Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture
Abstract
Objective: Epilepsy is a common brain
disorder that seizures could cause neuronal loss in the hippocampus. Oxidative
stress has an important role in the pathology of this way. The aim of this
study was to investigate the neuroprotective effect of astaxanthin (ATX), on
pentylenetetrazole (PTZ) induced epileptic seizures in rats and in SH-SY5Y human
neuroblastoma cell culture.
Method: In our study, we used 42 male 230-250 g Wistar
Albino rats. Animals were divided into seven groups as control, saline (PTZ; 1
ml/kg serum physiologic), positive control (2,5 mg/kg diazepam), 10 mg/kg, 20
mg/kg, 40 mg/kg and 80 mg/kg ATX for seven days. Thirty min after the
administration of the last drug at the indicated doses, PTZ was administered 45
mg/kg to induce an epileptic seizure. The animals were observed for 30 min.
Seizure stages according to the Racine Scale (RC) and first myoclonic jerk
times (FMJ). Twenty four hours after PTZ injection, passive avoidance test was
performed, and then brain tissues were removed for biochemical and
histopathological evaluation. The hippocampal Cornu Ammonis 1 (CA1), CA3 and
dentate gyrus (DG) regions were evaluated histopathologically regarding
neuronal damage. Besides, oxidative stress markers total antioxidant status
(TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were
measured in brain tissues. Furthermore, ATX was performed in vitro SH-SY5Y human neuroblastoma cell
culture to
evaluate PTZ-induced neurotoxicity.
Results: When epileptic behaviors were evaluated, ATX did not affect RC and FMJ (p>0,
05). However, ATX reduced both cognitive impairment in passive avoidance test
and neuronal damage in the hippocampus (p<0, 05). Moreover, ATX reduced both
TOS levels and OSI in the brain (p<0, 05). Besides of these in vitro
studies, ATX increased neuronal viability in vitro.
Conclusions: Although
ATX does not have antiepileptic properties directly, it has a protective effect
on not only in vivo but also in vitro. These effects may occur by possible
oxidative pathways.
References
- 1. El-Hagrassy MM, Texeira-Santos AC, Fregni F. Epilepsy. Neuromethods. 2018;138(May):445–517.
- 2. Pearson-Smith JN, Patel M. Metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci. 2017;18(11):1–13.
- 3. Ryvlin P, Rheims S. Predicting epilepsy surgery outcome. Curr Opin Neurol. 2016;29(2):182–8.
- 4. Güvenç C, Dupont P, Van den Stock J, Seynaeve L, Porke K, Dries E, et al. Correlation of neuropsychological and metabolic changes after epilepsy surgery in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis. EJNMMI Res. EJNMMI Research; 2018;8.
- 5. Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int. 2015;2015.
- 6. Taskıran AS, Gumus E, Gunes H, Cetindag A, Ozdemir E. The Protective Effects of Vitamin B 12 on Pentylenetetrazole-Induced Seizures in Rats. Anat Physiol Biochem Int J. 2018;4(1):1–5.
- 7. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int [Internet]. Elsevier B.V.; 2011;59(2):122–37. Available from: http://dx.doi.org/10.1016/j.neuint.2011.03.025.
- 8. Sawicka-Glazer E, Czuczwar SJ. Vitamin C: A new auxiliary treatment of epilepsy? Pharmacol Reports [Internet]. Institute of Pharmacology, Polish Academy of Sciences; 2014;66(4):529–33. Available from: http://dx.doi.org/10.1016/j.pharep.2014.02.016.
- 9. González-Ramírez M, Razo-Juárez LI, Sauer-Ramírez JL, González-Trujano ME, Salgado-Ceballos H, Orozco-Suarez S. Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in immature rats. Pharmacol Biochem Behav [Internet]. Elsevier B.V.; 2010;97(2):267–72. Available from: http://dx.doi.org/10.1016/j.pbb.2010.08.009.
- 10. Journal W, Pharmacypharmaceutical OF, Patil S. the Neuroprotective Effect of Α - Tocopherol on Ptz-Induced Epilepsy Causes Oxidative Stress and ... 2017;6(June):1124–40.
- 11. Bhuvaneswari S, Arunkumar E, Viswanathan P, Anuradha CV. Astaxanthin restricts weight gain, promotes insulin sensitivity and curtails fatty liver disease in mice fed a obesity-promoting diet. Process Biochem [Internet]. Elsevier Ltd; 2010;45(8):1406–14. Available from: http://dx.doi.org/10.1016/j.procbio.2010.05.016.
- 12. Leite MF, De Lima A, Massuyama MM, Otton R. In vivo astaxanthin treatment partially prevents antioxidant alterations in dental pulp from alloxan-induced diabetic rats. Int Endod J. 2010;43(11):959–67.
- 13. Elmer R, Chen J-T, Kotani K. Astaxanthin as a Potential Protector of Liver Function: A Review. J Clin Med Res [Internet]. 2016;8(10):701–4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012237/pdf/jocmr-08-701.pdf.
- 14. Zhang XS, Zhang X, Wu Q, Li W, Wang CX, Xie G Bin, et al. Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage. J Surg Res. 2014;192(1):206–13.
- 15. Pan L, Zhou Y, Li X fang, Wan Q jia, Yu L hua. Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats. Brain Res Bull [Internet]. Elsevier Inc.; 2017;130:211–20. Available from: http://dx.doi.org/10.1016/j.brainresbull.2017.01.024.
- 16. Chang Y, Lu CW, Chen YJ, Lin TY, Huang SK, Wang SJ. Astaxanthin protects against kainic acid-induced seizures and pathological consequences. Neurochem Int [Internet]. Elsevier Ltd; 2018;116:85–94. Available from: https://doi.org/10.1016/j.neuint.2018.02.008.
- 17. Shen H, Kuo C-C, Chou J, Delvolve A, Jackson SN, Post J, et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J [Internet]. 2009;23(6):1958–68. Available from: http://www.fasebj.org/cgi/doi/10.1096/fj.08-123281.
- 18. Lu YP, Liu SY, Sun H, Wu XM, Li JJ, Zhu L. Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res [Internet]. Elsevier B.V.; 2010;1360:40–8. Available from: http://dx.doi.org/10.1016/j.brainres.2010.09.016.
- 19. Pohlmann-Eden B, Aldenkamp A, Baker GA, Brandt C, Cendes F, Coras R, et al. The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding. Epilepsy Behav [Internet]. Elsevier Inc.; 2015;51:199–209. Available from: http://dx.doi.org/10.1016/j.yebeh.2015.07.005.
- 20. Scott AJ, Sharpe L, Thayer Z, Miller LA, Wong T, Parratt K, et al. A qualitative examination and theoretical model of anxiety in adults with epilepsy. Epilepsy Behav [Internet]. Elsevier Inc.; 2018;85:95–104. Available from: https://doi.org/10.1016/j.yebeh.2018.05.023.
- 21. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Longev. 2014;2014.
- 22. Lu Y, Xie T, He XX, Mao ZF, Jia LJ, Wang WP, et al. Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus. Neurosci Lett [Internet]. Elsevier Ireland Ltd; 2015;597:49–53. Available from: http://dx.doi.org/10.1016/j.neulet.2015.04.018.
- 23. Zhou X, Zhang F, Hu X, Chen J, Wen X, Sun Y, et al. Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice. Physiol Behav. 2015;151:412–20.
- 24. Lee D-H, Lee YJ, Kwon KH. Neuroprotective Effects of Astaxanthin in Oxygen-Glucose Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat. J Clin Biochem Nutr [Internet]. 2010;47(2):121–9. Available from: http://joi.jlc.jst.go.jp/JST.JSTAGE/jcbn/10-29?from=CrossRef.
- 25. Lobos P, Bruna B, Cordova A, Barattini P, Galáz JL, Adasme T, et al. Astaxanthin protects primary hippocampal neurons against noxious effects of A β-oligomers. Neural Plast. 2016;2016.
- 26. Yuki Manabe, Toshiyuki Komatsu, Shinobu Seki & Tatsuya Sugawara. Dietary astaxanthin can accumulate in the brain of rats. Bioscience, Biotechnology, and Biochemistry,2018; 82:8, 1433-1436, DOI: 10.1080/09168451.2018.1459467.
- 27. Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs. 2015;13(9):5750–66.
Astaksantin’in (ATX) ratlarda oluşturulan PTZ ile indüklenmiş epileptik nöbetlerde oluşan bilişsel bozukluğa karşı ve insan SH-SY5Y nöroblastoma hücre kültüründe PTZ ile indüklenen nörotoksisiteye karşı nöroprotektif etkisi
Abstract
Amaç: Epilepsi, nöbet sonrası hipokampusta
nöronal kayba neden olduğu bilinen yaygın bir beyin hastalığıdır. Oksidatif
stres bu patolojide önemli bir yere
sahiptir. Bu çalışmanın amacı, astaksantinin (ATX), ratlarda pentilenetrazol
(PTZ) ile indüklenen epileptik nöbetlerde nöroprotektif etkisininin
araştırılması ve ATX ’in SH-SY5Y insan
nöroblastoma hücre kültüründe PTZ ile indüklenen nörotoksisite üzerine etkisini
araştırmaktır.
Yöntem: Çalışmamızda 42 adet 230-250 gr Wistar
Albino cinsi erkek rat kullandık. Hayvanlar kontrol, salin (PTZ; 1 ml / kg
serum fizyolojik), pozitif kontrol (2,5 mg / kg diazepam), 7 gün boyunca 10 mg
/ kg, 20 mg / kg, 40 mg / kg ve 80 mg ATX verilen olarak yedi gruba ayrıldı.
Son ilacın belirtilen dozlarda uygulanmasından otuz dakika sonra, epileptik
nöbeti indüklemek için PTZ 45 mg / kg uygulandı. Hayvanlar 30 dakika gözlendi.
Racine Scale (RC) ve ilk miyoklonik jerk zamanlarına (FMJ) göre nöbet aşamaları
kayıt edildi. Ratlara PTZ enjeksiyonundan yirmi dört saat sonra pasif kaçınma
testi yapıldı ve daha sonra biyokimyasal ve histopatolojik değerlendirme için
beyin dokuları çıkarıldı. Hipokampal Cornu Ammonis 1 (CA1), CA3 ve dentat girus
(DG) bölgeleri, nöronal hasar açısından histopatolojik olarak değerlendirildi.
Ayrıca, beyin dokularında oksidatif stres belirteçleri total antioksidan status
(TAS), total oksidan status (TOS) ve oksidatif stres indeksi (OSI)) ölçüldü.
Ayrıca ATX’ in PTZ'nin neden olduğu nörotoksisiteye olan etkisini
değerlendirmek için in vitro SH-SY5Y insan nöroblastoma hücre kültürü
gerçekleştirildi.
Bulgular:
Epileptik davranışlar değerlendirildiğinde, ATX, RC
ve FMJ'yi etkilememiştir (p> 0, 05). Bununla birlikte, ATX hem pasif kaçınma
testinde bilişsel bozulmayı hem de hipokampüsteki nöronal hasarı azaltmıştır (p
<0, 05). Ayrıca, ATX beyindeki hem TOS düzeylerini hem de OSI'yi düşürmüştür
(p <0, 05). İn vitro SH-SY5Y insan nöroblastoma hücre kültüründe ATX’ in in
vitro nöronal canlılığı arttırdığı tesbit edildi.
Sonuç: Her ne kadar ATX doğrudan
antiepileptik özelliklere sahip olmasa da, sadece in vivo olarak değil in vitro
olarak da nöroprotektif bir etkiye sahiptir. Bu etkilerin olası oksidatif
yolaklarla oluşabileceği düşünülmektedir.
References
- 1. El-Hagrassy MM, Texeira-Santos AC, Fregni F. Epilepsy. Neuromethods. 2018;138(May):445–517.
- 2. Pearson-Smith JN, Patel M. Metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci. 2017;18(11):1–13.
- 3. Ryvlin P, Rheims S. Predicting epilepsy surgery outcome. Curr Opin Neurol. 2016;29(2):182–8.
- 4. Güvenç C, Dupont P, Van den Stock J, Seynaeve L, Porke K, Dries E, et al. Correlation of neuropsychological and metabolic changes after epilepsy surgery in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis. EJNMMI Res. EJNMMI Research; 2018;8.
- 5. Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int. 2015;2015.
- 6. Taskıran AS, Gumus E, Gunes H, Cetindag A, Ozdemir E. The Protective Effects of Vitamin B 12 on Pentylenetetrazole-Induced Seizures in Rats. Anat Physiol Biochem Int J. 2018;4(1):1–5.
- 7. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int [Internet]. Elsevier B.V.; 2011;59(2):122–37. Available from: http://dx.doi.org/10.1016/j.neuint.2011.03.025.
- 8. Sawicka-Glazer E, Czuczwar SJ. Vitamin C: A new auxiliary treatment of epilepsy? Pharmacol Reports [Internet]. Institute of Pharmacology, Polish Academy of Sciences; 2014;66(4):529–33. Available from: http://dx.doi.org/10.1016/j.pharep.2014.02.016.
- 9. González-Ramírez M, Razo-Juárez LI, Sauer-Ramírez JL, González-Trujano ME, Salgado-Ceballos H, Orozco-Suarez S. Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in immature rats. Pharmacol Biochem Behav [Internet]. Elsevier B.V.; 2010;97(2):267–72. Available from: http://dx.doi.org/10.1016/j.pbb.2010.08.009.
- 10. Journal W, Pharmacypharmaceutical OF, Patil S. the Neuroprotective Effect of Α - Tocopherol on Ptz-Induced Epilepsy Causes Oxidative Stress and ... 2017;6(June):1124–40.
- 11. Bhuvaneswari S, Arunkumar E, Viswanathan P, Anuradha CV. Astaxanthin restricts weight gain, promotes insulin sensitivity and curtails fatty liver disease in mice fed a obesity-promoting diet. Process Biochem [Internet]. Elsevier Ltd; 2010;45(8):1406–14. Available from: http://dx.doi.org/10.1016/j.procbio.2010.05.016.
- 12. Leite MF, De Lima A, Massuyama MM, Otton R. In vivo astaxanthin treatment partially prevents antioxidant alterations in dental pulp from alloxan-induced diabetic rats. Int Endod J. 2010;43(11):959–67.
- 13. Elmer R, Chen J-T, Kotani K. Astaxanthin as a Potential Protector of Liver Function: A Review. J Clin Med Res [Internet]. 2016;8(10):701–4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012237/pdf/jocmr-08-701.pdf.
- 14. Zhang XS, Zhang X, Wu Q, Li W, Wang CX, Xie G Bin, et al. Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage. J Surg Res. 2014;192(1):206–13.
- 15. Pan L, Zhou Y, Li X fang, Wan Q jia, Yu L hua. Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats. Brain Res Bull [Internet]. Elsevier Inc.; 2017;130:211–20. Available from: http://dx.doi.org/10.1016/j.brainresbull.2017.01.024.
- 16. Chang Y, Lu CW, Chen YJ, Lin TY, Huang SK, Wang SJ. Astaxanthin protects against kainic acid-induced seizures and pathological consequences. Neurochem Int [Internet]. Elsevier Ltd; 2018;116:85–94. Available from: https://doi.org/10.1016/j.neuint.2018.02.008.
- 17. Shen H, Kuo C-C, Chou J, Delvolve A, Jackson SN, Post J, et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J [Internet]. 2009;23(6):1958–68. Available from: http://www.fasebj.org/cgi/doi/10.1096/fj.08-123281.
- 18. Lu YP, Liu SY, Sun H, Wu XM, Li JJ, Zhu L. Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res [Internet]. Elsevier B.V.; 2010;1360:40–8. Available from: http://dx.doi.org/10.1016/j.brainres.2010.09.016.
- 19. Pohlmann-Eden B, Aldenkamp A, Baker GA, Brandt C, Cendes F, Coras R, et al. The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding. Epilepsy Behav [Internet]. Elsevier Inc.; 2015;51:199–209. Available from: http://dx.doi.org/10.1016/j.yebeh.2015.07.005.
- 20. Scott AJ, Sharpe L, Thayer Z, Miller LA, Wong T, Parratt K, et al. A qualitative examination and theoretical model of anxiety in adults with epilepsy. Epilepsy Behav [Internet]. Elsevier Inc.; 2018;85:95–104. Available from: https://doi.org/10.1016/j.yebeh.2018.05.023.
- 21. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Longev. 2014;2014.
- 22. Lu Y, Xie T, He XX, Mao ZF, Jia LJ, Wang WP, et al. Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus. Neurosci Lett [Internet]. Elsevier Ireland Ltd; 2015;597:49–53. Available from: http://dx.doi.org/10.1016/j.neulet.2015.04.018.
- 23. Zhou X, Zhang F, Hu X, Chen J, Wen X, Sun Y, et al. Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice. Physiol Behav. 2015;151:412–20.
- 24. Lee D-H, Lee YJ, Kwon KH. Neuroprotective Effects of Astaxanthin in Oxygen-Glucose Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat. J Clin Biochem Nutr [Internet]. 2010;47(2):121–9. Available from: http://joi.jlc.jst.go.jp/JST.JSTAGE/jcbn/10-29?from=CrossRef.
- 25. Lobos P, Bruna B, Cordova A, Barattini P, Galáz JL, Adasme T, et al. Astaxanthin protects primary hippocampal neurons against noxious effects of A β-oligomers. Neural Plast. 2016;2016.
- 26. Yuki Manabe, Toshiyuki Komatsu, Shinobu Seki & Tatsuya Sugawara. Dietary astaxanthin can accumulate in the brain of rats. Bioscience, Biotechnology, and Biochemistry,2018; 82:8, 1433-1436, DOI: 10.1080/09168451.2018.1459467.
- 27. Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs. 2015;13(9):5750–66.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Surgical Science Research Articles |
| Authors | |
| Publication Date | March 28, 2019 |
| Acceptance Date | March 26, 2019 |
| Published in Issue | Year 2019 |