Selenyumun sıçan hipokampusunda cisplatin kaynaklı oksidatif hasara karşı nöroprotektif etkileri

Öz

Amaç: Bu çalışma, selenyumun cisplatin kaynaklı merkezi sinir sistemi nörotoksisitesine karşı potansiyel bir nöroprotektif ajan olarak rolünü değerlendirmek amacıyla, oksidatif stresin hipokampüsteki rolüyle birlikte bilişsel ve davranışsal etkileri kapsamlı bir şekilde değerlendirmeyi amaçlamıştır. Gereç ve yöntem: Otuz sekiz erkek sıçan kontrol, sisplatin, selenyum ve sisplatin+selenyum grublarına ayrıldı. Sıçanlara tek doz sisplatin (7,5 mg/kg) intraperitoneal olarak uygulandı. Selenyum (1 mg/kg) 21 gün boyunca günde bir kez oral yoldan gavaj yoluyla uygulandı. Kısa süreli hafızayı (KSH) ve uzun süreli hafızayı (USH) test etmek için yeni konum ve nesne tanıma testleri kullanıldı. Depresyon düzeyini ölçmek için zorunlu yüzme testi kullanıldı. Toplam antioksidan durumu (TAS), süper oksidaz dismutaz (SOD), toplam oksidan durumu (TOS) ve malondialdehit (MDA), ELISA yöntemi kullanılarak hipokampüs dokusundan ölçüldü. Bulgular: Cisplatin tedavisi sıçanlarda kilo kaybına neden oldu p=0,001. Cisplatin grubunda kontrol grubuna göre TOS p=0,02 ve MDA p=0,05 seviyelerinde artış, TAS p=0,03 ve SOD p=0,01 seviyelerinde azalma görüldü. Cisplatin+Selenyum grubunda bu oksidatif hasar parametrelerinde kontrol grubuna kıyasla istatistiksel olarak anlamlı bir değişiklik gözlenmedi. Cisplatin grubunda KSH ve USH'de bozulma görüldü p=0,05. Ancak Cisplatin+Selenyum grubunda USH'daki bozulmada bir miktar iyileşme görüldü. Cisplatin grubunda, kontrol grubuna kıyasla depresyon düzeyinde artış gözlemlenirken, Cisplatin+Selenyum grubunda önemli ölçüde azaldı p=0,001. Sonuç: Elde edilen bulgular, selenyum takviyesinin sıçanlarda cisplatin kaynaklı merkezi sinir sisteminde nörotoksik etkilerin hafifletilmesinde potansiyel terapötik bir rol oynayabileceğini düşündürmektedir.

Anahtar Kelimeler

• Hipokampus
• selenyum
• oksidatif stres
• davranışsal test

Neuroprotective effects of selenium against cisplatin-induced oxidative damage in the rat hippocampus

Abstract

Purpose: This study aimed to comprehensively evaluate the cognitive and behavioral effects together with the role of oxidative stress in the hippocampus in order to evaluate the role of selenium as a potential neuroprotective agent against cisplatin-induced central nervous system neurotoxicity. Materials and methods: Thirty-eight male rats were divided into control, cisplatin, selenium, and cisplatin+selenium groups. A single dose of cisplatin (7.5 mg/kg) was administered intraperitoneally to the rats. Selenium (1 mg/kg) was administered orally once daily by gavage for 21 days. Novel location and object recognition tests were used to test short-term memory (STM) and long-term memory (LTM). The forced swim test was used to measure depression level. Total antioxidant status (TAS), superoxide dismutase (SOD), total oxidant status (TOS), and malondialdehyde (MDA) were measured in hippocampus tissue using the ELISA method. Results: Cisplatin treatment caused weight loss in rats p=0.001. TOS p=0.02 and MDA p=0.05 levels increased, and TAS p=0.03 and SOD p=0.01 levels decreased in the cisplatin group compared to the control group. No statistically significant change was observed in these oxidative damage parameters in the cisplatin+selenium group compared to the control group. STM and LTM were impaired in the cisplatin group p=0.05. However, some improvement was observed in the LTM impairment in the Cisplatin+selenium group. While depression levels increased in the cisplatin group compared to the control group, they were significantly reduced in the Cisplatin+selenium group p=0.001. Conclusion: The findings suggest that selenium supplementation may play a potential therapeutic role in alleviating cisplatin-induced neurotoxic effects in the central nervous system in rats.

Keywords

• Hippocampus
• selenium
• oxidative stress
• behavioral test

Kaynakça

1. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88:102925. doi:10.1016/j.bioorg.2019.102925
2. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364-378. doi:10.1016/j.ejphar.2014.07.025
3. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73(9):994-1007. doi:10.1038/sj.ki.5002786
4. Desilets A, Adam JP, Soulières D. Management of cisplatin-associated toxicities in bladder cancer patients. Curr Opin Support Palliat Care. 2020;14(3):286-292. doi:10.1097/spc.0000000000000505
5. Hakiminia B, Goudarzi A, Moghaddas A. Has vitamin E any shreds of evidence in cisplatin-induced toxicity. J Biochem Mol Toxicol. 2019;33(8):e22349. doi:10.1002/jbt.22349
6. Naik AK, Tandan SK, Dudhgaonkar SP, et al. Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats. Eur J Pain. 2006;10(7):573-579. doi:10.1016/j.ejpain.2005.08.006
7. Wang LJ, Zhang HW, Zhou JY, et al. Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet. J Nutr Biochem. 2014;25(3):329-336. doi:10.1016/j.jnutbio.2013.11.007
8. Avery JC, Hoffmann PR. Selenium, selenoproteins, and immunity. Nutrients. 2018;10(9):1203. doi:10.3390/nu10091203

9. Karavelioglu E, Boyaci MG, Simsek N, et al. Selenium protects cerebral cells by cisplatin induced neurotoxicity. Acta Cir Bras. 2015;30(6):394-400. doi:10.1590/s0102-865020150060000004
10. Vukovic R, Selakovic D, Stankovic JSK, Kumburovic I, Jovicic N, Rosic G. Alteration of Oxidative stress and apoptotic markers alterations in the rat prefrontal cortex influence behavioral response induced by cisplatin and N-acetylcysteine in the tail suspension test. J Integr Neurosci. 2021;20(3):711-718. doi:10.31083/j.jin2003076
11. Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2000;57(13-14):1825-35. doi:10.1007/pl00000664
12. Kim SH, Johnson VJ, Shin TY, Sharma RP. Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways. Experimental biology and medicine (Maywood, NJ). 2004;229(2):203-13. doi:10.1177/153537020422900209
13. Sanmartín C, Plano D, Sharma AK, Palop JA. Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy. Int J Mol Sci. 2012;13(8):9649-9672. doi:10.3390/ijms13089649
14. Janelsins MC, Kohli S, Mohile SG, Usuki K, Ahles TA, Morrow GR. An update on cancer-and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38(3):431-438. doi:10.1053/j.seminoncol.2011.03.014
15. Miedel CJ, Patton JM, Miedel AN, Miedel ES, Levenson JM. Assessment of spontaneous alternation, novel object recognition and limb clasping in transgenic mouse models of amyloid-β and tau neuropathology. J Vis Exp. 2017;(123):e55523. doi:10.3791/55523
16. Bromley Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. J Vis Exp. 2011;20(53):2920. doi:10.3791/2920
17. Uzunok B, Kahveci N, Güleç G. Sıçanlarda zorunlu yüzme testi ile oluşturulan depresyon modelinde nitrik oksitin rolü. Uludağ Tıp Fakültesi Dergisi. 2010;36(1):23-28.
18. Abdel Wahab WM, Moussa FI. Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation. Drug Des Devel Ther. 2019;13:1155-1162. doi:10.2147/dddt.S191240
19. Antunes LMG, Darin JDAC, Maria de Lourdes PB. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res. 2001;43(2):145-150. doi:10.1006/phrs.2000.0724
20. Kumburovic I, Selakovic D, Juric T, et al. Antioxidant effects of satureja hortensis l. attenuate the anxiogenic effect of cisplatin in rats. Oxid Med Cell Longev. 2019;2019:8307196. doi:10.1155/2019/8307196
21. Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res. 1988;31(1):47-59. doi:10.1016/0166-4328(88)90157-x
22. Wu C, Yang L, Li Y, et al. Effects of exercise training on anxious-depressive-like behavior in alzheimer rat. Med Sci Sports Exerc. 2020;52(7):1456-1469. doi:10.1249/mss.0000000000002294
23. Altunkaya M. Öğrenme ve bellek deneylerinde deney hayvanlarına yaklaşım ve deney modellerinin değerlendirilmesi. Harran Üniversitesi Tıp Fakültesi Dergisi. 2024;21(3):547-556. doi:10.35440/hutfd.1487260
24. Küçükkarapınar M, Dönmez A, Candansayar S, et al. Erken dönem müdahalelerin erişkin wistar sıçanlarında davranışsal ve nörogelişimsel etkileri. Arch Neuropsychiatry. 2020;58(2):137-145. doi:10.29399/npa.24943
25. Garcia JM, Scherer T, Chen Ja, et al. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology. 2013;154(9):3118-3129. doi:10.1210/en.2013-1179
26. Vera G, Chiarlone A, Martín MI, Abalo R. Altered feeding behaviour induced by long-term cisplatin in rats. Auton Neurosci. 2006;126:81-92. doi:10.1016/j.autneu.2006.02.011
27. Liu YL, Malik NM, Sanger GJ, Andrews PLR. Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents. Cancer Chemother Pharmacol. 2006;58(3):326-333. doi:10.1007/s00280-005-0179-0
28. Lin MT, Ko JL, Liu TC, Chao PT, Ou CC. Protective effect of D-methionine on body weight loss, anorexia, and nephrotoxicity in cisplatin-induced chronic toxicity in rats. Integr Cancer Ther. 2018;17(3):813-824. doi:10.1177/1534735417753543
29. Kempermann G, Wiskott L, Gage FH. Functional significance of adult neurogenesis. Opin Neurobiol. 2004;14(2):186-191. doi:10.1016/j.conb.2004.03.001
30. Uğuz AC, Nazıroğlu M. Effects of selenium on calcium signaling and apoptosis in rat dorsal root ganglion neurons induced by oxidative stress. Neurochem Res. 2012;37(8):1631-1638. doi:10.1007/s11064-012-0758-5
31. Ghorbani A, Omidvar B, Parsi A. Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial. J Nephropathol. 2013;2(2):129-134. doi:10.12860/JNP.2013.21
32. Abdollahzadeh M, Panahpour H, Ghaheri S, Saadati H. Calcitriol supplementation attenuates cisplatin-induced behavioral and cognitive impairments through up-regulation of BDNF in male rats. Brain Res Bull. 2022;181:21-29. doi:10.1016/j.brainresbull.2022.01.006
33. Abdelkader NF, Saad MA, Abdelsalam RM. Neuroprotective effect of nebivolol against cisplatin‐associated depressive‐like behavior in rats. J Neurochem. 2017;141(3):449-460. doi:10.1111/jnc.13978
34. Yang J, Li H, Hao Z, et al. Mitigation Effects of selenium nanoparticles on depression-like behavior ınduced by fluoride in mice via the JAK2-STAT3 pathway. ACS Appl Mater Interfaces. 2022;14(3):3685-3700. doi:10.1021/acsami.1c18417
35. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 2005;15(4):316-328. doi:10.1016/j.numecd.2005.05.003
36. Ahiskali I, Ferah Okkay I, Mammadov R, et al. Effect of taxifolin on cisplatin-associated oxidative optic nerve damage in rats. Cutan Ocul Toxicol. 2021;40(1):1-6. doi:10.1080/15569527.2020.1844726
37. Gökpınar Ş, Koray T, Akçiçek E, Göksan T, Durmaz Y. Algal Antioksidanlar. Ege Üniversitesi Su Ürünleri Dergisi 2006;23(1):85-89.
38. Chen Y, Jungsuwadee P, Vore M, Butterfield DA, St Clair DK. Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interv. 2007;7(3):147-156. doi:10.1124/mi.7.3.6
39. Mert H, Kerem Ö, Mıs L, Yıldırım S, Mert N. Effects of protocatechuic acid against cisplatin-induced neurotoxicity in rat brains: an experimental study. Int J Neurosci. 2024;134(7):725-734. doi:10.1080/00207454.2022.2147430
40. Akomolafe SF, Asowata Ayodele AM. Roasted cashew (Anacardium occidentale L.) nut-enhanced diet forestalls cisplatin-initiated brain harm in rats. Heliyon. 2022;8(10):e11066. doi:10.1016/j.heliyon.2022.e11066
41. Romuk E, Szczurek W, Nowak P, et al. Effects of propofol on oxidative stress parameters in selected parts of the brain in a rat model of parkinson disease. Postepy Hig Med Dosw (Online). 2016;70(0):1441-1450. doi:10.5604/17322693.1227841
42. Cankara FN, Günaydın C, Çelik ZB, et al. Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity. Metab Brain Dis. 2021;36(2):339-349. doi:10.1007/s11011-020-00634-y
43. Kara O, Kilitci A. Antioxidant and apoptotic effect of edaravone on cisplatin-ınduced brain ınjury in rats. Acta Neurol Taiwan. 2024;33(1):7-13. doi:10.4103//ANT.33-1_111_0067
44. Bozkurt S, Arikan DC, Kurutas EB, et al. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg. 2012;47(9):1735-1741. doi:10.1016/j.jpedsurg.2012.03.053
45. Kornhauser C, Garcia Ramirez JR, Wrobel K, Pérez Luque EL, Garay Sevilla ME, Wrobel KJPCD. Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients. Prim Care Diabetes. 2008;2(2):81-85. doi:10.1016/j.pcd.2008.02.003