Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-28T19:23:03.209Z Has data issue: false hasContentIssue false
  • English
  • Français

Assessment of low-density lipoprotein oxidation, paraoxonase activity, and arterial distensibility in epileptic children who were treated with anti-epileptic drugs

Published online by Cambridge University Press:  02 June 2010

Mustafa Yildiz ,
Gonul Simsek ,
Hafize Uzun ,
Serap Uysal ,
Sevim Sahin  and
Huriye Balci
Mustafa Yildiz*
Affiliation:
Department of Physiology, Istanbul University, Istanbul, Turkey Department of Cardiology, Kartal Kosuyolu Yuksek Ihtisas Educational and Research Hospital, Istanbul University, Istanbul, Turkey
Gonul Simsek
Affiliation:
Department of Physiology, Istanbul University, Istanbul, Turkey
Hafize Uzun
Affiliation:
Department of Biochemistry, Istanbul University, Istanbul, Turkey
Serap Uysal
Affiliation:
Department of Pediatric Neurology, Istanbul University Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
Sevim Sahin
Affiliation:
Department of Pediatric Neurology, Istanbul University Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
Huriye Balci
Affiliation:
Cerrahpaşa Medical Faculty, Fikret Biyal Research Laboratory, Istanbul University, Istanbul, Turkey
*
Correspondence to: M. Yildiz, Associate Professor, MD, PhD, Cardiologist, Internal Medicine Specialist and Physiologist, Department of Cardiology, Kartal Kosuyolu Yuksek Ihtisas Educational and Research Hospital, Istanbul, Turkey. Tel: +90 532 371 17 01; Fax: +90 216 459 63 21; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Studies show that anti-epileptic drugs increase oxidative stress. Thus, low-density lipoprotein oxidation increases and atherogenesis is induced. Paraoxonase-associated high-density lipoprotein protects low-density lipoprotein and high-density lipoprotein oxidation. The effects of anti-epileptic drugs on paraoxonase activity has not been investigated yet. The aim of this study is to investigate the effect of anti-epileptic drugs on paraoxonase activity, lipid profiles, folat, vitamin B12, homocysteine, thyroid hormones, apolipoprotein A-1, total anti-oxidant capacity, malondialdehyd, nitric oxide, and oxidised low-density lipoprotein. The association with carotid–femoral pulse wave velocity and current biochemical parameters had been searched for assessing the effects of anti-epileptic drugs on the vascular system.

Patients and methods

We recruited 59 epileptic patients treated with anti-epileptic drugs and 23 controls (group IV) at least 6 months ago. The epileptic group was divided into three groups by receiving anti-epileptic drugs as follows: group I: carbamazepine, group II: valproic acid, and group III: carbamazepine and valproic acid. Arterial distensibility was assessed with the Complior device.

Results

There was no difference between the current biochemical parameters in epileptic children. Serum-free T4 was decreased, when compared with group IV. Thyroid-stimulating hormone was increased in group II, compared with group IV. The carotid–femoral pulse wave velocity was increased in group III, compared with group IV. The carotid–femoral pulse wave velocity was correlated with thyroid-stimulating hormone and valproic acid levels.

Conclusions

Anti-epileptic drugs may induce atherogenesis by affecting the thyroid hormones. According to the current data, the effects of thyroid hormones on vascular system may be independent of other biochemical markers. Epileptic patients using anti-epileptic drugs must be followed closely for arterial stiffness, and also for the development and progression of atherosclerosis.

Keywords

Carbamazepinevalproic acidarterial distensibilityparaoxanaseoxidised low-density lipoprotein
Type
Original Articles
Information
Cardiology in the Young , Volume 20 , Issue 5 , October 2010 , pp. 547 - 554
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Verrotti, A, Domizio, S, Angelozzi, B, Sabatino, G, Morgese, G, Chiarelli, F. Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants. J Paediatr Child Health 1997; 33: 242–245.CrossRefGoogle ScholarPubMed
2. Karabiber, H, Sonmezgoz, E, Ozerol, E, Yakinci, C, Otlu, B, Yologlu, S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev 1997; 25: 113–115.CrossRefGoogle Scholar
3. Li, D, Mehta, JL. Oxidized LDL, a critical factor in atherogenesis. Cardiovasc Res 2005; 68: 353–354.CrossRefGoogle ScholarPubMed
4. Rodríguez Esparragón, F, Hernández Trujillo, Y, Macías Reyes, A, Hernández Ortega, E, Medina, A, Rodríguez Pérez, JC. Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis. Rev Esp Cardiol 2006; 59: 154–164.CrossRefGoogle ScholarPubMed
5. Asmar, R, Benetos, A, Topouchian, J, et al. Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension 1995; 26: 485–490.CrossRefGoogle ScholarPubMed
6. Saha, N, Roy, AC, Teo, SH, Tay, JS, Ratnam, SS. Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins. Clin Genet 1991; 40: 277–282.CrossRefGoogle ScholarPubMed
7. Buege, JA, Aust, SD. Microsomal lipid peroxidation. Methods Enzymol 1978; 12: 302–310.CrossRefGoogle Scholar
8. Mackness, B, Durrington, PN, Mackness, MI. Human serum paraoxonase. Gen Pharm 1998; 3: 329–336.CrossRefGoogle Scholar
9. Ikeda, Y, Suehiro, T, Itahara, T, et al. Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients. Clin Nephrol 2007; 67: 358–365.CrossRefGoogle ScholarPubMed
10. Cabana, VG, Reardon, CA, Feng, N, Neath, S, Lukens, J, Getz, GS. Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response. J Lipid Res 2003; 44: 780–792.CrossRefGoogle ScholarPubMed
11. Reddy, MN. Effect of anticonvulsant drugs on plasma total cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A and B in children with epilepsy. Proc Soc Exp Biol Med 1985; 180: 359–363.CrossRefGoogle Scholar
12. Dagre, AG, Lekakis, JP, Papaioannou, TG, et al. Arterial stiffness is increased in subjects with hypothyroidism. Int J Cardiol 2005; 103: 1–6.CrossRefGoogle ScholarPubMed
13. Isojärvi, JIT, Turkka, J, Pakarinen, AJ, Kotila, M, Rättyä, J, Myllylä, VV. Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 2001; 42: 930–934.CrossRefGoogle ScholarPubMed
14. Villa, SM, Alexander, NM. Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone synthesis in rat thyroid glands. Endocr Res 1987; 13: 385–397.CrossRefGoogle ScholarPubMed
15. Aanderud, S, Strandjord, RE. Hypothyroidism induced by anti-epileptic therapy. Acta Neurol Scand 1980; 61: 330–332.CrossRefGoogle ScholarPubMed
16. Hegedüs, L, Hansen, M, Lühdorf, K, Perrild, H, Feldt-Rasmussen, U, Kampmann, JP. Increased frequency of goitre in epileptic patients on long-term phenytoin or carbamazepine treatment. Clin Endocrinol 1985; 23: 423–429.CrossRefGoogle ScholarPubMed
17. Wilkinson, IB, Cockcroft, JR. Mind the gap: pulse pressure, cardiovascular risk, and isolated systolic hypertension. Am J Hypertens 2000; 13: 1315–1317.CrossRefGoogle Scholar
18. Ojamaa, K, Balkman, C, Klein, I. Acute effects of thyroid hormone on vascular smooth muscle. Thyroid 1996; 6: 505–512.CrossRefGoogle ScholarPubMed
19. Mizuma, H, Murakami, M, Mori, M. Thyroid hormone activation in human vascular smooth muscle cells; expression of type II deiodinase activity. Circ Res 2001; 88: 313–318.CrossRefGoogle Scholar
20. Bengel, FM, Nekolla, SG, Ibrahim, T, Weniger, C, Ziegler, SI, Schwaiger, M. Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. J Clin Endocrinol Metab 2000; 85: 1822–1827.CrossRefGoogle ScholarPubMed
21. Davignon, J, Ganz, P. Role of endothelial dysfunction in atherosclerosis. Circulation 2004; 109 (Suppl 1): III27–III32.CrossRefGoogle ScholarPubMed
22. Akinci, B, Comlekci, A, Yener, S, et al. The alteration of serum soluble CD40 ligand levels in overt and subclinical hypothyroidism. Hormones (Athens) 2007; 6: 327–333.CrossRefGoogle ScholarPubMed
23. Orzechowska-Pawilojc, A, Sworczak, K, Lewczuk, A, Babinska, A. Homocysteine, folate and cobalamin levels in hypothyroid women before and after treatment. Endocr J 2007; 54: 471–476.CrossRefGoogle ScholarPubMed
24. Ozmen, B, Ozmen, D, Parildar, Z, Mutaf, I, Turgan, N, Bayindir, O. Impact of renal function or folate status on altered plasma homocysteine levels in hypothyroidism. Endocr J 2006; 53: 119–124.CrossRefGoogle ScholarPubMed
25. Hanna, AN, Feller, DR, Witiak, DT, Newman, HA. Inhibition of low density lipoprotein oxidation by thyronines and probuclo. Biochem Pharmacol 1993; 45: 753–762.CrossRefGoogle Scholar
26. Squizzato, A, Gerdes, VE, Brandjes, DP, Büller, HR, Stam, J. Thyroid diseases and cerebrovascular disease. Stroke 2005; 36: 2302–2310.CrossRefGoogle ScholarPubMed
27. Crisp, MS, Lane, C, Halliwell, M, Wynford-Thomas, D, Ludgate, M. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997; 82: 2003–2005.CrossRefGoogle ScholarPubMed
28. Powell, J, Zadeh, JA, Carter, G, Greenhalgh, RM, Fowler, PB. Raised serum thyrotrophin in women with peripheral arterial disease. Br J Surg 1987; 74: 1139–1141.CrossRefGoogle ScholarPubMed
29. Nanda, N, Bobby, Z, Hamide, A. Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism. Clin Chem Lab Med 2008; 46: 674–679.CrossRefGoogle ScholarPubMed
30. Duntas, LH, Mantzou, E, Koutras, DA. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid 2002; 12: 1003–1007.CrossRefGoogle ScholarPubMed
31. Duman, D, Demirtunc, R, Sahin, S, Esertas, K. The effects of simvastatin and levothyroxine on intima-media thickness of the carotid artery in female normolipemic patients with subclinical hypothyroidism: a prospective, randomized-controlled study. J Cardiovasc Med (Hagerstown) 2007; 8: 1007–1011.CrossRefGoogle ScholarPubMed
32. Coria, MJ, Pastrán, AI, Gimenez, MS. Serum oxidative stress parameters of women with hypothyroidism. Acta Biomed 2009; 80: 135–139.Google ScholarPubMed
33. Azizi, F, Raiszadeh, F, Solati, M. Serum paraoxonase 1 activity is decreased in thyroid dysfunction. J Endocrinol Invest 2003; 26: 703–709.CrossRefGoogle ScholarPubMed
34. Baskol, G, Atmaca, H, Tanriverdi, F, Baskol, M, Kocer, D, Bayram, F. Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes 2007; 115: 522–526.CrossRefGoogle ScholarPubMed
35. Yavuz, DG, Yüksel, M, Deyneli, O, Ozen, Y, Aydin, H, Akalin, S. Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients. Clin Endocrinol (Oxf) 2004; 61: 515–521.CrossRefGoogle ScholarPubMed
36. Młodzikowska-Albrecht, J, Steinborn, B, Zarowski, M. Cytokines, epilepsy and epileptic drugs – is there a mutual influence? Pharmacol Rep 2007; 59: 129–138.Google Scholar
37. Shiah, IS, Yatham, LN, Yeh, CB, Ravindran, AV. Effect of valproate on plasma levels of interleukin-6 in healthy male humans. Int Clin Psychopharmacol 2005; 20: 295–298.CrossRefGoogle ScholarPubMed
38. Verrotti, A, Basciani, F, Trotta, D, Greco, R, Morgese, G, Chiarelli, F. Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte chemoattractant protein-1. Clin Exp Med 2001; 1: 133–136.CrossRefGoogle ScholarPubMed