, J.K. 1992. Serum and tissue carnitine assay based on dialysis. Clin. Chem. 38: 1414-1417.
40. Suva, M.F.B., Ruiter, J.P.N., Overmars, H., Bootsma, A.H., Van Gennip, A.H., Jakobs, C., Duran, M., Tavares De Almeida, I., and Wanders, R.J.A. 2002. Complete β-oxidation of valproate: cleavage of 3-oxovalproyl-CoA by a mitochondrial 3-oxoacyl-CoA thiolase. Biochem. J. 362: 755-760.
41. Sodhi, P., Poddar, B., and Parmar, V. 2001. Fatal cardiac malformation in fetal valproate syndrome. Indian J. Pediatr. 68: 989-990.
42. Spiller, H.A., Krenzelok, E.P., Klein-Schwartz, W., Winter, M.L., Wever, J.A., Sollee, D.R., and Bangh, S.A. 2000. Multicenter case series of valproic acid ingestion: serum concentrations and toxicity. Clin. Toxicol. 38: 755-760.
43. Tein, I. 2002. Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy. J. Child Neurol. 17(Suppl. 3): S57-S82.
44. Trosper, T.L., and Philipson, K.D. 1989. Functional characteristics of the cardiac sarcolemmal monocarboxylic acid transporter. J. Membr. Biol. 112: 15-23.
45. Turnbull, D.M., Bone, A.J., Bartlett, K., Koundakjian, P.P., and Sherratt, H.A.S. 1983. The effect of sodium valproate on intermediary metabolism in isolated rat hepatocytes and intact rats. Biochem. Pharmacol. 32: 1887-1892.
46. Wu, S.P., Shyu, M.K., Liou, H.H., Gau, C.S., and Lin, C.J. 2004. Interaction between anticonvulstants and human placental carnitine transporter. Epilepsia, 45: 204-210.
47. Yao, K.W., Mao, L.F., Luo, M.J., and Schulz, H. 1994. The relationship between mitochondrial activation and toxicity of some substituted carboxylic acids. Chemico-biol. Interact. 90: 225-234.
48. Zagryadskaya, E.I., Ostretsova, I.B., and Nikiforov, A.A. 1999. Inhibitory effect of valproate on weak organic acid uptake in rat renal proximal tubules. Biochem. Pharmacol. 58: 1371-1377.