Yıl: 2023 Cilt: 30 Sayı: 2 Sayfa Aralığı: 175 - 182 Metin Dili: İngilizce DOI: 10.5455/annalsmedres.2022.09.287 İndeks Tarihi: 04-04-2023

Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings

Öz:
Aim: Due to the loss of neurons and neural network functions in the brain, cerebral ischemia is the leading cause of permanent disability in adults all over the world. An- tioxidants scavenge free radicals and protect tissues against oxidative damage caused by ischemia/reperfusion. This study aims to investigate the protective effects of myricetin, a powerful antioxidant, against cerebral ischemia/reperfusion injury. Materials and Methods: There were 5 experimental groups in this study; control, sham, ischemia/reperfusion (I/R), Myricetin 3 (Myr 3), and Myricetin 6 (Myr 6), and 8 rats in each group. Four-vessel occlusion was made to create ischemia. The ischemia and subsequent reperfusion period were 30 minutes each. One hour before ischemia, 3 mg/kg of myricetin was given to rats in the Myr 3 group and 6 mg/kg of myricetin was given to rats in the Myr 6 group. GolgiCox and Caspase3 stainings were carried, SOD, and MDA levels were investigated, and TNF-α mRNA expression levels were measured in brain tissue. Results: This study’s results showed that; the number of neurons decreased drastically in the CA1region of the hippocampus in the I/R group. Distance between cells increased, and the neurons were spaced apart and randomly distributed. Neuronal loss in the hip- pocampus was reduced and the amounts of neurons rise in the Myr 3 group compared to the I/R group. A significant decrease was detected in the SOD values of the I/R group. Compared to the I/R group, the SOD values of Myr 3 and Myr 6 groups increased sig- nificantly. MDA level of the I/R group increased significantly compared to the control. MDA values of Myr 3 and Myr 6 groups decreased significantly when compared to the I/R group. TNF-α mRNA expression level was significantly higher in the I/R group. A significant reduction was observed in the mRNA expression level in the Myr 3 group. Conclusion: In conclusion, the findings of this study suggest that myricetin is a promising agent for inhibiting the ischemia-induced cerebral inflammatory response and oxidative stress.
Anahtar Kelime: Cerebral ischemia Reperfusion Myricetin Protective effect

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. 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. doi:10.1159/000441106.
  • 2. Lefer AM, Lefer DJ. The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion. Cardiovasc Res. 1996;32(4):743–751. doi:10.1016/S0008- 6363(96)00073-9.
  • 3. Droge W. Free radicals in the physiological con- trol of cell function. Physiol Rev. 2002;82(1):47–95. doi:10.1152/physrev.00018.2001.
  • 4. Tang KS, Tan JS. The protective mechanisms of polydatin in cerebral ischemia. European J Pharmacol. 2019;842:133–138. doi:10.1016/j.ejphar.2018.10.039.
  • 5. McBean DE, Kelly PAT. Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion and four- vessel occlusion. General Pharmacology: The Vascular System. 1998;30(4),431-434. doi:10.1016/S0306-3623(97)00284-X.
  • 6. Groves TR, Wang J, Boerma M, Allen AR. Assessment of hip- pocampal dentric complexity in aged mice using the golgi-cox method. J Vis Exp. 2017;124:e55696. doi:10.3791/55696.
  • 7. Güleş Ö, Eren Ü. Methods for detection of apoptosis. Yüzüncü Yıl Üniversitesi Veteriner Fakültesi Dergisi. 2008;19(2):73-78.
  • 8. Roumen RMH, Hendriks T, Ven-Jongekrijg J, Nieuwenhuijzen GA, Sauerwein RW, van der Meer JW, et al. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respira- tory distress syndrome and multiple organ failure. Ann Surg. 1993;218(6):769-776. doi:10.1097/00000658-199312000-00011.
  • 9. White BC, Grossman LI, Krause GS. Brain injury by global ischemia and reperfusion: A theoretical perspective on mem- brane damage and repair. Neurology. 1993;43(9):1656. doi: 10.1212/WNL.43.9.1656.
  • 10. İşlekel H, İşlekel S, Guner G, Özdamar N. Evaluation of lipid peroxidation, cathepsin L and acid phosphatase activities in ex- perimental brain ischemia-reperfusion. Brain Res. 1999;843(1- 2):18-24. doi: 10.1016/S0006-8993(99)01845-4.
  • 11. Li RP, Wang ZZ, Sun MX, Hou XL, Sun Y, Deng ZF, et al. Polydatin protects learning and memory impairments in a rat model of vascular dementia. Phytomedicine. 2012;19(8-9):677- 681. doi: 10.1016/j.phymed.2012.03.002.
  • 12. Han T. Effects of salidroside pretreatment on expression of tu- mor necrosis factor-alpha and permeability of blood brain bar- rier in rat model of focal cerebral ischemia-reperfusion injury. Asian Pacific Journal of Tropical Medicine. 2013;6(2):156-158. doi: 10.1016/S1995-7645(13)60014-0.
  • 13. Ikeda K, Negishi H, Yamori Y. Antioxidant nutrients and hy- poxia/ischemia brain injury in rodents. Toxicology. 2003;189(1- 2):55–61. doi:10.1016/S0300-483X(03)00152-5.
  • 14. Taheri Y, Suleria HAR, Martins N, Sytar O, Beyatli A, Yeskaliyeva B, et al. Myricetin bioactive effects: Moving from preclinical evidence to potential clinical applications. BMC Com- plement Med Ther. 2020;20:241. doi:10.1186/s12906-020-03033- z.
  • 15. Jendroska K, Poewe W, Daniel SE, Pluess J, Iwerssen-Schmidt H, Paulsen J, et al. Ischemic stress induces deposition of amy- loid beta immunoreactivity in human brain. Acta Neuropathol. 1995;90:461–466. doi:10.1007/BF00294806.
  • 16. Lee KW, Kang NJ, Rogozin EA, Kim HG, Cho YY, Bode AM, et al. Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1. Carcinogenesis. 2007;28(9): 1918– 1927. doi:10.1093/carcin/bgm110.
  • 17. Ozcan F, Ozmen A, Akkaya B, Aliciguzel Y, Aslan M. Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. Clin Exp Med. 2012;12:265–272. doi:10.1007/s10238- 011-0167-0.
  • 18. Lu J, Papp LV, Gang J, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A. Inhibition of mammalian thioredoxin re- ductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res. 2006;66(8) 4410-4418. doi:10.1158/0008-5472.CAN-05-3310.
  • 19. Haa TK, Jungb I, Kimb ME, Baec SK, Lee JS. Anti- cancer activity of myricetin against human papillary thy- roid cancer cells involves mitochondrial dysfunction–mediated apoptosis. Biomedicine and Pharmacotherapy. 2017;91:378–384. doi:10.1016/j.biopha.2017.04.100.
  • 20. Sun L, Xu P, Fu T, Huang X, Song J, Chen M, et al. Myricetin against ischemic cerebral injury in rat middle cere- bral artery occlusion model. Mol Med Rep. 2018;17:3274–3280. doi:10.3892/mmr.2017.821.
  • 21. Ye S, Ma J, Ye C, Wang X. Neuroprotective and anti- inflammatory effects of myricetin 3-glucoside in a rat model of cerebral ischemia. Trop J Pharm Res. 2020;19(8):1710. doi:10.4314/tjpr.v19i8.20.
  • 22. Wu S, Yue Y, Peng A, Zhang L, Xiang J, Cao X, et al. Myricetin ameliorates brain injury and neurological defi¬cits via Nrf2 acti- vation after experimental stroke in middle aged rats. Food Funct. 2016;7(6):2624 2634. doi:10.1039/C6FO00419A.
  • 23. Al-Husein LMA, Mahbuba W, Mohammed M, Ghafil FA, Khaleq MAA, Hadi NR, et al. Myricetin Ameliorates Brain Damage Induces by Cerebral Ischemia-Reperfusion Injury in Rats. Asian Journal of Pharmaceutics. 2020;14(1):36-42.
  • 24. Kulevanova S, Stefova M, Panovska TK, Stafilov T. HPLC iden- tification and determination of myricetin, quercetin, kaempferol and total flavonoids in herbal drugs, Macedonian Pharmaceuti- cal Bulletin. 2002;48(1,2):25-30.
  • 25. Doğan İ, Doğan N. Estimation of sample size with resource equa- tion method in experimental animal studies, Türkiye Klinikleri J Biostat. 2020;12(2):211-217. doi:10.5336/biostatic.2020-73726.
  • 26. Oruc S, Gönül Y, Tunay K, Oruc OA, Bozkurt MF, Karavelioğlu E, et al. The antioxidant and antiapoptotic effects of crocin pre- treatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats. Life Sci, 2016;154:79-86. doi: 10.1016/j.lfs.2016.04.028.
  • 27. Koyu A, Gokcimen A, Ozguner F, Bayram DS, Kocak A. Eval- uation of the effects of cadmium on rat liver. Mol Cell Biochem. 2006;284:81–85, 2006. Doi:10.1007/s11010-005-9017-2.
  • 28. Guney T, Yıldız B, Altikat S, Kural N, Alatas O. Decreased antioxidant capacity and increased oxidative stress in patients with juvenile idiopathic arthritis. J Pediatric Sci. 2009;1:1-6. doi:10.17334/jps.05969.
  • 29. Dammak I, Boudaya S, Abdallah FB, Turki H, Attia H, Hen- tati B. Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo. International Journal of Dermatology. 2009;48(5):476-480. doi:10.1111/j.1365- 4632.2009.03998.x.
  • 30. Crosti N, Servidei T, Bajer J, Serra A. Modification of 6- hydroxydopamine technique for the correct determination of su- peroxide dismutase. J Clin Chem Clin Biochem. 1987;25:265- 266.
  • 31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265.
  • 32. Qiu Y, Cong N, Liang M, Wang Y, Wang J. Systems pharmacol- ogy dissection of the protective effect of myricetin against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart. Cardiovasc Toxicol. 2017;17:277–286. doi:10.1007/s12012- 016-9382-y.
  • 33. Yavtushenko IV, Nazarenko SM, Katrushov OV, Kostenko VO. Quercetin limits the progression of oxidative and nitrosative stress in the rats’ tissues after experimental traumatic brain injury. Wiad Lek. 2020;73(10):2127-2132. doi:10.36740/WLek202010104.
  • 34. Pekkarinen SS, Heinonen IM, Hopia AI. Flavonoids quercetin, myricetin, kaemferol and (+)-catechin as antioxidants in methyl linoleate. J Sci Food Agr. 1999;79(4):499-506. doi:10.1002/(SICI)1097-0010(19990315)79:4<499::AID- JSFA204>3.0.CO;2-U.
  • 35. Barzegar A. Antioxidant activity of polyphenolic myricetin in vitro cell-free and cell-based systems. Mol Biol Res Commun. 2016;5(2):87–95. PMID: 28097162.
  • 36. Pluta R, Ułamek-Kozioł M, Januszewski S, Czuczwar SJ. Participation of amyloid and tau protein in neuronal death and neurodegeneration after brain ischemia. Int J Mol Sci. 2020;21(13):4599. doi:10.3390/ijms21134599.
  • 37. Lu Q, Tucker D, Dong Y, Zhao N, Zhang Q. Neuroprotec- tive and functional improvement effects of methylene blue in global cerebral ischemia. Mol Neurobiol. 2016;53(8):5344–5355. doi:10.1007/s12035-015-9455-0.
  • 38. Janyou A, Wicha P, Jittiwat J, Suksamrarn A, Tocharus C, Tocharus J. Dihydrocapsaicin attenuates blood brain barrier and cerebral damage in focal cerebral ischemia/ reperfusion via oxidative stress and inflammatory. Sci Rep. 2017:10556. doi:10.1038/s41598-017-11181-5.
  • 39. Lambertsen KL, Biber K, Finsen B. Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab. 2012;32:1677-1698. doi:10.1038/jcbfm.2012.88.
  • 40. Pradillo JM, Denes A, Greenhalgh AD, Boutin H, Drake C, McColl BW, Barton E, Proctor SD, Russell JC, Rothwell NJ, Allan SM. Delayed administration of interleukin-1 receptor an- tagonist reduces ischemic brain damage and inflammation in comorbid rats. J Cereb Blood Flow Metab. 2012;32:1810-1819. doi:10.1038/jcbfm.2012.101.
  • 41. Shah ZA, Gilani RA, Sharma P, Vohora SB. Cerebroprotec- tive effect of Korean ginseng tea against global and focal mod- els of ischemia in rats. J Ethnopharmacol. 2005;101:299-307. doi:10.1016/j.jep.2005.05.002.
  • 42. Chandrashekhar VM, Ranpariya VL, Ganapaty S, Parashar A, Muchandi AA. Neuroprotective activity of Matricaria recutita linn against global model of ischemia in rats. J Ethnopharmacol. 2010;127(3):645-651. doi:10.1016/j.jep.2009.12.009.
  • 43. Sun Y, Lian M, Lin Y, Xu B, Li Y, Wen J, et al. Role of p-MKK7 in myricetin-induced protection against intestinal is- chemia/reperfusion injury. Pharmacol Res. 2018;129:432-442. doi:10.1016/j.phrs.2017.11.011.
  • 44. Ramezani M, Darbandi N, Khodagholi F, Hashemi A. Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer’s dis- ease. Neural Regen Res. 2016;11:1976–1980. doi: 10.4103/1673- 5374.197141.
  • 45. Yao Y, Lin G, Xie Y, Ma P, Li G, Meng Q, Wu T. Preformula- tion studies of myricetin: A natural antioxidant flavonoid. Die Pharm. 2014;69:19–26. doi:10.1691/ph.2014.3076.
  • 46. Jiang J, Yuan X, Wang T, Chen H, Zhao H, Yan X, et al. Antioxidative and cardioprotective effects of to- tal flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart. Cardiovasc Toxicol. 2014;14(1).74–82. doi:10.1007/s12012-013-9221-3.
  • 47. Abd-Elsameea AA, Moustaf AA, Mohamed AM. Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/ reperfusion. Eur Rev Med Pharmacol Sci. 2014;18(16):2387–2392.
  • 48. Mertoğlu C, Senel U, Cayli S, Tas U, Küskü Kiraz Z, Özyurt H. Protective role of methylprednisolone and heparin in ischaemic- reperfusion injury of the rat testicle. Andrologia. 2016;48(7):737- 744. doi:10.1111/and.12503.
  • 49. Öztürk D, Tanyeli A, Erdoğan DG, Güler MC, Eraslan E, Baylan H. The effects of myricetin against testicular and lung injury induced by testicular ischemia reperfusion model. Sakarya Med J. 2021;11(1):109-114. doi:10.31832/smj.783480.
  • 50. Chen YF, Wang YW, Huang WS, Lee MM, Wood WG, Le- ung YM Tsai HY. Trans Cinnamaldehyde, An essential oil in cinnamon powder, ameliorates cerebral ischemia induced brain injury via inhibition of neuroinflammation through attenu¬ation of iNOS, COX 2 expression and NFκ B signaling pathway. Neu- romol Med. 2016;18:322 333. doi:10.1007/s12017-016-8395-9.
  • 51. Jang JH, Lee SH, Jung K, Yoo H, Park G. Inhibitory effects of myricetin on lipopolysaccharide-induced neuroinflammation. Brain Sci. 2020;10(1):32. doi:10.3390/brainsci10010032.
  • 52. Liang LJ, Yang JM and Jin XC. Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke. Med Gas Res. 2016;6(1):33 38. doi:10.4103/2045-9912.179343.
  • 53. Jing N, Li X. Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway. Open Med. (Wars). 2019;14:719– 725. doi:10.1515/med-2019-0083.
APA Çeliközlü S, Köktürk S, Özyiğit F, altıkat s, Çeliközlü H (2023). Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. , 175 - 182. 10.5455/annalsmedres.2022.09.287
Chicago Çeliközlü Saadet,Köktürk Sibel,Özyiğit Filiz,altıkat said,Çeliközlü Halit Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. (2023): 175 - 182. 10.5455/annalsmedres.2022.09.287
MLA Çeliközlü Saadet,Köktürk Sibel,Özyiğit Filiz,altıkat said,Çeliközlü Halit Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. , 2023, ss.175 - 182. 10.5455/annalsmedres.2022.09.287
AMA Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. . 2023; 175 - 182. 10.5455/annalsmedres.2022.09.287
Vancouver Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. . 2023; 175 - 182. 10.5455/annalsmedres.2022.09.287
IEEE Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H "Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings." , ss.175 - 182, 2023. 10.5455/annalsmedres.2022.09.287
ISNAD Çeliközlü, Saadet vd. "Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings". (2023), 175-182. https://doi.org/10.5455/annalsmedres.2022.09.287
APA Çeliközlü S, Köktürk S, Özyiğit F, altıkat s, Çeliközlü H (2023). Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. Annals of Medical Research, 30(2), 175 - 182. 10.5455/annalsmedres.2022.09.287
Chicago Çeliközlü Saadet,Köktürk Sibel,Özyiğit Filiz,altıkat said,Çeliközlü Halit Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. Annals of Medical Research 30, no.2 (2023): 175 - 182. 10.5455/annalsmedres.2022.09.287
MLA Çeliközlü Saadet,Köktürk Sibel,Özyiğit Filiz,altıkat said,Çeliközlü Halit Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. Annals of Medical Research, vol.30, no.2, 2023, ss.175 - 182. 10.5455/annalsmedres.2022.09.287
AMA Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. Annals of Medical Research. 2023; 30(2): 175 - 182. 10.5455/annalsmedres.2022.09.287
Vancouver Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings. Annals of Medical Research. 2023; 30(2): 175 - 182. 10.5455/annalsmedres.2022.09.287
IEEE Çeliközlü S,Köktürk S,Özyiğit F,altıkat s,Çeliközlü H "Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings." Annals of Medical Research, 30, ss.175 - 182, 2023. 10.5455/annalsmedres.2022.09.287
ISNAD Çeliközlü, Saadet vd. "Myricetin ameliorates cerebral ischemia/reperfusion damage in rat four vessel occlusion model: Histological, biochemical, molecular findings". Annals of Medical Research 30/2 (2023), 175-182. https://doi.org/10.5455/annalsmedres.2022.09.287