Research Journal of Pharmacology and Pharmacodynamics

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Elevated Singlet Oxygen Dependent Tissue Injury as well as Diminished Activity of Antioxidative Defense Mechanism by Sodium Valproate Clinical Course in Epileptic Children


Affiliations
1 PG Department of Biochemistry, SRM College of Arts and Science, Chennai-603 203, India
2 Faculty of Medicine and Health Science, Universititi Sultan Zainal Abidin, 20400 Kuala Terengganu, Terengganu, Malaysia
     

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The study was aimed to determine the biochemical changes in the free radical profile and antioxidant enzyme status in epileptic children before and after treatment with VPA monotherapy. Methods: We have studied the levels of serum LPO (MDA), erythrocyte antioxidants (GSH, GPx, SOD and CAT) in 25 epileptic children before and after treatment with sodium valproate and compared them against 25 healthy children. Results: The results showed that MDA levels were increased (p<0.001) in epileptic children under VPA treatment compared to the controls. Antioxidant enzymes GPx, SOD, CAT activities were decreased (p<0.001) in epileptic children receiving VPA monotherapy whereas no significant changes when compared between before and after treatment with VPA. The level of GSH was also decreased (p<0.001) in follow-up cases of epileptic children receiving VPA therapy. Conclusion: It was hypothesized that the oxidants-antioxidants balance were modified further by sodium valproate in epileptic children.

Keywords

Sodium Valproate, Antioxidants, Lipid Peroxidation, Oxidative Stress, Epilepsy, Free Radical.
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  • Choi BH. Oxygen, antioxidants and brain dysfunction. Yonsei Med J 1993; 34:1-10.

  • Delanty N, Dichter MA. Oxidative injury in the nervous system. Acta Neurol Scand 1998; 98:145-153.

  • Pincemial J. Free radicals and antioxidants in human diseases. In analysis of free radicals in biological systems. Fravier AE, Cadet J, Kalyanaraman B, Fontecave M and Pierre JL eds. Birkhauser Verlag, Basel 1995; pp 83-98.

  • Maertens P, Dyken P, Graf W, Pippenger C, Chronister R, Shah A. Free radicals, anticonvulsants and neuronal ceroid lipofuscinosis. Am J Med Genet 1995; 57:225-228.

  • Yuksel A,Cengiz M, Seven M,Ulutin T. Erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children with valproate and carbamazepine monotherapy. J Basic Clin Pharmacol 2000; 11: 73-81.

  • Cengiz M, Yuksel A, Seven M. The effects of carbamazepine and valproic acid on the erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children. Pharmacol Res 2000; 41: 423-425.

  • Jesberger JA, Richardson JS. Oxygen free radicals and brain dysfunction. Int J Neurosci 1991; 57: 1-7.

  • Verrotti A, Basciani F, Trotta D, Pomilio MP, Morgese G, Chiarelli F. 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 2002; 48: 71-75.

  • Hunter FE, Geblechi JM, Hofgten PE, Einstein S, Scott A. Determination of plasma malondialdehyde like materials. J Biol Chem 1963; 238: 614.

  • Moron MS, Depierre JW, Mannervk B. Levels of glutathione, glutathione reductase and glutathione-s-transferase activities in rat lung and liver. Biochem Biophys Acta 1979; 582: 67-68.

  • Rotruck JT, Pope AL, Ganther HE, Swanson AB. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973; 197: 588-590.

  • Misra H and Fridovich I. The role of superoxide dismutase anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170.

  • Aebi H. Catalase. In: Bergmeyer HV, editor. Methods in enzymatic analysis. Vol.2. New York: Academic Press, 1974: p.674-684.

  • Drabkin DL, Austin JH. Spectrometric studies for hemoglobin derivatives in human, dog and rabbit blood. J Biol Chem 1932; 98: 719-783.

  • Oliver CN, Starke-Reed PE, Stadtman ER, Lin GJ, Correy JM, Floyd RA. Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion induced injury to gerbil brain. Proc Natl Acad Sci USA 1990; 87: 5144-7.

  • Frantseva MV, Perez Valazquez JL, Tsorakkidis G, Mendonca AJ, Mills LR, Carlen PL, Burnham MW. Oxidative stress isinvolved in seizre-induced neurodegeneration in the kindling model of epilepsy. Neurosci 2000; 97: 431-435.

  • Graf WD, Oleinik OE, Glauser TA, Maertens P, Eder DN, Pippenger CE. Alrered antioxidant activities in children with a serious side adverse experience related to valproic acid therapy. Neuropediatrics 1998; 29: 195-201.

  • Liu C, Wu H, Kao S, Wei Y.Serum trace elements, glutathione, copper/zinc superoxide dismutase, and lipid peroxidation in epileptic patients with phenytoin or carbamazepine monotherapy. Clin Neuropharmacol 1998; 21: 62-64.

  • Niketic V, Ristic S, Saicic ZS, Spasic M, Buzadzic B, Stojkevic M. Activities of antioxidant enzymes and formation of the glutathione adduct of hemoglobin (Hb ASSG) in epileptic patients with long-term antiepileptic therapy. Farmaco 1995; 50: 811-813.

  • Weber GR, Maertens P, Meng XZ, Pippenger CE. Glutathione peroxidase deficiency and childhood seizures. Lancet 1991; 337: 1443-4.

  • Rettie AE, Rettenmeier AW, Howald WN and Baillie TA. Cytochrome P450-catalyzed formation of 4-en VPA, a toxic metabolite of valproic acid. Science 1987; 235: 890-893.

  • Rettenmeier AW, Prickett KS, Gordon PW, Bjorge SM, Change SL, Levy RH,et al. Studies on the biotransformation in the prefused rat liver of 2-n-propyl-4 pentenoic acid, a metabolite of the antiepileptic drug valproic acid. Evidence for the formation of chemically reactive intermediates. Drug Metab Dispos 1985; 13: 81-96.

  • Kassahun K, Hu P, Grillo MP, Davis MR, Jin L, Baillie TA. Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A dependent and independent processes. Chem Biol Interact 1994; 90: 253-275.

  • Tang W and Abbott FS. Bioactivation of a toxic metabolite of vlproic acid, (E)-2-propyl-2,4-pentadienoic acid, via glucuronidation. LC/MS/MS characterization of the GSH-glucuronide disconjugates. Chem Res Toxicol 1996a; 9: 517-526.

  • Kassahun K, Farrell K, Abbott F.Identification and characterization of the glutathione and N-acetylcysteine conjugated of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. Drug Metab Dispos 1991; 19: 525-535.

  • Pigeolet E, Remacle J. Susceptibility of glutathione peroxidase to proteolysis after oxidative alteration by peroxides and hydroxyl radicals. Free Rad Biol Med 1991; 11: 191-5.

  • Mirault ME, Tremblay A, Furling D, Trepanier G, Dugre F, Puymirat J, Pothier F. Transgenic glutathione peroxidase mice models for neuroprotection studies. Ann N Y Acad Sci 1994; 738: 104-15.

  • Pippenger CE, Meng X, Von Lente F, Rothner AD. Valproate therapy suppresses GSH-Px and SOD enzyme activity. A possible mechanism for VA induced idiosyncratic drug toxicity. Clin Chem 1989; 35: 1173

  • Hamed SA, Abdellah MM, E1-Melegy N. Blood levels of trace elements, electrolytes and oxidative stress/antioxidant systems in epileptic patients. J Pharmacol Sci 2004; 96: 465-473.

  • Kurekci AE, Alpay F, Tanindi S, Gokcay E, Ozcan O, Akin R et al., Plasma trace element, plasma glutathione peroxidase and superoxide dismutase levels in epileptic children receiving AEDs therapy. Epilepsia 1995; 36: 600-604.

  • Barbara Artemowicz, Ellibieta Solowiej, Wojciech Sobaniec. The disturbance of the oxidants-antioxidants Balance in epileptic children. IJNN 2004; 1: 27-31.

  • Liao KH, Mei OY, Zhou JC. Determination of antioxidants in plasma and erythrocyte in patients with epilepsy. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2004; 29(1): 72-4.


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  • Elevated Singlet Oxygen Dependent Tissue Injury as well as Diminished Activity of Antioxidative Defense Mechanism by Sodium Valproate Clinical Course in Epileptic Children

Abstract Views: 220  |  PDF Views: 2

Authors

N. Sangeetha
PG Department of Biochemistry, SRM College of Arts and Science, Chennai-603 203, India
U. S. Mahadeva Rao
Faculty of Medicine and Health Science, Universititi Sultan Zainal Abidin, 20400 Kuala Terengganu, Terengganu, Malaysia

Abstract


The study was aimed to determine the biochemical changes in the free radical profile and antioxidant enzyme status in epileptic children before and after treatment with VPA monotherapy. Methods: We have studied the levels of serum LPO (MDA), erythrocyte antioxidants (GSH, GPx, SOD and CAT) in 25 epileptic children before and after treatment with sodium valproate and compared them against 25 healthy children. Results: The results showed that MDA levels were increased (p<0.001) in epileptic children under VPA treatment compared to the controls. Antioxidant enzymes GPx, SOD, CAT activities were decreased (p<0.001) in epileptic children receiving VPA monotherapy whereas no significant changes when compared between before and after treatment with VPA. The level of GSH was also decreased (p<0.001) in follow-up cases of epileptic children receiving VPA therapy. Conclusion: It was hypothesized that the oxidants-antioxidants balance were modified further by sodium valproate in epileptic children.

Keywords


Sodium Valproate, Antioxidants, Lipid Peroxidation, Oxidative Stress, Epilepsy, Free Radical.

References