Relationship Between Serum Malondialdehyde (MDA) Levels With Seizure Frequency In Epilepsy Patients With Combination Of Phenytoin And Valproic Acid

Authors

  • Aji Noegroho Neurology Division, Medical Faculty of Diponegoro University/Central General Hospital of Kariadi Semarang, Indonesia, Indonesia
  • Aris Catur Bintoro Neurology Division, Medical Faculty of Diponegoro University/Central General Hospital of Kariadi Semarang, Indonesia, Indonesia
  • Dwi Pudjonarko Neurology Division, Medical Faculty of Diponegoro University/Central General Hospital of Kariadi Semarang, Indonesia, Indonesia

DOI:

https://doi.org/10.36408/mhjcm.v11i1.987

Keywords:

MDA, frequency of seizures, length of treatment, age of onset of epilepsy

Abstract

Background: Oxidative stress is believed to be one of the factors involved in the pathogenesis of epileptogenic where lipid peroxidation occurs which produces Malondialdehyde (MDA). Epilepsy and some Antiepileptic Drugs (AEDs) can improve or worsen seizure frequency thereby significantly changing blood MDA levels.

 

Objective: To determine the relationship between serum MDA levels and seizure frequency in epileptic patients treated with AEDs, a combination of phenytoin and valproic acid.

 

Methods: A cross-sectional study with consecutive sampling of 46 subjects (with epilepsy receiving combination therapy with phenytoin and valproic acid. The research was conducted at the Neurology Policlinic at RSUP Dr. Kariadi in December 2022 – February 2023. MDA levels were measured using the Enzyme Linked Immunosorbent Assay (ELISA) method. The relationship between serum MDA levels and seizure frequency was analyzed using Spearman's test since both of the variables are ordinal scale, the results were significant if p<0.05.

 

Results: There was no relationship between MDA levels and seizure frequency in epileptic patients with the combination of phenytoin and valproic acid. (p=0.516) There is a significant relationship between the frequency of seizures and the length of treatment (p=0.026) with a weak negative correlation (rho=0.328). There is a significant relationship between the frequency of seizures and the age of onset of epilepsy (p=0.037) with a weak negative correlation (rho=0.309).

Conclusion: There is a significant relationship between the frequency of seizures with the length of treatment and the age of onset of epilepsy.

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References

1. Ersan S, Cigdem B, Bakir D, Dogan HO. Determination of levels of oxidative stress and nitrosative stress in patients with epilepsy. Epilepsy Res [Internet]. 2020;164(October 2019):106352. Available from: https://doi.org/10.1016/j.eplepsyres.2020.106352

2. Aguiar CCT, Almeida AB, Arajo PVP, Abreu RNDC De, Chaves EMC, Vale OC Do, et al. Oxidative stress and epilepsy: Literature review. Oxid Med Cell Longev. 2012;2012.

3. Dönmezdil N, Çevik MU, Özdemir HH, Taşin M. Investigation of PONI activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment. Neuropsychiatry DisTreat. 2016;12:1013–7.

4. Nisha Y, Bobby Z, Wadwekar V. Biochemical derangements related to metabolic syndrome in epileptic patients on treatment with valproic acid. Seizure [Internet]. 2018;60:57–60. Available from: https://doi.org/10.1016/j.seizure.2018.06.003

5. Pandey MK, Mittra P, Maheshwari PK. The lipid peroxidation product as a marker of oxidative stress in epilepsy. J Clin Diagnostic Res. 2012;6(4 SUPPL. 2):590–2.

6. Menon B, Ramalingam K, Kumar RV. Oxidative stress in patients with epilepsy is independent of antiepileptic drugs. Seizure [Internet]. 2012;21(10):780–4. Available from: http://dx.doi.org/10.1016/j.seizure.2012.09.003

7. Nemade ST, Melinkeri RR. Oxidative and antioxidative status in epilepsy. Prevara Med Rev [Internet]. 2010;2(4):8–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19946750

8. Maes M, Supasitthumrong T, Limotai C, Michelin AP, Matsumoto AK, de Oliveira Semão L, et al. Increased oxidative stress toxicity and lowered antioxidant defenses in temporal lobe epilepsy and mesial temporal sclerosis: associations with psychiatric comorbidities. Neurobiol Mol. 2020;57(8):3334–48.

9. Nazıroğlu M, Yürekli VA. Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: Focus on trace elements. Cell Mol Neurobiol. 2013;33(5):589–99.

10. Waldbaum S, Patel M. Mitochondrial dysfunction and oxidative stress: A contributing link to acquired epilepsy? J Bioenerg Biomembr. 2010;42(6):449–55.

11. Hamed SA, Abdellah MM, El-Melegy N. Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant systems in epileptic patients. J Pharmacol Sci. 2004;96(4):465–73.

12. Nazarina N, Christijani R, Sari YD. Factors associated with plasma malondialdehyde levels in people with type 2 diabetes mellitus. J Nutrition Clinical Indonesia. 2013;9(3):139.

13. Şimşek F, Ceylan M, Aşkın S, Kızıltunç A. Serum myeloperoxidase, malondialdehyde, alpha-synuclein levels in patients with epilepsy. MNJ (Malang Neuronal Journal). 2021;7(2):93–7.

14. Arhan E, Serdaroglu A, Ozturk B, Ozturk HS, Ozcelik A, Kurt N, et al. Effects of epilepsy and antiepileptic drugs on nitric oxide, lipid peroxidation and xanthine oxidase system in children with idiopathic epilepsy. Seizure [Internet]. 2011;20(2):138–42. Available from: http://dx.doi.org/10.1016/j.seizure.2010.11.003

15. Kośmider K, Kamieniak M, Czuczwar SJ, Miziak B. Second Generation of Antiepileptic Drugs and Oxidative Stress. Int J Mol Sci. 2023;24(4).

16. Beltrán-Sarmiento E, Arregoitia-Sarabia CK, Floriano-Sánchez E, Sandoval-Pacheco R, Galván-Hernández DE, Coballase-Urrutia E, et al. Effects of valproate monotherapy on the oxidant-antioxidant status in Mexican epileptic children: A longitudinal study. Oxid Med Cell Longev. 2018;2018(3).

17. Ogunro PS, Mustapha AF, Salau AA. Lipid peroxidation and antioxidant status in patients with primary generalized epilepsy. Arch Appl Sci Res. 2013;5(1):68–74.

18. Shrivastav C, Sharma S, Parekh P. A correlative study of serum uric acid and serum malondialdehyde levels in early essential hypertension. Natl J Physiol Pharm Pharmacol. 2019;9(11):1.

19. Kumar S, Singh UN, Dhakal S. Study of oxidative stress in hypercholesterolemia. Artic Int J Contemp Med Res [Internet]. 2017;4(5):2454–7379. Available from: www.ijcmr.com

20. Budi AR, Kadri H, Asri A. Differences in malondialdehyde levels in obese and non-obese young adults. Artic Kedokt. 2017;8(Supplement 2):21–5.

21. Altoum AEA, Osman AL, Babker AMA. Impact of body mass index in malondialdehyde, antioxidant vitamins A, E, C and plasma zinc among type 2 diabetic patients. Kuwait Med J. 2019;51(1):16–20.

22. De Vecchi AF, Bamonti F, Novembrino C, Ippolito S, Guerra L, Lonati S, et al. Free and total plasma malondialdehyde in chronic renal insufficiency and in dialysis patients. Nephrol Dial Transplant. 2009;24(8):2524–9.

23. Peti A, Csiky B, Guth E, Kenyeres P, Mezosi E, Kovacs GL, et al. Effect of oxidative stress in hemodialyzed patients. Ejifcc [Internet]. 2011;22(2):45–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27683390%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4975287

24. Kaya Y, Ari E, Demir H, Soylemez N, Cebi A, Alp H, et al. Accelerated atherosclerosis in haemodialysis patients; Correlation of endothelial function with oxidative DNA damage. Nephrol Dial Transplant. 2012;27(3):1164–9.

25. Emre H, Keles M, Yildirim S, Uyanik A, Kara F, Tamer F, et al. Comparison of the oxidant-antioxidant parameters and sialic acid levels in renal transplant patients and peritoneal dialysis patients. Transplant Proc [Internet]. 2011;43(3):809–12. Available from: http://dx.doi.org/10.1016/j.transproceed.2011.01.110

26. Tigistu M, Azale T, Kebebe H, Yihunie T. Frequency of seizure attacks and associated factors among patients with epilepsy at University of Gondar Referral Hospital: A cross-sectional study, Gondar, North West Ethiopia, 2017. BMC Res Notes [Internet] . 2018;11(1):2–7. Available from: https://doi.org/10.1186/s13104-018-3761-3

27. Cramer JA, Glassman M, Rienzi V. The relationship between poor medication compliance and seizures. 2002;3:338–42.

28. Nakken KO, Solaas MH, Kjeldsen MJ, Friis ML, Pellock JM, Corey LA. Which seizure-precipitating factors do patients with epilepsy most frequently report? 2005;6:85–9.

29. Spector S, Cull C, Goldstein LH. High and low perceived self-control of epileptic seizures. 2001;42(4):556–64.

30. Kaddumukasa M, Kaddumukasa M, Matovu S, Katabira E. The frequency and precipitating factors for breakthrough seizures among patients with epilepsy in Uganda. BMC Neurol. 2013;13:182:1–7.

31. Raru TB, Geremew BM, Tamirat KS. Change in the frequency of seizure attacks and associated factors among adult epilepsy patients at Amanuel Mental Specialized Hospital (Amsh): A generalized linear mixed model (glmm). Neuropsychiatry DisTreat. 2021;17:2529–38.

32. Grewal GK, Kukal S, Kanojia N, Saso L, Kukreti S, Kukreti R. Effect of oxidative stress on ABC transporters: Contribution to epilepsy pharmacoresistance. Molecules. 2017;22(3):1–14.

33. Chalasi S, Kumar MR. Clinical profile and etiological evaluation of new onset seizures after 20 years of age. 2015;14(2):97–101.

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Published

2024-03-28

How to Cite

1.
Noegroho A, Bintoro AC, Pudjonarko D. Relationship Between Serum Malondialdehyde (MDA) Levels With Seizure Frequency In Epilepsy Patients With Combination Of Phenytoin And Valproic Acid. Medica Hospitalia J. Clin. Med. [Internet]. 2024 Mar. 28 [cited 2024 Apr. 27];11(1):38-44. Available from: http://medicahospitalia.rskariadi.co.id/medicahospitalia/index.php/mh/article/view/987

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