Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6
Yıl: 2023 Cilt: 29 Sayı: 1 Sayfa Aralığı: 9 - 15 Metin Dili: İngilizce DOI: 10.4274/ArchEpilepsy.2023.22065 İndeks Tarihi: 04-06-2023
Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6
Öz: Objective: We intended to determine the vitamin B6 (Vit B6 ) protection on valproic acid (VPA)-induced liver injury. Methods: Male Sprague-Dawley rats were used. The control group: Vit B6 (50 mg/kg/day) given rats; VPA (500 mg/kg/day) given rats; VPA and Vit B6 given rats at the same dose and time for 7 days. Results: Liver glutathione and total antioxidant capacity were decreased while, lipid peroxidation, advanced oxidized protein products, tumor necrosis factor alpha, interleukin-6, nitric oxide, total oxidant status, oxidative stress index, reactive oxygen species levels and myeloperoxidase, antioxidant enzyme activities, glucose-6-phosphate dehydrogenase, and adenosine deaminase activities were increased in the VPA group. Vit B6 eased these parameters in the VPA group. In the histological determinations, nuclei including dense chromatin material, hyperemia, sinusoidal dilation, collagen accumulation in connective tissue, and large and dense granules in the cytoplasm were increased in the VPA group according to the control groups, microscopically. Conclusion: As a result, Vit B6 supplementation reversed biochemical results in VPA-induced liver damage by regulating the antioxidant status.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Kudin AP, Mawasi H, Eisenkraft A, Elger CE, Bialer M, Kunz WS. Mitochondrial liver toxicity of valproic acid and its acid derivatives is related to inhibition of α-lipoamide dehydrogenase. Int J Mol Sci. 2017;18(9):1912. [Crossref]
- 2. Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs. 2002;16(10):695-714. [Crossref]
- 3. Abdelkader NF, Elyamany M, Gad AM, Assaf N, Fawzy HM, Elesawy WH. Ellagic acid attenuates liver toxicity induced by valproic acid in rats. J Pharmacol Sci. 2020;143(1):23-29. [Crossref]
- 4. Emekli-Alturfan E, Alev B, Tunali S, et al. Effects of edaravone on cardiac damage in valproic acid induced toxicity. Ann Clin Lab Sci. 2015;45(2):166-172. [Crossref]
- 5. Oztay F, Tunali S, Kayalar O, Yanardag R. The protective effect of vitamin U on valproic acid-induced lung toxicity in rats via amelioration of oxidative stress. J Biochem Mol Toxicol. 2020;34(12):e22602. doi: 10.1002/jbt.22602. [Crossref]
- 6. Walker CP, Deb S. Rhabdomyolysis and hepatotoxicity from valproic acid: Case reports. J Pharm Pract. 2021;34(4):648-652. [Crossref]
- 7. Vidaurre J, Gedela S, Yarosz S. Antiepileptic drugs and liver disease. Pediatr Neurol. 2017;77:23-36. [Crossref]
- 8. Jafarian I, Eskandari MR, Mashayekhi V, Ahadpour M, Hosseini MJ. Toxicity of valproic acid in isolated rat liver mitochondria. Toxicol Mech Methods. 2013;23(8):617-623. [Crossref]
- 9. Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: a review. J Appl Pharm Sci. 2012;2:233-243. [Crossref]
- 10. Sokmen BB, Tunali S, Yanardag R. Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats. Food Chem Toxicol. 2012;50(10):3562-3566. [Crossref]
- 11. Tunali S, Cimen ES, Yanardag R. The effects of chard on brain damage in valproic acid-induced toxicity. J Food Biochem. 2020:e13382. [Crossref]
- 12. Ueland PM, McCann A, Midttun Ø, Ulvik A. Inflammation, vitamin B6 and related pathways. Mol Aspects Med. 2017;53:10-27. [Crossref]
- 13. Hellmann H, Mooney S. Vitamin B6 : a molecule for human health? Molecules. 2010;15(1):442-459. [Crossref]
- 14. Turkyilmaz IB, Altas N, Arisan I, Yanardag R. Effect of vitamin B6 on brain damage in valproic acid induced toxicity. J Biochem Mol Toxicol. 2021;35(9):e22855. [Crossref]
- 15. Tunali S. The effects of vitamin B6 on lens antioxidant system in valproic acid-administered rats. Hum Exp Toxicol. 2014;33(6):623-628. [Crossref]
- 16. Beutler E. Glutathione in red cell metabolism, A Manual of Biochemical Methods. In: Grune, Stratton. 1975:112-114. [Crossref]
- 17. Ledwozyw A, Michalak J, Stepień A, Kadziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta. 1986;155(3):275- 283. [Crossref]
- 18. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996;49(5):1304-1313. [Crossref]
- 19. Wei H, Frenkel K. In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. Cancer Res. 1991;51(16):4443-4449. [Crossref]
- 20. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5(1):62-71. [Crossref]
- 21. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277-285. [Crossref]
- 22. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-1111. [Crossref]
- 23. Zhang Y, Chen J, Ji H, Xiao ZG, Shen P, Xu LH. Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model. BMC Complement Altern Med. 2018;18(1):343. [Crossref]
- 24. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-126. [Crossref]
- 25. Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986;82(3):512-520. [Crossref]
- 26. Wendel A. Glutathione peroxidase. Methods Enzymol. 1981;77:325-333. [Crossref]
- 27. Beutler E. Red cell metabolism, A Manual of Biochemical Methods, 12th Academic Press. 1971:68-80. [Crossref]
- 28. Beutler E. Red cell metabolism. In: A Manual of Biochemical Methods. 1984:74-76. [Crossref]
- 29. Karker H. Method for estimation of serum adenosine deaminase. Scand J Clin Lab Invest. 1964;16:570-574. [Crossref]
- 30. Berger I, Segal I, Shmueli D, Saada A. The effect of antiepileptic drugs on mitochondrial activity: a pilot study. J Child Neurol. 2010;25(5):541-545. [Crossref]
- 31. Sujol G, Docquier A, Boulahtouf A, Castet-Nicolas A, Cavaillès V. Vitamine B6 et cancer: des données cliniques aux mécanismes moléculaires [Vitamin B6 and cancer: from clinical data to molecularly mechanisms]. Bull Cancer. 2011;98(10):1201-1208. [Crossref]
- 32. Kiang TK, Teng XW, Karagiozov S, Surendradoss J, Chang TK, Abbott FS. Role of oxidative metabolism in the effect of valproic acid on markers of cell viability, necrosis, and oxidative stress in sandwich-cultured rat hepatocytes. Toxicol Sci. 2010;118(2):501-509. [Crossref] 33. Hsu CC, Cheng CH, Hsu CL, Lee WJ, Huang SC, Huang YC. Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress. Food Nutr Res. 2015;59:25702. [Crossref] 34. Tong V, Teng XW, Chang TK, Abbott FS. Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats. Toxicol Sci. 2005;86(2):427-435. [Crossref] 35. Chaudhary S, Ganjoo P, Raiusddin S, Parvez S. Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. Protoplasma. 2015;252(1):209-217. [Crossref] 36. Giustina AD, Danielski LG, Novochadlo MM, et al. Vitamin B6 reduces oxidative stress in lungs and liver in experimental sepsis. An Acad Bras Cienc. 2019;91(4):e20190434. [Crossref] 37. Neuman MG, Nanau RM, Shekh-Ahmad T, Yagen B, Bialer M. Valproic acid derivatives signal for apoptosis and repair in vitro. Clin Biochem. 2013;46(15):1532-1537. [Crossref] 38. Nanau RM, Neuman MG. Adverse drug reactions induced by valproic acid. Clin Biochem. 2013;46(15):1323-1338. [Crossref] 39. Oztopuz O, Turkon H, Buyuk B, et al. Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. Mol Biol Rep. 2020;47(1):317- 325. [Crossref] 40. Anatoliotakis N, Deftereos S, Bouras G, et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem. 2013;13(2):115-138. [Crossref] 41. Li J, Billiar TR. Nitric Oxide. IV. Determinants of nitric oxide protection and toxicity in liver. Am J Physiol. 1999;276(5):G1069-1073. [Crossref] 42. Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59(3):583-594. [Crossref] 43. Nazmy EA, El-Khouly OA, Atef H, Said E. Sulforaphane protects against sodium valproate-induced acute liver injury. Can J Physiol Pharmacol. 2017;95(4):420-426. [Crossref] 44. Turkyilmaz IB, Bilgin Sokmen B, Yanardag R. Alpha-lipoic acid prevents brain injury in rats administered with valproic acid. J Biochem Mol Toxicol. 2020;34(11):e22580. [Crossref] 45. Morris MS, Sakakeeny L, Jacques PF, Picciano MF, Selhub J. Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr. 2010;140(1):103-110. [Crossref] 46. Pourahmad J, Eskandari MR, Kaghazi A, Shaki F, Shahraki J, Fard JK. A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. Toxicol In Vitro. 2012;26(4):545-551. [Crossref] 47. Salsaa M, Pereira B, Liu J, et al. Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae. Sci Rep. 2020;10(1):11785. [Crossref] 48. Yang HC, Wu YH, Yen WC, Liu HY, Hwang TL, Stern A, Chiu DT. The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer. Cells. 2019;8(9):1055. [Crossref] 49. Torres S, Baulies A, Insausti-Urkia N, et al. Endoplasmic Reticulum Stress Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure. Gastroenterology. 2019;157(2):552-568. [Crossref] 50. Shabbir M, Afsar T, Razak S, Almajwal A, Khan MR. Phytochemical analysis and Evaluation of hepatoprotective effect of Maytenus royleanus leaves extract against anti-tuberculosis drug induced liver injury in mice. Lipids Health Dis. 2020;19(1):46. [Crossref]
| APA | Turkyilmaz I, Karatug Kacar A, Bolkent S, YANARDAG R (2023). Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. , 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| Chicago | Turkyilmaz Ismet Burcu,Karatug Kacar Ayse,Bolkent Sehnaz,YANARDAG REFIYE Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. (2023): 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| MLA | Turkyilmaz Ismet Burcu,Karatug Kacar Ayse,Bolkent Sehnaz,YANARDAG REFIYE Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. , 2023, ss.9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| AMA | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. . 2023; 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| Vancouver | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. . 2023; 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| IEEE | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R "Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6." , ss.9 - 15, 2023. 10.4274/ArchEpilepsy.2023.22065 |
| ISNAD | Turkyilmaz, Ismet Burcu vd. "Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6". (2023), 9-15. https://doi.org/10.4274/ArchEpilepsy.2023.22065 |
| APA | Turkyilmaz I, Karatug Kacar A, Bolkent S, YANARDAG R (2023). Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. Archives of epilepsy (Online), 29(1), 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| Chicago | Turkyilmaz Ismet Burcu,Karatug Kacar Ayse,Bolkent Sehnaz,YANARDAG REFIYE Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. Archives of epilepsy (Online) 29, no.1 (2023): 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| MLA | Turkyilmaz Ismet Burcu,Karatug Kacar Ayse,Bolkent Sehnaz,YANARDAG REFIYE Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. Archives of epilepsy (Online), vol.29, no.1, 2023, ss.9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| AMA | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. Archives of epilepsy (Online). 2023; 29(1): 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| Vancouver | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6. Archives of epilepsy (Online). 2023; 29(1): 9 - 15. 10.4274/ArchEpilepsy.2023.22065 |
| IEEE | Turkyilmaz I,Karatug Kacar A,Bolkent S,YANARDAG R "Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6." Archives of epilepsy (Online), 29, ss.9 - 15, 2023. 10.4274/ArchEpilepsy.2023.22065 |
| ISNAD | Turkyilmaz, Ismet Burcu vd. "Damage to Liver Tissue Caused by Valproic Acid Used for Treating Epilepsy: Protective Effects of Vitamin B6". Archives of epilepsy (Online) 29/1 (2023), 9-15. https://doi.org/10.4274/ArchEpilepsy.2023.22065 |
