مجله علوم پزشکی پارس
اثر کوانزیم Q10 بر التهاب عصبی و آسیب سلولی هیپوکامپ در مدل مسمومیت تحریکی با مونوسدیم گلوتامات
نویسندگان
1 دانشجوی کارشناسی ارشد،گروه زیست شناسی، دانشکده علوم، واحد شیراز، دانشگاه آزاداسلامی، شیراز، ایران
2 دانشیار، گروه زیست شناسی، دانشکده علوم، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران
چکیده
مقدمه: مونوسدیم گلوتامات (MSG) سبب القاء سمیت تحریکی و آسیب سلولی در نواحی مختلف مغز به ویژه هیپوکامپ می‌گردد. مطالعه حاضر به ارزیابی اثر ضد التهابی و حفاظت عصبی کوانزیم Q10 (Co-Q10) بر آسیب سلولی هیپوکامپ در موش‌های صحرایی تحت تیمار با MSG می‌پردازد.
روش کار: تعداد 40 سر موش صحرایی نر بالغ نژاد ویستار به صورت تصادفی در 4 گروه کنترل، MSG+Q10-10 ، MSG و MSG+Q10-20 قرار گرفتند. MSG (gr/kg 3، به روش دهانی) و Co-Q10 (mg/kg 20 و mg/kg 10، درون صفاقی) روزانه و به مدت 4 هفته تجویز شد. پس از 4 هفته، حیوانات قربانی شدند و هیپوکامپ مغز به سرعت بر روی یخ جدا شد. سطح هیپوکامپی فاکتور نکروز دهنده توموری آلفا (TNF-α)، اینترلوکین 1 بتا (IL-1β) و اینترلوکین 6 (IL-6) به روش الایزا ارزیابی شد و در پایان، تراکم نورون‌های تیره در نواحی مختلف هیپوکامپ به روش استرئولوژی سنجیده شد.
یافته ها: در مقایسه با گروه MSG، تیمار با Co-Q10 سبب کاهش معنا‌دار فاکتورهای التهابی ( TNF-α، IL-1ß و IL-6) در هیپوکامپ موش‌های صحرایی گروه‌های تیمار با Co-Q10 گردید (p<0.05). تراکم نورون‌های تیره در نواحی CA3، CA2، CA1 و ژیروس دندانه ای هیپوکامپ در گروه‌های دریافت کننده Co-Q10 در مقایسه با گروه MSG کاهش معناداری داشت (p<0.05).
نتیجه‌گیری: ویژگی ضد التهابی کوانزیم Q10 احتمالاً مسئول عملکرد حفاظت عصبی آن در هیپوکامپ است و سمیت عصبی ناشی از MSG را در موش‌های صحرایی بهبود می‌بخشد.
کلیدواژه‌ها
عنوان مقاله [English]
The effect of coenzyme-Q10 on neuroinflammation and hippocampal cell damage in a model of monosodium glutamate induced excitotoxicity
نویسندگان [English]
- Zeynab Abutalebi Ardakani 1
- Mohammad Amin Edalatmanesh 2
1 MSc. Student, Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2 Associate Professor, Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
چکیده [English]
Introduction: Monosodium glutamate (MSG) induces excitotoxicity and cell damage in different areas of the brain, especially the hippocampus. The present study evaluated the anti-inflammatory and neuroprotective effects of coenzyme Q10 (Co-Q10) on hippocampal cell damage in MSG-treated rats.
Materials and Methods: Forty adult male Wistar rats were randomly divided into 4 groups: control, MSG, MSG+Q10-10 and MSG+Q10-20. MSG (3 gr/kg, orally) and Co-Q10 (20 mg/kg and 10 mg/kg, intraperitoneally) were administered day after day for 4 weeks. After 4 weeks, the animals were sacrificed and the brain hippocampus was isolated quickly on ice. Hippocampal levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were estimated by ELISA technique. Finally, the density of dark neurons in different areas of the hippocampus was measured by stereology method.
Results: In comparison with MSG group, Co-Q10 treatment significantly reduced inflammatory factors (TNF-α, IL-1β and IL-6) in the hippocampus of Co-Q10-treated rats (p<0.05). The density of dark neurons in CA1, CA2, CA3 and dentate gyrus regions of the hippocampus was significantly reduced in the Co-Q10 group compared with the MSG group (p˂0.05).
Conclusion: The anti-inflammatory properties of coenzyme Q10 may be responsible for its neuroprotective function
in the hippocampus and ameliorates MSG-induced neurotoxicity in rats.
کلیدواژه‌ها [English]
- Ubiquinone
- Monosodium glutamate
- Hippocampus
- Inflammation
- Rat
Nutrients. 2020;12(4):1028.2. Vorhees CV. A Test of Dietary MonosodiumGlutamate Developmental Neurotoxicity in Rats: AReappraisal. Ann Nutr Metab. 2018;73 Suppl 5:36-42.3. Lobine D, Sadeer N, Jugreet S, Suroowan S, Keenoo
BS, Imran M, et al. Potential of medicinal plants asneuroprotective and therapeutic properties againstamyloid-β-related toxicity, and glutamate-inducedexcitotoxicity in human neural cells. CurrNeuropharmacol. 2021.4. Fernstrom JD. Monosodium Glutamate in the DietDoes Not Raise Brain Glutamate Concentrations orDisrupt Brain Functions. Ann Nutr Metab. 2018;73Suppl 5:43-52.5. Pisanò CA, Brugnoli A, Novello S, Caccia C,Keywood C, Melloni E, et al. Safinamide inhibits invivo glutamate release in a rat model of Parkinson'sdisease. Neuropharmacology. 2020; 167:108006.6. Yousof SM, Awad YM, Mostafa EMA, Hosny MM,Anwar MM, Eldesouki RE, et al. The potentialneuroprotective role of Amphora coffeaeformis algaeagainst monosodium glutamate-induced neurotoxicityin adult albino rats. Food Funct. 2021;12(2):706-716.7. Helal AM, Abdel-Latif MS, Abomughaid MM,
Ghareeb DA, El-Sayed MM. Potential therapeuticeffects of Ulva lactuca water fraction on monosodiumglutamate-induced testicular and prostatic tissuedamage in rats. Environ Sci Pollut Res Int. 2021;28(23):29629-29642.8. Cappellano G, Vecchio D, Magistrelli L, Clemente N,Raineri D, Barbero Mazzucca C, et al. The Yin-Yangof osteopontin in nervous system diseases: damageversus repair. Neural Regen Res. 2021;16(6):1131-37.9. Navas P, Cascajo MV, Alcázar-Fabra M, Hernández-Camacho JD, Sánchez-Cuesta A, Rodríguez ABC, etal. Secondary CoQ10 deficiency, bioenergeticsunbalance in disease and aging. Biofactors. 2021;10(11): 1785.10. Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, Barriocanal-Casado, LópezrradorS,QuinziiCM,LópezLC.MetabolicTargetsofCoenzymeQ10inMitochondria.Antioxidants(Basel).2021;10(4):520.11. Hassanzadeh S, Jameie SB, Soleimani M, FarhadiM, Kerdari M, Danaei N. Coenzyme Q10 Influenceson the Levels of TNF-α and IL-10 and the Ratio ofBax/Bcl2 in a Menopausal Rat Model Following 071145Lumbar Spinal Cord Injury. J Mol Neurosci.2018;65(2):255-64.12. Rahimi Anbarkeh F, Baradaran R, Ghandy N, JalaliM, Reza Nikravesh M, Soukhtanloo M. Effects ofmonosodium glutamate on apoptosis of germ cells intesticular tissue of adult rat: An experimental study.Int J Reprod Biomed. 2019;17(4):261–70.13. Gholipour F, Shams J, Zahiroddin A. ProtectiveEffect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats. Novel Biomed2017; 5(3), 127-32.14. Mazloom BF, Edalatmanesh MA, Hosseini SE.Gallic acid reduces inflammatory cytokines andmarkers of oxidative damage in a rat model ofestradiol-induced polycystic ovary. Comp Clin Pathol.2019; 28:1281–86.15. Baghishani F, Mohammadipour A, Hosseinzadeh H,Hosseini M, Ebrahimzadeh-Bideskan A. The effectsof tramadol administration on hippocampal cellapoptosis, learning and memory in adult andneuroprotective effects of crocin. Metab Brain Dis.2018;33(3):907-16.16. Seghatoleslam M, Alipour F, Shafieian R, et al. Theeffects of Nigella sativa on neural damage afterpentylenetetrazole induced seizures in rats. J TraditComplement Med. 2015; 6(3):262-8.17. Shukry M, El-Shehawi AM, El-Kholy WM, ElsisyRA, Hamoda HS, Tohamy HG, et al. AmeliorativeEffect of Graviola (Annona muricata) on MonoSodium Glutamate-Induced Hepatic Injury in Rats:Antioxidant, Apoptotic, Anti-inflammatory,Lipogenesis Markers, and Histopathological Studies.Animals (Basel). 2020;10(11):1996.18. Xu L, Sun J, Lu R, Ji Q, Xu JG. Effect of glutamateon inflammatory responses of intestine and brain afterfocal cerebral ischemia. World J Gastroenterol.2005;11(5):733-6.19. Pagano J, Giona F, Beretta S, Verpelli C, Sala C. N-methyl-d-aspartate receptor function in neuronal andsynaptic development and signaling. Curr OpinPharmacol. 2021; 56:93-101.20. Sanabria ER, Pereira MF, Dolnikoff MS, AndradeIS, Ferreira AT, Cavalheiro EA, et al. Deficit inhippocampal long-term potentiation in monosodiumglutamate-treated rats. Brain Res Bull. 2002;59(1):47-51.21. Jin L, Li YP, Feng Q, Ren L, Wang F, Bo GJ, et al.Cognitive deficits and Alzheimer-likeneuropathological impairments during adolescence ina rat model of type 2 diabetes mellitus. Neural RegenRes. 2018;13(11):1995-2004.22. Rodrigues KC, Bortolatto CF, da Motta KP, deOliveira RL, Paltian JJ, Krüger R, et al. Theneurotherapeutic role of a selenium-functionalizedquinoline in hypothalamic obese rats.Psychopharmacology (Berl). 2021; 238(7):1937-1951.23. Gonçalves-Ribeiro J, Pina CC, Sebastião AM, VazSH. Glutamate Transporters in HippocampalLTD/LTP: Not Just Prevention of Excitotoxicity.Front Cell Neurosci. 2019; 13:357.24. Frankola KA, Greig NH, Luo W, Tweedie D.Targeting TNF-α to elucidate and ameliorateneuroinflammation in neurodegenerative diseases.CNS Neurol Disord Drug Targets. 2011; 10(3):391-403.25. Verhoog QP, Holtman L, Aronica E, van Vliet EA.Astrocytes as Guardians of Neuronal Excitability:Mechanisms Underlying Epileptogenesis. FrontNeurol. 2020;11:591690.26. Sprague AH, Khalil RA. Inflammatory cytokines invascular dysfunction and vascular disease. BiochemPharmacol. 2009;78(6):539-552.27. Kany S, Vollrath JT, Relja B. Cytokines inInflammatory Disease. Int J Mol Sci.2019;20(23):6008.28. Salehpour F, Farajdokht F, Cassano P, Sadigh-Eteghad S, Erfani M, Hamblin MR, et al. Near-infrared photobiomodulation combined withcoenzyme Q10 for depression in a mouse model ofrestraint stress: reduction in oxidative stress,neuroinflammation, and apoptosis. Brain Res Bull.2019; 144:213-22.29. Suárez-Rivero JM, Pastor-Maldonado CJ, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I,Munuera-Cabeza M, et al. Coenzyme Q10 Analogues:Benefits and Challenges for Therapeutics.Antioxidants (Basel). 2021;10(2):236.30. Kones R. Mitochondrial therapy for Parkinson'sdisease: neuroprotective pharmaconutrition may bedisease-modifying. Clin Pharmacol. 2010; 2:185-98.doi:10.2147/CPAA.S12082.31. Singh A, Kumar A. Microglial InhibitoryMechanism of Coenzyme Q10 Against Aβ (1-42)Induced Cognitive Dysfunctions: Possible Behavioral,Biochemical, Cellular, and HistopathologicalAlterations. Front Pharmacol. 2015; 6:268.32. Sharma SK, El Refaey H, Ebadi M. Complex-1activity and 18F-DOPA uptake in geneticallyengineered mouse model of Parkinson's disease andthe neuroprotective role of coenzyme Q10. Brain ResBull. 2006;70(1):22-3233. Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia inAlzheimer's disease. Ann Transl Med.2015;3(10):136.34. Zhou Y, Danbolt NC. Glutamate as aneurotransmitter in the healthy brain. J Neural Transm(Vienna). 2014;121(8):799-817.35. Zsombok A, Toth Z, Gallyas F. Basophilia,acidophilia and argyrophilia of “dark” (compactedneurons during their formation, recovery or death inan otherwise undamaged environment. J NeurosciMethods. 2005;142(1):145e15
)