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Serebral İskemi/Reperfüzyon Hasarında Hesperidinin Nöroprotektif Etkisi

Year 2023, Volume: 13 Issue: 2, 265 - 276, 30.06.2023
https://doi.org/10.31832/smj.1182213

Abstract

Amaç: Bu çalışmanın amacı, sıçanlarda serebral iskemi/reperfüzyon hasarına karşı hesperidinin farklı dozlarının koruyucu etkisini araştırmaktır.
Gereç ve Yöntemler: Çalışmada kontrol, sham, iskemi/reperfüzyon (İ/R), hesperidin 50 (Hes 50) ve hesperidin 100 (Hes 100) olmak üzere 5 grup hazırlandı. İskemi oluşturmak için Pulsinelli ve Brierly'nin dört damar oklüzyon modeli kullanıldı. 30 dakika iskemi ve 30 dakika reperfüzyon uygulandı. Hesperidin, iskemiden 30 dakika önce intraperitonal olarak enjekte edildi. Histopatolojik çalışma için beyin dokusuna Golgi Cox ve Caspase 3 boyaması uygulandı. Ayrıca beyin dokusunda SOD, CAT, MDA ve total protein seviyeleri belirlendi ve TNF-α mRNA ekspresyon seviyeleri RT-qPCR tekniği ile ölçüldü.
Bulgular: İ/R grubunda kontrol grubuna göre CAT ve SOD değerlerinde azalma, MDA değerinde artış, toplam protein değerinde hafif artış saptandı. Hes 50 ve Hes 100 gruplarında, İ/R grubu ile kıyaslandığında CAT, SOD değerleri arttı, MDA ve toplam protein değerleri önemli ölçüde azaldı. I/R grubunda kontrol grubuna kıyasla önemli bir CA1 nöron kaybı gözlendi. Hes 50 grubunda I/R grubuna göre hipokampustaki nöron hasarının azaldığı ve nöron sayısının istatistiksel olarak anlamlı düzeyde arttığı bulundu. Beyin dokusundaki TNF-α mRNA ekspresyon değerleri, I/R grubunda kontrol ve sham gruplarına göre anlamlı derecede yüksekti. Hes 50 grubunda I/R grubuna kıyasla mRNA ekspresyon miktarında önemli bir azalma gözlendi.
Sonuç: Bu çalışmanın sonuçlarına göre, antioksidan potansiyeli olan hesperidin, serebral iskemi/reperfüzyonunun neden olduğu oksidatif stres hasarına karşı nöroprotektif ve antiinflamatuar etkiler göstermiştir. Düşük doz hesperidin (Hes 50) grubunda antiinflamatuar ve nöroprotektif etkiler öne çıkarken, hem Hes 50 hem de Hes 100 gruplarında antioksidan etkinin daha baskın olduğu tespit edilmiştir.

Supporting Institution

Kütahya Dumlupınar Üniversitesi BAP Birimi

Project Number

2018-07

References

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  • 3. Noshy PA, Azouz RA. Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats. Neurotoxicology and Teratology 2021; 86:106981. doi:10.1016/j.ntt.2021.106981
  • 4. Kara S, Gencer B, Karaca T, Tufan HA, Arikan S, Ersan I, Karaboga I, Hanci,V, Protective effect of hesperidin and naringenin against apoptosis in ischemia/reperfusion-induced retinal injury in rats. Sci. World J. 2014;30: 797–824. doi:10.1155/2014/797824.
  • 5. Bayomy NA, Elshafhey SH, ElBakary RH, Abdelaziz EZ. Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: histological, immunohistochemical and biochemical study. Tissue Cell. 2014; 46(5):304-10. doi:10.1016/j.tice.2014.05.009
  • 6. Xie Q, Gao S, Lei M, Li Z. Hesperidin suppresses ERS-induced inflammation in the pathogenesis of non-alcoholic fatty liver disease. Aging (Albany NY) 2022; 14(3):1265. doi:10.18632/aging.203817
  • 7. Selvaraj P, Pugalendi KV. Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats. Redox Report 2010; 15(5):217-223. doi:10.1179/135100010X12826446921509.
  • 8. Su D, Li P, Wang X, Zhang W, Zhang Y, Wu C, Zhang W et al. Observing malondialdehyde-mediated signaling pathway in cerebral ischemia reperfusion injury with a specific nanolight. Analytical chemistry 2020;92(3): 2748-2755. doi:10.1021/acs.analchem.9b05008
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  • 13. Wang W, Liu X, Lu H, Liu L, Wang Y, Yu Y, Zhang T. A method for predicting the success of Pulsinell’s four-vessel occlusion rat model by LDF monitoring of cerebral blood flow decline. Journal of Neuroscience Methods 2019; 328:108439. doi:10.1016/j.jneumeth.2019.108439
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  • 20. Oztanir MN, Ciftci O, Cetin A, Aladag MA. Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci. 2014; 35(9):1393-1399. doi:10.1007/s10072-014-1725-5
  • 21. Raza SS, Khan MM, Ahmad A, Ashafaq M, Khuwaja G, Tabassum R, Javed H, Siddiqui MS, Safhi MM, Islam F. Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 2011; 28(1420):93-105. doi:10.1016/j.brainres.2011.08.047
  • 22. Putteeraj M, Lim WL, Teoh SL, Yahaya MF. Flavonoids and its neuroprotective effects on brain ischemia and neurodegenerative diseases. Current drug targets 2018; 19(14):1710-1720. doi:10.2174/1389450119666180326125252
  • 23. Dimpfel W. Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in vitro. J. Pharm. Pharmacol 2006; 58:375–379. doi:10.1211/jpp.58.3.0012
  • 24. Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C.Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem 2003; 85(1):180–192. doi:10.1046/j.1471-4159.2003.01652.x.PMID12641740
  • 25. Li X, Hu X, Wang J, Xu W, Yi C, Ma R, Jiang H. Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. Int J Mol Med 2018; 42:1917e24. doi:10.3892/ijmm.2018.3794
  • 26. Celik E, Oguzturk H, Sahin N, Turtay MG, Oguz F, Ciftci O. Protective effects of hesperidin in experimental testicular ischemia/reperfusion injury in rats Arch Med Sci 2016;12(5):928–934 doi:https://doi.org/10.5114/aoms.2015.47697
  • 27. Chen M, Gu H, Ye Y, Lin B, Sun L, Deng W, Zhang J, Liu J. Protectiveeffects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes, Food Chem. Toxicol 2010; 48:2980–2987. doi:10.1016/j.fct. 2010.07.037.
  • 28. Gaur V, Kumar A. Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction. Pharmacol Rep 2010; 62:635–648.
  • 29. Park HK, Kang SW, Park MS. Hesperidin Ameliorates Hepatic Ischemia-Reperfusion Injury in Sprague-Dawley Rats. Transplant Proc. 2019; 51(8):2828-2832. doi:10.1016/j.transproceed.2019.02.059
  • 30. Park WS, Park MS, Kang SW, Jin SA, Jeon Y, Hwang J, Kim SK. Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats). Transplant Proc. 2019; 51(8):2838-2841. doi:10.1016/j.transproceed.2019.02.055.
  • 31. El-Sayed SM, Abo-Salem OM, Abd-Ellah MF, Abd-Alla GM. Hesperidin, an antioxidant flavonoid, prevents acrylonitrile-induced oxidative stress in rat brain. J. Biochem. Mol. Toxicol 2008; 22:268–273. doi:10.1002/jbt.20237
  • 32. Gaur V, Aggarwal A, Kumar A. Possible nitric oxide mechanism in the protective effect of hesperidin against ischemic reperfusion cerebral injury in rats. Indian J Exp Biol. 2011; 49(8):609-618.
  • 33. Kumar P, Kumar A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats, Possible role of nitric oxide. Behav. Brain Res 2010; 206(1):38–46. doi:0.1016/j.bbr.2009.08.028
  • 34. Kumar BH, Kumar BD, Diwan PV. Hesperidin, a citrus flavonoid, protects against L-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats. Pharmaceutical Biology 2017; 55(1):146–155. doi:10.1080/13880209.2016.1231695
  • 35. Tsai YF, Chen YR, Chen JP, Tang Y, Yang KC. Effect of hesperidin on anti-inflammation and cellular antioxidant capacity in hydrogen peroxide-stimulated human articular chondrocytes. Process Biochemistry 2019; 85:175–184. doi:10.1016/j.procbio.2019.07.014
  • 36. Kumar M, Dahiya V, Kasala ER, Bodduluru LN, Lahkar M. The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence. Biomed Pharmacother. 2017;89 :1207-1215. doi:10.1016/j.biopha.2017.03.008.
  • 37. Sahu BD, Kuncha M, Sindhura GJ, Sistla R. Hesperidin attenuate scisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 2013; 20:453–460. doi:10.1016/j.phymed.2012.12.001.
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  • 39. Kumar PP, Kumar KTS, Nainita MK, Tarun AS, Ramudu BGR, Deepika K, Pramoda A, Yasmeen C. Cerebroprotective Potential of Hesperidin Nanoparticles Against Bilateral Common Carotid Artery Occlusion Reperfusion Injury in Rats and In silico Approaches. Neurotox Res 2020; 37(2):264-274. doi:10.1007/s12640-019-00098-8.
  • 40. Meng C, Guo Z, Li D, Li H, He J, Wen D, Luo B. Preventive effect of hesperidin modulates inflammatory responses and antioxidant status following acute myocardial infarction through the expression of PPAR γ and Bcl 2 in model mice. Mol Med Rep. 2018; 17(1):1261-1268. doi:10.3892/mmr.2017.7981
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Neuroprotective Effects of Hesperidin In Cerebral Ischemia/Reperfusion Injury

Year 2023, Volume: 13 Issue: 2, 265 - 276, 30.06.2023
https://doi.org/10.31832/smj.1182213

Abstract

Aim: The aim of this study was to investigate the protective effect of different doses of hesperidin against cerebral ischemia/reperfusion injury.
Material and Method: In this study, 5 groups were prepared as control, sham, ischemia/reperfusion (I/R), hesperidin50 (Hes 50), and hesperidin100 (Hes 100). Four vessel occlusion model was used to induce ischemia. 30minutes of ischemia and 30minutes of reperfusion were applied. Hesperidin was injected intraperitoneally 30minutes before ischemia. GolgiCox and Caspase3 staining were performed, SOD, CAT, MDA, and total protein levels were determined, TNF-α mRNA expression levels were measured in brain tissue.
Results: In the I/R group, CAT and SOD values decreased, the MDA value increased, a slight increase in the total protein value was found compared to the control group. CAT, SOD values increased, MDA and total protein values decreased significantly in Hes 50 and Hes 100 groups. A significant loss of CA1 neurons was observed in the I/R group. It was found that neuron damage in the hippocampus decreased and the number of neurons increased statistically significantly in the Hes 50 group compared to the I/R group. TNF-α mRNA expression values in brain tissue were significantly higher in the I/R group than control and sham groups. A significant decrease in the amount of mRNA expression was observed in the Hes50 group compared to the I/R group.
Conclusion: According to the results of this study, hesperidin, which has antioxidant potential, showed neuroprotective and anti-inflammatory effects against oxidative stress damage caused by cerebral ischemia/reperfusion. While anti-inflammatory and neuroprotective effects were prominent in the low-dose hesperidin (Hes 50) group, the antioxidant effect was more dominant in both Hes 50 and Hes 100 groups.

Project Number

2018-07

References

  • 1. Süleyman H, Özçiçek A. Molecular Mechanism of Ischemia Reperfusion Injury. Arch Basic Clin Res 2020; 2(1):25-7.
  • 2. Feigin VL, Mensah GA, Norrving B, Murray CJ, Roth GA. Group, G. B. D. S. P. E. Atlas of the Global Burden of Stroke (1990–2013): The GBD 2013 Study. Neuroepidemiology 2015; 45(3):230–236.
  • 3. Noshy PA, Azouz RA. Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats. Neurotoxicology and Teratology 2021; 86:106981. doi:10.1016/j.ntt.2021.106981
  • 4. Kara S, Gencer B, Karaca T, Tufan HA, Arikan S, Ersan I, Karaboga I, Hanci,V, Protective effect of hesperidin and naringenin against apoptosis in ischemia/reperfusion-induced retinal injury in rats. Sci. World J. 2014;30: 797–824. doi:10.1155/2014/797824.
  • 5. Bayomy NA, Elshafhey SH, ElBakary RH, Abdelaziz EZ. Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: histological, immunohistochemical and biochemical study. Tissue Cell. 2014; 46(5):304-10. doi:10.1016/j.tice.2014.05.009
  • 6. Xie Q, Gao S, Lei M, Li Z. Hesperidin suppresses ERS-induced inflammation in the pathogenesis of non-alcoholic fatty liver disease. Aging (Albany NY) 2022; 14(3):1265. doi:10.18632/aging.203817
  • 7. Selvaraj P, Pugalendi KV. Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats. Redox Report 2010; 15(5):217-223. doi:10.1179/135100010X12826446921509.
  • 8. Su D, Li P, Wang X, Zhang W, Zhang Y, Wu C, Zhang W et al. Observing malondialdehyde-mediated signaling pathway in cerebral ischemia reperfusion injury with a specific nanolight. Analytical chemistry 2020;92(3): 2748-2755. doi:10.1021/acs.analchem.9b05008
  • 9. Tu Q, Wang R, Ding B, Zhong W, Cao H. Protective and antioxidant effect of Danshen polysaccharides on cerebral ischemia/reperfusion injury in rats. International Journal of Biological Macromolecules, 2013; 60:268-271. doi:10.1016/j.ijbiomac.2013.05.035
  • 10. Roumen RMH, Hendriks T, Ven-Jongekrijg J, Nieuwenhuijzen GAP, Sauerwein R, van der Meer JWM, Goris RJA. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Annals of Surgery 1993; 218(6):769-776. doi:10.1097/00000658-199312000-00011
  • 11. Zhang WF, Jin YC, Li XM, Yang Z, Wang D, Cui JJ. Protective effects of leptin against cerebral ischemia/reperfusion injury. Experimental and Therapeutic Medicine 2019; 17(5):3282-3290. doi:10.3892/etm.2019.7377
  • 12. Gungor ANC, Gencer M, Karaca T, Hacivelioglu S, Uysal A, Korkmaz F, Demirtas S, Cosar E. The effect of hesperetin on ischemia-reperfusion injury in rat ovary. Arch Gynecol Obstet 2014; 290(4):763-769. doi:10.1007/s00404-014-3267-8
  • 13. Wang W, Liu X, Lu H, Liu L, Wang Y, Yu Y, Zhang T. A method for predicting the success of Pulsinell’s four-vessel occlusion rat model by LDF monitoring of cerebral blood flow decline. Journal of Neuroscience Methods 2019; 328:108439. doi:10.1016/j.jneumeth.2019.108439
  • 14. Hadwan MH, Abed HN. Data supporting the spectrophotometric method for the estimation of catalase activity. Data in Brief 2016; 6:194-199. doi:10.1016/j.dib.2015.12.012
  • 15. Coban A, Ciftci M, Ozdemir H, Altikat,S. Purification and characterization of catalase enzymes from chicken liver and sheep erythrocytes. Asian J Chem 2007; 19(5):3941-3953.
  • 16. Chafik A, Essamadi A, Çelik SY, Mavi A. Purification and biochemical characterization of a novel copper, zinc superoxide dismutase from liver of camel (Camelus dromedarius): An antioxidant enzyme with unique properties. Bioorganic Chemistry 2019; 86:428-436. doi:10.1016/j.bioorg.2019.02.024
  • 17. Ürek RÖ, Tarhan L. Purification and characterization of superoxide dismutase from chicken liver. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2001; 128(2):205-212. doi:10.1016/S1096-4959(00)00300-6
  • 18. Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1990; 186:421-431. doi:10.1016/0076-6879(90)86135-I
  • 19. Waterborg, JH. The Lowry method for protein quantitation. In The protein protocols handbook. Humana Press, Totowa, NJ. 2009; pp. 7-10.
  • 20. Oztanir MN, Ciftci O, Cetin A, Aladag MA. Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci. 2014; 35(9):1393-1399. doi:10.1007/s10072-014-1725-5
  • 21. Raza SS, Khan MM, Ahmad A, Ashafaq M, Khuwaja G, Tabassum R, Javed H, Siddiqui MS, Safhi MM, Islam F. Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 2011; 28(1420):93-105. doi:10.1016/j.brainres.2011.08.047
  • 22. Putteeraj M, Lim WL, Teoh SL, Yahaya MF. Flavonoids and its neuroprotective effects on brain ischemia and neurodegenerative diseases. Current drug targets 2018; 19(14):1710-1720. doi:10.2174/1389450119666180326125252
  • 23. Dimpfel W. Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in vitro. J. Pharm. Pharmacol 2006; 58:375–379. doi:10.1211/jpp.58.3.0012
  • 24. Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C.Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem 2003; 85(1):180–192. doi:10.1046/j.1471-4159.2003.01652.x.PMID12641740
  • 25. Li X, Hu X, Wang J, Xu W, Yi C, Ma R, Jiang H. Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. Int J Mol Med 2018; 42:1917e24. doi:10.3892/ijmm.2018.3794
  • 26. Celik E, Oguzturk H, Sahin N, Turtay MG, Oguz F, Ciftci O. Protective effects of hesperidin in experimental testicular ischemia/reperfusion injury in rats Arch Med Sci 2016;12(5):928–934 doi:https://doi.org/10.5114/aoms.2015.47697
  • 27. Chen M, Gu H, Ye Y, Lin B, Sun L, Deng W, Zhang J, Liu J. Protectiveeffects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes, Food Chem. Toxicol 2010; 48:2980–2987. doi:10.1016/j.fct. 2010.07.037.
  • 28. Gaur V, Kumar A. Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction. Pharmacol Rep 2010; 62:635–648.
  • 29. Park HK, Kang SW, Park MS. Hesperidin Ameliorates Hepatic Ischemia-Reperfusion Injury in Sprague-Dawley Rats. Transplant Proc. 2019; 51(8):2828-2832. doi:10.1016/j.transproceed.2019.02.059
  • 30. Park WS, Park MS, Kang SW, Jin SA, Jeon Y, Hwang J, Kim SK. Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats). Transplant Proc. 2019; 51(8):2838-2841. doi:10.1016/j.transproceed.2019.02.055.
  • 31. El-Sayed SM, Abo-Salem OM, Abd-Ellah MF, Abd-Alla GM. Hesperidin, an antioxidant flavonoid, prevents acrylonitrile-induced oxidative stress in rat brain. J. Biochem. Mol. Toxicol 2008; 22:268–273. doi:10.1002/jbt.20237
  • 32. Gaur V, Aggarwal A, Kumar A. Possible nitric oxide mechanism in the protective effect of hesperidin against ischemic reperfusion cerebral injury in rats. Indian J Exp Biol. 2011; 49(8):609-618.
  • 33. Kumar P, Kumar A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats, Possible role of nitric oxide. Behav. Brain Res 2010; 206(1):38–46. doi:0.1016/j.bbr.2009.08.028
  • 34. Kumar BH, Kumar BD, Diwan PV. Hesperidin, a citrus flavonoid, protects against L-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats. Pharmaceutical Biology 2017; 55(1):146–155. doi:10.1080/13880209.2016.1231695
  • 35. Tsai YF, Chen YR, Chen JP, Tang Y, Yang KC. Effect of hesperidin on anti-inflammation and cellular antioxidant capacity in hydrogen peroxide-stimulated human articular chondrocytes. Process Biochemistry 2019; 85:175–184. doi:10.1016/j.procbio.2019.07.014
  • 36. Kumar M, Dahiya V, Kasala ER, Bodduluru LN, Lahkar M. The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence. Biomed Pharmacother. 2017;89 :1207-1215. doi:10.1016/j.biopha.2017.03.008.
  • 37. Sahu BD, Kuncha M, Sindhura GJ, Sistla R. Hesperidin attenuate scisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 2013; 20:453–460. doi:10.1016/j.phymed.2012.12.001.
  • 38. Zhang Y, Zhang Y. lncRNA ZFAS1 improves neuronal injury and inhibits inflammation, oxidative stress, and apoptosis by sponging miR-582 and upregulating NOS3 expression in cerebral ischemia/reperfusion injury. Inflammation 2020;43(4):337-1350. doi:10.1007/s10753-020-01212-1
  • 39. Kumar PP, Kumar KTS, Nainita MK, Tarun AS, Ramudu BGR, Deepika K, Pramoda A, Yasmeen C. Cerebroprotective Potential of Hesperidin Nanoparticles Against Bilateral Common Carotid Artery Occlusion Reperfusion Injury in Rats and In silico Approaches. Neurotox Res 2020; 37(2):264-274. doi:10.1007/s12640-019-00098-8.
  • 40. Meng C, Guo Z, Li D, Li H, He J, Wen D, Luo B. Preventive effect of hesperidin modulates inflammatory responses and antioxidant status following acute myocardial infarction through the expression of PPAR γ and Bcl 2 in model mice. Mol Med Rep. 2018; 17(1):1261-1268. doi:10.3892/mmr.2017.7981
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There are 46 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Saadet Çeliközlü 0000-0001-9825-6458

Filiz Özyiğit 0000-0002-0062-4281

Said Altıkat 0000-0002-5763-3787

Sibel Köktürk 0000-0001-5636-3300

Halit Çeliközlü 0000-0002-0456-7077

Project Number 2018-07
Early Pub Date June 27, 2023
Publication Date June 30, 2023
Submission Date September 30, 2022
Published in Issue Year 2023 Volume: 13 Issue: 2

Cite

AMA Çeliközlü S, Özyiğit F, Altıkat S, Köktürk S, Çeliközlü H. Serebral İskemi/Reperfüzyon Hasarında Hesperidinin Nöroprotektif Etkisi. Sakarya Tıp Dergisi. June 2023;13(2):265-276. doi:10.31832/smj.1182213

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