Effects of Valproic Acid Administration on Cardiovascular Risk Factors in Male Albino Rats
Asian Journal of Research in Cardiovascular Diseases,
Background: Valproic acid (VPA) is an antiepileptic drug with a well-documented hepatotoxic effect among other several side effects. However, the effect of valproic acid administration on lipid profile and cardiovascular risk factors remains inconclusive and highly controversial.
Method: In order to investigate the effects of valproic acid on lipid profile, male albino rats were treated with valproic acid at a dose of 7.14 mg/kg body weight intraperitoneally for two and four weeks while a group was allowed to recover for seven days after four weeks of valproic acid administration.
Results: Administration of valproic acid induced dyslipidemia in different compartments of the animals under investigation. Hypocholesterolemia characterized the effect of valproic acid administration in the LDL+VLDL while hypertriglyceridemia was the hallmark of its effect in all blood compartments although hypertriglyceridemia effect drops significantly when rats were allowed to recover for 7 days. In the tissues, valproic acid administration did not significantly affect cholesterol and triglyceride levels but phospholipid levels in the heart and kidney were significantly decreased by 46.03% and 38.57% after 2 weeks of administration while phospholipid levels in other tissues compartment were not affected.
Conclusion: The results presented in this study are in support of the argument that valproic acid administration does not significantly affect lipid profile because the perturbations of lipid content observed are non-lipotoxic and may not pose a cardiovascular disease risk.
- Valproic acid
How to Cite
Fan HC, Lee HS, Chang KP, Lee YY, Lai HC, Hung PL. The impact of anti-epileptic drugs on growth and bone metabolism. Internat Journal of Molecular Sciences. 2016;17:1–22.
Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of time-honoured drug. Lancet Neurol. 2016;15: 210–218.
Silva MF, Aires CC, Luis PB, Ruiter JP, Jist LI, Duran M. Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review. J. Inherit. Metab. Dis. 2008;31:205–216.
Olsen K, Taubøll E, Gjerstad L. Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults. Acta Neurol. Scand., Suppl. 2007; 187:51–54.
Ghodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, Altman RB, Klein TE. Valproic acid pathway: Pharmacokinetics and pharmacodynamics. Pharmacogenetics Genomics. 2013;23(4): 236-241
Nanau RM, Neuman MG. Adverse drug reactions induced by valproic acid. Clin. Biochem. 2013;46:1323–1338.
Belcastro V, D’Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Research. 2013;107:1–8.
Luo X, Zhang M, Deng L, Zhao J. Effects of valproate on the carotid artery intima-media thickness in epileptics. Indian Journal of Pharmacology. 2015;47:45– 48.
Płonka-Półtorak E, Zagrodzki P, Kryczyk-Kozioł J, Westermarck T, Kaipainen P, Kaski M, Atroshi F. Does valproate therapy in epileptic patients contribute to changing atherosclerosis risk factors? The role of lipids and free fatty acids. Pharmacological Reports. 2016;68:1339–1344.
Auley MTM, Mooney KM. Computationally Modelling Lipid Metabolism and Aging: A Mini-review. Computational and Structural Biotechnology Journal. 2015;13:38–46.
Yang L, Li M, Shan Y, Shen S, Bai Y, Liu H. Recent advances in lipidomics for disease research. J. Sep. Sci. 2016;39:38–50.
Sakakura K, Nakano M, Otsuka F, Ladich E, Kolodgie FD, Virmani R. Pathophysiology of atherosclerosis plaque progression. Heart, Lung, and Circulation. 2013;22:399–411.
Owoade AO, Airaodion AI, Adetutu A, Akinyomi OD. Levofloxacin -induced dyslipidemia in male albino rats Asian Journal of Pharmacy and Pharmacology. 2018;4(5):620-629.
Gidez LI, Miller GJ, Burstein M, Slagle S, Eder HA. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. Journal of Lipid Research. 1982;23:1206–1223.
Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biology Chemistry. 1957;226:497–509.
Stewart JC. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Analitical Biochemistry. 1980;104:10–14.
Rose HG, Oklander M. Improved procedure for the extraction of lipids from human erythrocytes. Journal of Lipid Research. 1965;6:428–431.
Eder K, Kirchgessner M. The effect of zinc deficiency on erythrocyte membrane lipids of force-fed rats receiving a diet containing coconut oil or fish oil. Journal of Trace Element and Electrolytes in Health and Disease. 1994;8:63–73.
Kriketos AD, Furler SM, Gan SK, Poynten AM, Chisholm DJ, Campbell LV. Multiple indexes of lipid availability are independently related to whole body insulin action in healthy humans. Journal of Clinical Endocrinology and Metabolism. 2003;88: 793–798.
Chrysohoou C, Panagiotakos DB, Pitsavos C, Kosma K, Barbetseas J, Karagiorga M, Ladi I, Stefanadis C. Distribution of serum lipids and lipoproteins in patients with beta thalassaemia major; an epidemiological study in young adults from Greece. Lipids Health Dis. 2004;3:3.
Ginsberg HN. Lipoprorein metabolism and its relationship to atherosclerosis. Med Clin North Am. 1994;78:1-20.
Glew RH, Williams M, Conn CA, Cadena SM, Crossey M, Okolo SN. Cardiovascular disease risk factors and diet of fulani pastorialists of northern Nigeria. Am J Clin Nutr. 2001;74:730-736.
van der Sande MA, Inskip HM, Jaiteh KO, Maine NP, Walraven GE, Hall AJ, McAdam KP. Changing causes of death in the West African town of Banjul, 1942–1997. Bull World Health Organ. 2001;79:133- 141.
Lecerf, JM. Phytosterols and cardiovascular risk. Nutr Clin Metab. 2007;21:17–27
Rajeshwari T, Raja B, Manivannan J, Silambarasan T, Dhanalakshmi T. Valproic acid prevents the deregulation of lipidmetabolism and renal renin–angiotensin system in l-NAME induced nitric oxide deficient hypertensive rats. Environmental Toxicology and Pharmacology. 2014;37: 936-945
Abbas AM, Kadhem ZA, Hussein MH. Effects of administration of two different doses from valproic acid on lipid profile in male rats. International Journal of Research in Applied, Natural and Social Sciences. 2015;3(12):55-58.
Jaeri S. The long term effect of valproic acid in lipid profile among adult. Journal of the Neurological Sciences. 2019;405S: 105447.
Eltom TM, Mohamed NE, Bashir AM, Eltom AE. Effects of antiepileptic drugs on serum lipids profile among young adult Sudanese patient with epilepsy at Aljazeera State. GSC Biological and Pharmaceutical Sciences. 2021;14(01):175–182.
Law MR. Lowering heart disease risk with cholesterol reduction: Evidence from observational studies and clinical trials. Eur Heart J Suppl. 1999;1:S3-S8.
Raffai RL, Weisgraber KH. Cholesterol: from heart attacks to Alzheimer's disease J Lipid Res. 2003;44(8):1423-30
Gesquiere L, Loreau N, Minnich A, Davignon J, Blache D. Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells. Free Radical Biology and Medicine. 1999;27(1–2):134–45.
Sawada H, Takami K, Asahi SA. toxicogenomic approach to drug-induced phospholipidosis: Analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicological Sciences. 2005;83:282–292.
Kojima M, Masui T, Nemoto K, Degawa M. Lead nitrate induced development of hypercholesterolemia in rats: sterol independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis. Toxicology Letters. 2004;154: 35–44.
Nelson DL, Cox MM. Lehniger principles of biochemistry (4th edition) W.H. Freeman and Co., New York. ISBN 1-4039-4876-3. Newer agents. Clinical Infectious Diseases. 2005;28(2):352-364.
Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell Metabolism. 2012;15:805–812.
Pulinilkunnil T, Rodrigues B. Cardiac lipoprotein lipase: metabolic basis for diabetic heart disease. Cardiovascular Research. 2006;69:329–340.
Lee J, Goldberg IJ. Lipoprotein lipase-derived fatty acids: physiology and dysfunction. Current Hypertension Report. 2007;9:462–466.
Saxena U, Witte LD, Goldberg IJ. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids. Journal of Biological Chemistry. 1989;264: 4349–4355.
Criqui MH, Heiss G, Cohn R, Cowan LD, Suchindran CM, Bangdiwala S, Kritchevsky S, Jacobs DR Jr, O'Grady HK, Davis CE. Plasma triglyceride level and mortality from coronary heart disease. New England Journal of Medicine. 1993;328:1220- 1225.
Assmann G, Cullen P, Schulte H. The Munster Heart Study (PROCAM). Results of follow-up at 8 years. European Heart Journal. 1998;19(suppl A):A2-11.
Hodis HN, Mack WJ, Krauss RM, Alaupovic P. Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: clinical aspects. Clinical Cardiology. 1999;22:(II)15-20.
Zilversmit DB. Atherogenesis: A postprandial phenomenon. Circulation. 1979;60:473- 485.
Bangur CS, Howland JL, Katyare SS. Thyroid hormone treatment alters phospholipid composition and membrane fluidity of rat brain mitochondria. Biochemical Journal. 1995;305:29- 32.
Gatica LV, Vega VA, Zirulnik F, Oliveros LB, Gimenez MS. Effects of Vitamin A Deficiency on the Lipid Metabolism in Rat Aorta. Journal of Vascular Research. 2006; 43:602-610.
Abe A, Hiraoka M, Shayman JAA. Role for lysosomal phospholipase A2 in drug-induced phospholipidosis. Drug Metabolism Letters. 2007;1:49–53.
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