Reports of Biochemistry
and Molecular Biology
Sat, May 25, 2024
[Archive]
Volume 12, Issue 1 (Vol.12 No.1 Apr 2023)
rbmb.net 2023, 12(1): 147-158 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Obydah W, Fathi Abouelnaga A, Abass M, Saad S, Yehia A, Abd-Alhakem Ammar O, et al . Possible Role of Oxidative Stress and Nrf2/HO-1 Pathway in Pentylenetetrazole-induced Epilepsy in Aged Rats. rbmb.net 2023; 12 (1) :147-158
URL: http://rbmb.net/article-1-1155-en.html
URL: http://rbmb.net/article-1-1155-en.html
Walaa Obydah * 
, Ahmed Fathi Abouelnaga , Marwa Abass , Somaya Saad , Asmaa Yehia , Omar Abd-Alhakem Ammar , Alaa Mohamed Badawy , Mohie Mahmoud Ibrahim , Abdelaziz Mohamed Hussein
, Ahmed Fathi Abouelnaga , Marwa Abass , Somaya Saad , Asmaa Yehia , Omar Abd-Alhakem Ammar , Alaa Mohamed Badawy , Mohie Mahmoud Ibrahim , Abdelaziz Mohamed Hussein
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura (35516), Egypt.
Abstract: (1007 Views)
Background: To examine the impact of aging on the response of rats to pentylenetetrazole (PTZ)-induction of epilepsy and the possible role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase (HO)-1 pathway in this response.
Methods: Forty male albino rats were equally allocated into 4 groups; 1) Young control (YC) group, aged 8-12 weeks, 2) Old control (OC) group, aged 24 months, 3) PTZ-Young group: young rats received PTZ (50 mg/Kg, i.p. every other day) for 2 weeks and 4) PTZ-Old group: as group 3 but rats were old. The seizure score stage and latency to the first jerk were recorded in rats. Redox state markers in brain tissues including malondialdehyde (MDA), catalase and total antioxidant capacity (TAC) were evaluated. Also, the expression of Nrf2 and HO-1 genes were measured in the brain tissues.
Results: Old rats showed an early and a significant rise in the seizure score with PTZ administration and a significant drop in the seizure latency compared to young rats (P <0.01). Also, old rats showed a significantly higher MDA concentration and a significantly lower TAC and catalase activity than young rats (P <0.01). Moreover, the expression of Nrf2 and HO-1 was significantly lowered in old rats compared to young rats with PTZ administration (P < 0.01).
Conclusions: Aging increases the vulnerability of rats to PTZ-induced epilepsy. An effect might come down to the up-regulation of oxidative stress and the down regulation of antioxidant pathways including Nrf2 and HO-1.
Methods: Forty male albino rats were equally allocated into 4 groups; 1) Young control (YC) group, aged 8-12 weeks, 2) Old control (OC) group, aged 24 months, 3) PTZ-Young group: young rats received PTZ (50 mg/Kg, i.p. every other day) for 2 weeks and 4) PTZ-Old group: as group 3 but rats were old. The seizure score stage and latency to the first jerk were recorded in rats. Redox state markers in brain tissues including malondialdehyde (MDA), catalase and total antioxidant capacity (TAC) were evaluated. Also, the expression of Nrf2 and HO-1 genes were measured in the brain tissues.
Results: Old rats showed an early and a significant rise in the seizure score with PTZ administration and a significant drop in the seizure latency compared to young rats (P <0.01). Also, old rats showed a significantly higher MDA concentration and a significantly lower TAC and catalase activity than young rats (P <0.01). Moreover, the expression of Nrf2 and HO-1 was significantly lowered in old rats compared to young rats with PTZ administration (P < 0.01).
Conclusions: Aging increases the vulnerability of rats to PTZ-induced epilepsy. An effect might come down to the up-regulation of oxidative stress and the down regulation of antioxidant pathways including Nrf2 and HO-1.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2023/03/26 | Accepted: 2023/05/14 | Published: 2023/08/15
Received: 2023/03/26 | Accepted: 2023/05/14 | Published: 2023/08/15
References
1. Cloyd J, Hauser W, Towne A, Ramsay R, Mattson R, Gilliam F, Walczak T. Epidemiological and medical aspects of epilepsy in the elderly. Epilepsy Res. 2006;68 Suppl 1:S39-48. [DOI:10.1016/j.eplepsyres.2005.07.016] [PMID]
2. Hussain SA, Haut SR, Lipton RB, Derby C, Markowitz SY, Shinnar S. Incidence of epilepsy in a racially diverse, community-dwelling, elderly cohort: results from the Einstein aging study. Epilepsy Res. 2006;71(2-3):195-205. [DOI:10.1016/j.eplepsyres.2006.06.018] [PMID]
3. Hauser WA. Epidemiology of seizures in the elderly. In: Rowan AJ, Ramsay RE, editors. Seizures and Epilepsy in the Elderly. Oxford: Butterworth-Heinemann; 1997: 7-20.
4. DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, Garnett L, Fortner CA, Ko D. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46(4):1029-35. [DOI:10.1212/WNL.46.4.1029] [PMID]
5. Lee SK. Epilepsy in the Elderly: Treatment and Consideration of Comorbid Diseases. J Epilepsy Res. 2019;9(1):27-35.
https://doi.org/10.14581/jer.19003 [DOI:10.14581/jer.11005] [PMID] [PMCID]
6. Lowenstein DH. Pathways to discovery in epilepsy research: rethinking the quest for cures. Epilepsia. 2008;49(1):1-7. [DOI:10.1111/j.1528-1167.2007.01309.x] [PMID]
7. Martinc B, Grabnar I, Vovk T. The role of reactive species in epileptogenesis and influence of antiepileptic drug therapy on oxidative stress. Current Neuropharmacology. 2012;10(4):328-43. [DOI:10.2174/157015912804499447] [PMID] [PMCID]
8. Lugrin J, Rosenblatt-Velin N, Parapanov R, Liaudet L. The role of oxidative stress during inflammatory processes. Biological chemistry. 2014;395(2):203-30. [DOI:10.1515/hsz-2013-0241] [PMID]
9. Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nature reviews neurology. 2011;7(1):31-40. [DOI:10.1038/nrneurol.2010.178] [PMID] [PMCID]
10. Dawson R Jr, Wallace DR. Kainic acid-induced seizures in aged rats: Neurochemical correlates. Brain Res Bull. 1992;29(3-4):459-68. [DOI:10.1016/0361-9230(92)90083-A] [PMID]
11. Shetty AK, Rao MS, Hattiangady B, Zaman V, Shetty GA. Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury. J Neurosci Res. 2004;78(4):520-32. [DOI:10.1002/jnr.20302] [PMID]
12. Carmona-Aparicio L, Pérez-Cruz C, Zavala-Tecuapetla C, Granados-Rojas L, Rivera-Espinosa L, Montesinos-Correa H, et al. Overview of Nrf2 as therapeutic target in epilepsy. Int J Mol Sci. 2015;16(8):18348-67. [DOI:10.3390/ijms160818348] [PMID] [PMCID]
13. Abdelgawad, L M, Abd El-Hamed, MM, Sabry D, Abdelgwad M. Efficacy of Photobiomodulation and Metformin on Diabetic Cell Line of Human Periodontal Ligament Stem Cells through Keap1/Nrf2/Ho-1 Pathway. Rep Biochem Mol Biol. 2021;10(1):30-40. [DOI:10.52547/rbmb.10.1.30] [PMID] [PMCID]
14. Wang W, Wu Y, Zhang G, Fang H, Wang H, Zang H, et al. Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure. Brain Res. 2014;1544:54-61. [DOI:10.1016/j.brainres.2013.12.004] [PMID]
15. Chen X, Bao G, Liu F. Inhibition of USP15 Prevent Glutamate-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway in HT22 Cells. Cell Mol Neurobiol. 2020 Aug;40(6):999-1010. [DOI:10.1007/s10571-020-00789-3] [PMID]
16. El-Hefnawy MA, Yehia A, Nashar EME, Saad S, Obydah W, Alghamdi MA, et al. Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2/HO-1, IGF-1 signaling pathways cross talk. J Integr Neurosci. 2022;21(1):15. [DOI:10.31083/j.jin2101015] [PMID]
17. Hussein AM, Eldosoky M, El-Shafey M, El-Mesery M, Ali AN, Abbas KM, Abulseoud OA. Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy. Can J Physiol Pharmacol. 2019;97(1):37-46. [DOI:10.1139/cjpp-2018-0266] [PMID]
18. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972;32(3):281-94. [DOI:10.1016/0013-4694(72)90177-0] [PMID]
19. Zahran MH, Hussein AM, Barakat N, Awadalla A, Khater S, Harraz A, Shokeir AA. Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury. Int Urol Nephrol. 2015;47(11):1907-15. [DOI:10.1007/s11255-015-1099-5] [PMID]
20. Mostafa Tork O, Ahmed Rashed L, Bakr Sadek N, Abdel-Tawab MS. Targeting Altered Mitochondrial Biogenesis in the Brain of Diabetic Rats: Potential Effect of Pioglitazone and Exendin-4. Rep Biochem Mol Biol. 2019;8(3):287-300.
21. Wozniak DF, Stewart GR, Miller JP, Olney JW. Age-related sensitivity to kainate neurotoxicity. Exp Neurol. 1991;114(2):250-3. [DOI:10.1016/0014-4886(91)90042-B] [PMID]
22. Liang LP, Beaudoin ME, Fritz MJ, Fulton R, Patel M. Kainate-induced seizures, oxidative stress and neuronal loss in aging rats. Neuroscience. 2007;147(4):1114-8. [DOI:10.1016/j.neuroscience.2007.03.026] [PMID]
23. Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T. Effects of acute administration of nicotine on convulsive movements and blood levels of corticosterone in old rats. Jpn J Pharmacol. 1992 Dec;60(4):381-4. [DOI:10.1254/jjp.60.381] [PMID]
24. McCord MC, Lorenzana A, Bloom CS, Chancer ZO, Schauwecker PE. Effect of age on kainate-induced seizure severity and cell death. Neuroscience. 2008;154(3):1143-53. [DOI:10.1016/j.neuroscience.2008.03.082] [PMID] [PMCID]
25. Benkovic SA, O'Callaghan JP, Miller DB. Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice. Brain Res. 2006;1070(1):215-31. [DOI:10.1016/j.brainres.2005.11.065] [PMID]
26. Gerschman R, Gilbert D, Nye SW, Dwyer P, Fenn WO. Oxygen poisoning and X-irradiation: a mechanism in common. 1954. Nutrition. 2001;17(2):162.
27. Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int. 2015;2015:745613. [DOI:10.1155/2015/745613] [PMID] [PMCID]
28. Sharma S, Carlson S, Puttachary S, Sarkar S, Showman L, Putra M, et al. Role of the Fyn-PKCδ signaling in SE-induced neuroinflammation and epileptogenesis in experimental models of temporal lobe epilepsy. Neurobiol Dis. 2018;110:102-121. [DOI:10.1016/j.nbd.2017.11.008] [PMID] [PMCID]
29. McElroy PB, Liang LP, Day BJ, Patel M. Scavenging reactive oxygen species inhibits status epilepticus-induced neuroinflammation. Exp Neurol. 2017;298(Pt A):13-22. [DOI:10.1016/j.expneurol.2017.08.009] [PMID] [PMCID]
30. Li D, Bai X, Jiang Y, Cheng Y. Butyrate alleviates PTZ-induced mitochondrial dysfunction, oxidative stress and neuron apoptosis in mice via Keap1/Nrf2/HO-1 pathway. Brain Res Bull. 2021;168:25-35. [DOI:10.1016/j.brainresbull.2020.12.009] [PMID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
