تاثیر سینئول بر روی پارامترهای رفتاری، بیوشیمیایی و هیستولوژیکی در موش‌های نر نژاد ویستار آلزایمری شده

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه زیست شناسی، واحد علوم و تحقیقات تهران، دانشگاه آزاد اسلامی، تهران، ایران

چکیده

بیماری آلزایمر یکی از بیماری­های تحلیل­برنده­ سیستم عصبی است که جمعیت بسیاری را در سراسر جهان درگیر کرده و تا کنون درمان قطعی برای آن یافت نشده است. هدف از تحقیق حاضر بررسی اثر سینئول به عنوان یک ماده­ی آنتی­اکسیدان طبیعی بر پارامترهای رفتاری، بیوشیمیایی و هیستولوژیکی در بیماری آلزایمر بود. برای این منظور تعداد 36 سر موش نر نژاد ویستار به طور تصادفی به 6 گروه تقسیم شدند. گروه کنترل بدون جراحی و تیمار خاص بودند. سایر گروه­ها تحت جراحی قرار گرفته و به چهار گروه بتا آمیلوئید و به یک گروه PBS (حلال بتا آمیلوئید) تزریق شد. گروه شم با تویین 80 (حلال سینئول) تیمار شد و دو گروه تیمار هم با دوز­های 02/0 و 04/0 میلی­گرم/کیلوگرم سینئول تیمار شدند. گروه کنترل، گروه آلزایمری و گروه PBS هیچ تیماری دریافت نکردند. در نهایت پارامترهای رفتاری (زمان رفتن موش­های به بخش تاریک دستگاه شاتل باکس)، بیوشیمیایی (مالون دی­آلدهید، سوپراکسید دیسموتاز، TNF-α) و بافتی (با رنگ­آمیزی هماتوکسیلین-ائوزین و تیوفلاوین S) مورد بررسی قرار گرفتند. در موش­های آلزایمری مدت زمانی که طول می­کشید تا موش به بخش تاریک شاتل باکس برود به طور معناداری (001/0 p <) کمتر از موش­های کنترل بود. سطح مالون دی­آلدهید و TNF-α نیز در موش­های آلزایمری نسبت به گروه کنترل افزایش معنادار و سطح سوپراکسید دیسموتاز کاهش معناداری داشت (001/0 p <). بررسی­های بافتی نیز نشان داد که در موش­های آلزایمری مرگ سلولی نورونی به طور گسترده در هیپوکامپ رخ داده و پلاک­های آمیلوئیدی نیز افزایش داشته­اند (001/0 p <). تیمار موش­ها با سینئول به صورت وابسته به دوز تمامی موارد ذکر شده را به طور معناداری بهبود بخشید. سینئول احتمالاً می­تواند به عنوان یک ماده­ی آنتی­اکسیدان طبیعی مناسب در جهت درمان بیماری آلزایمر و کاهش علائم آن مورد استفاده قرارگیرد که این امر نیازمند انجام تحقیقات بیشتر می­باشد.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of Cineole on Biochemical, Behavioral and Histological Parameters in Alzheimer’s Male Wistar Rat Model

نویسندگان [English]

  • Elnaz Khameneh
  • Parichehreh Yaghmaei
  • Maryam Ghobeh
Department of Biology, Islamic Azad University, Science and Research Branch, Tehran, Iran
چکیده [English]

The Alzheimer’s disease is one of the neurodegenerative diseases affecting many individuals around the world with no definitive cure. The aim of this study was to investigate the effect of cineole, as a natural antioxidant, on the behavioral, biochemical, and histological symptoms of Alzheimer’s disease in Wistar rats. Thirty-six male Wistar rats were randomly assigned to six groups. The control group underwent any surgery with no special treatment. The other groups underwent surgery and were assigned to four beta-amyloid groups: one group receiving PBS (beta-amyloid solvent); the sham group was treated with tween 80 (cineole solvent) and the two experimental groups were treated with cineole at 0.02 and 0.04 mg/kg doses. The control group, the Alzheimer’s group and the PBS group did not receive any treatments. Finally, behavioral (Shuttle box), biochemical (malondialdehyde (MDA), superoxide dismutase, TNF-α) and histological parameters (H&E and Thioflavine S staining) were investigated. In Alzheimer’s-induced rats, the time it took for the rats to go to the dark part of the shuttle box was significantly (p < 0.001) shorter than that of the control group. The levels of malondialdehyde and TNF-α in these rats were significantly increased and the level of superoxide dismutase was significantly decreased compared to the control group (p < 0.001). Furthermore, histological studies showed that in Alzheimer’s-induced rats, neuronal cell death occurred extensively in the hippocampus and amyloid plaques increased. Treatment of rats with cineole improved all of the investigated parameters significantly in a dose-dependent manner. Cineole may be used as a suitable natural antioxidant to treat Alzheimer’s disease and reduce its symptoms, requiring further research.
 
.

کلیدواژه‌ها [English]

  • Alzheimer’s disease
  • Cineole
  • SOD
  • MDA
  • Neurogenesis
  • Amyloid Plaques
  1. Alzheimer's Association Report, 2018. Alzheimer's disease facts and figures. Alzheimer's and Dementia, 14(3): 367-429.
  2. Baek S., Kim S.H., 2016. Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats. Journal of Exercise Rehabilitation, 12(6): 526.
  3. Bhowal M., Gopal M., 2015. Eucalyptol: Safety and pharmacological profile. Journal of Pharmaceutic Science, 5: 125-131.
  4. Birben E., Sahiner U.M., Sackesen C., Erzurum S., Kalayci O., 2012. Oxidative stress and antioxidant defense. World Allergy Organization Journal, 5(1): 1.
  5. Butterfield D.A., Halliwell B., 2019. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nature Reviews Neuroscience, 20(3): 148-160.
  6. Cao K., Dong Y.T., Xiang J., Xu Y., Hong W., Song H., Guan, Z.Z., 2018. Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in various regions of the brains of patients with Alzheimer's disease. Journal of Clinical Pathology, 71(12): 1090-1099.
  7. Ciftci O., Ozdemir I., Tanyildizi S., Yildiz S., Oguzturk, H., 2011. Antioxidative effects of curcumin, β-myrcene and 1, 8-cineole against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver. Toxicology and industrial health, 27(5): 447-453.
  8. Cummings J., Lee G., Ritter A., Zhong, K., 2018. Alzheimer's disease drug development pipeline: 2018. Alzheimer's and Dementia. Translational Research and Clinical Interventions, 4: 195-214.
  9. Cunningham C., Campion S., Lunnon K., Murray C.L., Woods J.F., Deacon R.M., Rawlins J.N.P., Perry V.H., 2009. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biological Psychiatry, 65(4): 304-312.
  10. Farivar M., Hooshmandi Z., Setorki M., Amini S., 2020. Protective Effect of 1, 8-cineole on Learning and Memory Impairment Induced by Cerebral Hypoperfusion in Male Rats. Qom University of Medical Sciences Journal, 14(4): 40-47.
  11. Hoseini S.M., Rajabiesterabadi H., Khalili M., Yousefi M., Hoseinifar S.H., Van Doan H., 2020. Antioxidant and immune responses of common carp (Cyprinus carpio) anesthetized by cineole: Effects of anesthetic concentration. Aquaculture, 520: 734680.
  12. Huang J., Upadhyay U.M., Tamargo R.J., 2006. Inflammation in stroke and focal cerebral ischemia. Surgical Neurology, 66(3): 232-245.
  13. Huang W.J., Zhang X., Chen W.W., 2016. Role of oxidative stress in Alzheimer's disease. Biomedical Reports, 4(5): 519-522.
  14. Jimenez S., Baglietto-Vargas D., Caballero C., Moreno-Gonzalez I., Torres M., Sanchez-Varo R., Ruano D., Vizuete M., Gutierrez A., Vitorica J., 2008. Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: age-dependent switch in the microglial phenotype from alternative to classic. Journal of Neuroscience, 28(45): 11650-11661.
  15. Juergens L.J., Racké K., Tuleta I., Stoeber M., Juergens U.R., 2017. Anti-inflammatory effects of 1,8-cineole (eucalyptol) improve glucocorticoid effects in vitro: a novel approach of steroid-sparing add-on therapy for COPD and asthma? Synergy, 5: 1-8.
  16. Juergens L.J., Tuleta I., Stoeber M., Racké K., Juergens U.R., 2018. Regulation of monocyte redox balance by 1, 8-cineole (eucalyptol) controls oxidative stress and pro-inflammatory responses in vitro: A new option to increase the antioxidant effects of combined respiratory therapy with budesonide and formoterol? Synergy, 7: 1-9.
  17. Kryscio R.J., Abner E.L., Caban-Holt A., Lovell M., Goodman P., Darke A.K., Yee M., Crowley J., Schmitt F.A., 2017. Association of antioxidant supplement use and dementia in the prevention of Alzheimer’s disease by vitamin E and selenium trial (PREADViSE). JAMA Neurology, 74(5): 567-573.
  18. Lai Y.N., Li Y., Fu L.C., Zhao F., Liu N., Zhang F.X., Xu P.P., 2017. Combinations of 1, 8‐cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice. Journal of Medical Virology, 89(7): 1158-1167.
  19. Li Y., Lai Y., Wang Y., Liu N., Zhang F., Xu P., 2016. 1, 8-cineol protect against influenza-virus-induced pneumonia in mice. Inflammation, 39(4): 1582-1593.
  20. López-Riquelme N., Alom-Poveda J., Viciano-Morote N., Llinares-Ibor I., Tormo-Díaz, C., 2016. Apolipoprotein E ε4 allele and malondialdehyde level are independent risk factors for Alzheimer’s disease. SAGE Open Medicine, 4: 2050312115626731.
  21. Lori-Gooini Z., Rabiei Z., Farhadi B., Bijad E., Azomon E., Rafieian-Kopaei M., 2018. Investigation of chemical compounds and effects of Achilea wilhelmsii L essential oil on antioxidant and malondialdehyde levels of serum and brains of reserpined mice. Iranian Journal of Physiology and Pharmacology, 2(3): 176-166.
  22. Miguélez L., de Toda I.M., De la Fuente M., 2018. Oxidative stress in blood cells of men and women with Alzheimer's and Parkinson's diseases. Free Radical Biology and Medicine, 120: S98.
  23. Mirghaed A.T., Fayaz S., Hoseini S.M., 2019. Effects of dietary 1, 8-cineole supplementation on serum stress and antioxidant markers of common carp (Cyprinus carpio) acutely exposed to ambient ammonia. Aquaculture, 509: 8-15.
  24. Mohammadzadeh E., Alipour F., Khallaghi B., 2014. Evaluation of spatial memory impairment after intracerebroventricular streptozocin injection in adult rats. The Neuroscience Journal of Shefaye Khatam, 2(1): 40-45.
  25. Morales I., Cerda-Troncoso C., Andrade V., Maccioni R.B., 2017. The natural product curcumin as a potential coadjuvant in Alzheimer’s treatment. Journal of Alzheimer's Disease, 60(2): 451-460.
  26. Moss M., Oliver L., 2012. Plasma 1, 8-cineole correlates with cognitive performance following exposure to rosemary essential oil aroma. Therapeutic Advances in Psychopharmacology, 2(3): 103-113.
  27. Paul K., Ganguly U., Chakrabarti S., Bhattacharjee P., 2020. Is 1, 8-Cineole-Rich Extract of Small Cardamom Seeds More Effective in Preventing Alzheimer’s Disease than 1, 8-Cineole Alone? Neuromolecular Medicine, 22(1): 150-158.
  28. Pinto A., Bonucci A., Maggi E., Corsi M., Businaro R., 2018. Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease. Antioxidants, 7(5): 63.
  29. Proctor P., 2019. RE: SOD1 and SOD-mimetics as Alzheimer's Treatments. Clinical Pharmacology and Toxicology https://www.science.org/do/10.1126/comment.728226/full/
  30. Qian Z.J., Jung W.K., Kim S.K., 2008. Free radical scavenging activity of a novel antioxidative peptide purified from hydrolysate of bullfrog skin, Rana catesbeiana Shaw. Bioresource Technology, 99(6): 1690-1698.
  31. Rai S., Kamat P.K., Nath C., Shukla R., 2014. Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats. Pharmacology Biochemistry and Behavior, 117: 104-117.
  32. Schoneich C., Hewarathna A., Pal R., Jiang L., Michaelis, E., 2017. Oxidative stress markers of Alzheimer's disease in peripheral cell mitochondria. Free Radical Biology and Medicine, 108: S100.
  33. Selkoe D.J., Hardy J., 2016. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Molecular Medicine, 8(6): 595-608.
  34. Sharma A. D., Kaur, I., 2020. Eucalyptol (1, 8 cineole) from eucalyptus essential Oil a potential inhibitor of COVID 19 corona virus infection by molecular docking studies. Preprint, 2020: 2020030455 .
  35. Teixeira A.L., Reis H.J., Coelho F.M., Carneiro D.S., Teixeira M.M., Vieira L.B., Mukhamedyarov M.A., Zefirov A.L., Janka Z., Palotás A., 2008. All-or-nothing type biphasic cytokine production of human lymphocytes after exposure to Alzheimer's β-amyloid peptide. Biological Psychiatry, 64(10): 891-895.
  36. Tine Y., Diallo A., Diop A., Costa J., Boye C.S.B., Wélé A., Paolini J., 2020. The Essential oil of Eucalyptus alba L. Growing on the Salt Zone of Fatick (Senegal) as a Source of 1, 8- Cineole and Their Antibacterial Activity. Journal of Drug Delivery and Therapeutics, 10(1-s): 140-143.
  37. Tönnies E., Trushina E., 2017. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. Journal of Alzheimer's Disease, 57(4): 1105-1121.
  38. Tramutola A., Lanzillotta C., Perluigi M., Butterfield D.A., 2017. Oxidative stress, protein modification and Alzheimer disease. Brain Research Bulletin, 133: 88-96.
  39. Turunc Bayrakdar E., Uyanikgil Y., Kanit L., Koylu E., Yalcin A., 2014. Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ (1–42)-induced rat model of Alzheimer's disease. Free Radical Research, 48(2): 146-158.
  40. Wang L., Zhao C.Z., 2016. Effect of 1, 8-cineol pretreatment on inflammatory response induced by Aβ_ (25~35) in primary cultured cortical neurons. Chinese Journal of Gerontology, 7: 2.
  41. Zhang Y., Dong H., Liu X., Huang M., 2018. The efficacy of butylphthalide soft capsules combined with donepezil tablet in patients with alzheimer disease and its effect on Serum A beta, GSH-Px and SOD. Pharmaceutical Bioprocessing, 6(1): 21-27.