Abstract
We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7–14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.
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Abbreviations
- AEDs:
-
Antiepileptic drugs
- eCAT:
-
Erythrocyte catalase
- eSOD:
-
Erythrocyte superoxide dismutase
- FRAP:
-
Ferric reducing ability of plasma
- GPX:
-
Glutathione peroxidase
- GPX3:
-
Plasma glutathione peroxidase
- IGE:
-
Idiopathic generalised epilepsy
- pSOD:
-
Plasma superoxide dismutase
- RNS:
-
Reactive nitrogen species
- ROS:
-
Reactive oxygen species
- sCu:
-
Serum copper concentration
- SOD:
-
Superoxide dismutase
- sSe:
-
Serum selenium concentration
- sZn:
-
Serum zinc concentration
- UA:
-
Uric acid
- UAiFRAP:
-
Uric acid-independent ferric reducing ability of plasma
- VPA:
-
Valproate
References
Majkowski J (2007) Epileptogenesis—the role of oxygen stress. Epileptologia 15:225–240
Haldar S, Rowland IR, Barnett YA et al (2007) Influence of habitual diet on antioxidant status: a study in a population of vegetarians and omnivores. Eur J Clin Nutr 61:1011–1022
Nazıroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001
Ayçiçek A, Işcan A (2007) The effects of carbamazepine, valproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children. Eur Neurol 57:65–69
Torbati D, Church DF, Keller JM, Pryor WA (1992) Free radical generation in the brain precedes hyperbaric oxygen induced convulsions. Free Radic Biol Med 13:101–106
Wang JF, Azzam JE, Young LT (2003) Valproate inhibits oxidative damage to lipid and protein in primary cultured rat cerebrocortical cells. Neuroscience 116:485–489
Sudha K, Rao AV, Rao A (2001) Oxidative stress and antioxidants in epilepsy. Clin Chim Acta 303:19–24
Hamed SA, Abdellah MM, El-Melegy N (2004) Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant system in epileptic patients. J Pharmacol Sci 96:465–473
Verrotti A, Scardapane A, Franzoni E, Manco R, Chiarelli F (2008) Increased oxidative stress in epileptic children treated with valproic acid. Epilepsy Res 78:171–177
Yiş U, Seçkin E, Kurul SH, Kuralay F, Dirik E (2009) Effects of epilepsy and valproic acid on oxidant status in children with idiopathic epilepsy. Epilepsy Res 84:232–237
Commission on Classification and Terminology of the International League Against Epilepsy (1989) Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 30:389–399
Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76
Annanmaki T, Muuronen A, Murros K (2007) Low plasma uric acid level in Parkinson's disease. Mov Disord 22:1133–1137
Zagrodzki P, Nicol F, McCoy MA et al (1998) Iodine deficiency in cattle: compensatory changes in thyroidal selenoenzymes. Res Vet Sci 64:209–211
Siska IR, Avram J, Tatu C, Bunu C, Schneider F, Maties R (1999) Some aspects concerning the antioxidant capacity of venous blood in lower limbs varicose veins. Adv Exp Med Biol 471:445–452
Nebot C, Moutet M, Huet P, Xu JZ, Yadan JC, Chaudiere J (1993) Spectrophotometric assay of superoxide dismutase activity based on the activated autoxidation of a tetracyclic catechol. Anal Biochem 214:442–451
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Chapman SA, Wacksman GP, Patterson BD (2001) Pancreatitis associated with valproic acid: a review of the literature. Pharmacotherapy 21:1549–1560
Pippenger CE, Meng X, Van Lente F, Rotliner AD (1989) Valproate therapy depresses GSHpX and SOD enzyme activity. A possible mechanism for valproate induced idiosyncratic drug toxicity. Clin Chem 35:1173
Maertens P, Dyken P, Graf W et al (1995) Free radicals, anticonvulsants, and the neuronal ceroid-lipofuscinoses. Am J Med Genet 57:225–228
Armutcu F, Ozerol E, Gurel A et al (2004) Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children. Biol Trace Elem Res 102:1–10
Yüksel A, Cengiz M, Seven M, Ulutin T (2000) Erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children with valproate and carbamazepine monotherapy. J Basic Clin Physiol Pharmacol 11:73–81
Turkdogan D, Toplan S, Karakoc Y (2002) Lipid peroxidation and antioxidative enzyme activities in childhood epilepsy. J Child Neurol 17:673–676
Cengiz M, Yüksel A, Seven M (2000) The effects of carbamazepine and valproic acid on the erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children. Pharmacol Res 41:423–425
Verrotti A, Basciani F, Trotta D et al (2002) Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 48:71–75
Solowiej E, Sobaniec W (2003) The effect of antiepilepticdrug therapy on antioxidant enzyme activity and serum lipid peroxidation in young patients with epilepsy. Neurol Neurochir Pol 37:991–1003
Mariani E, Cornacchiola V, Polidori MC et al (2006) Antioxidant enzyme activities in healthy old subjects: influence of age, gender and zinc status: results from the Zincage Project. Biogerontology 7:391–398
Marklund S (1980) Distribution of CuZn superoxide dismutase and Mn superoxide dismutase in human tissues and extracellular fluids. Acta Physiol Scand Suppl 492:19–23
Johnson WT, Johnson LA, Lukaski HC (2005) Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats. J Nutr Biochem 16:682–692
Harvey LJ, McArdle HJ (2008) Biomarkers of copper status: a brief update. Brit J Nutr 99:S10–S13
Perucca E (2002) Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 16:695–714
Morland C, Boldingh KA, Iversen EG, Hassel B (2004) Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake. J Cereb Blood Flow Metab 24:1226–1234
Ueda Y, Yokoyama H, Nakajima A et al (2002) Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus. Exp Brain Res 147:219–226
Mariani E, Mangialasche F, Feliziani FT et al (2008) Effects of zinc supplementation on antioxidantenzyme activities in healthy old subjects. Exp Gerontol 43:445–451
Hughes S, Samman S (2006) The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis. J Am Coll Nutr 25:285–291
Kürekçi AE, Alpay F, Tanindi S et al (1995) Plasma trace element, plasma glutathione peroxidase, and superoxide dismutase levels in epileptic children receiving antiepileptic drug therapy. Epilepsia 36:600–604
Barbeau A, Donaldson J (1974) Zinc, taurine, and epilepsy. Arch Neurol 30:52–58
Higashi A, Ikeda T, Matsukura M, Matsuda I (1982) Serum zinc and vitamin E concentrations in handicapped children treated with anticonvulsants. Dev Pharmacol Ther 5:109–113
Schott GD, Delves HT (1978) Plasma zinc levels with anticonvulsant therapy. Br J Clin Pharmacol 5:279–280
Acknowledgements
This study was partly supported by grant from Rinnekoti Research Foundation. The first author thanks Prof. Gerhard Bauer, Prof. Joanna Jędrzejczak and Prof. Jerzy Majkowski for their valuable comments.
Conflict of Interest
Dr. E. Płonka-Półtorak has received support for attendance in congresses in epilepsy and neurology and speaker’s honoraria from UCB-Pharma and Sanofi-Aventis. None of these relations is related to current submission. The remaining authors confirm that there are no conflicts of interest.
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Płonka-Półtorak, E., Zagrodzki, P., Chłopicka, J. et al. Valproic Acid Modulates Superoxide Dismutase, Uric Acid-Independent FRAP and Zinc in Blood of Adult Epileptic Patients. Biol Trace Elem Res 143, 1424–1434 (2011). https://doi.org/10.1007/s12011-011-9003-3
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DOI: https://doi.org/10.1007/s12011-011-9003-3