Chronic treatment with coenzyme Q10 mitigates the behavioral dysfunction of global cerebral ischemia/reperfusion injury in rats

Document Type : Original Article

Authors

1 Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran

2 Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

3 Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

4 Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Objective(s): The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats. 
Materials and Methods: Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities. 
Results: Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals. 
Conclusion: Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Keywords

References

1.     Ahad MA, Kumaran KR, Ning T, Mansor NI, Effendy MA, Damodaran T, et al., Insights into the neuropathology of cerebral ischemia and its mechanisms. Rev Neurosci 2020; 31: 521-538.
2.     Fatemi I, Saeed-Askari P, Hakimizadeh E, Kaeidi A, Esmaeil-Moghaddam S, Pak-Hashemi M, et al., Long-term metformin therapy improves neurobehavioral functions and antioxidative activity after cerebral ischemia/reperfusion injury in rats. Brain Res Bull 2020; 163: 65-71.
3.     Sharma D, Maslov LN, Singh N, and Jaggi AS, Remote ischemic preconditioning-induced neuroprotection in cerebral ischemia-reperfusion injury: Preclinical evidence and mechanisms. Eur J Pharmacol 2020: 173380.
4.     Hakimizadeh E, Shamsizadeh A, Roohbakhsh A, Arababadi MK, Hajizadeh MR, Shariati M, et al., TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats. Iran J Basic Med Sci 2017; 20: 863-869.
5.     Lindblom RPF, Tovedal T, Norlin B, Hillered L, Englund E,  Thelin S. Mechanical reperfusion following prolonged global cerebral ischemia attenuates brain injury. J Cardiovasc Transl Res 2020.
6.     Alimohamadi R, Fatemi I, Naderi S, Hakimizadeh E, Rahmani MR, and Allahtavakoli M, Protective effects of Vitex agnus-castus in ovariectomy mice following permanent middle cerebral artery occlusion. Iran J Basic Med Sci 2019; 22: 1097-1101.
7.     Farhadi Moghadam B and Fereidoni M, Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat. PLoS One 2020; 15: e0229769.
8.     Salehi C, Seiiedy M, Soraya H, Fazli F, and Ghasemnejad-Berenji M, Pretreatment with bisoprolol and vitamin E alone or in combination provides neuroprotection against cerebral ischemia/reperfusion injury in rats. Naunyn Schmiedebergs Arch Pharmacol 2021; 394: 685-695.
9.     Hassonizadeh Falahieh K, Sarkaki A, Edalatmanesh M, Gharib Naseri MK, and Farbood Y, Ellagic acid attenuates post-cerebral ischemia and reperfusion behavioral deficits by decreasing brain tissue inflammation in rats. Iran J Basic Med Sci 2020; 23: 645-653.
10.    Turunen M, Olsson J, and Dallner G, Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004; 1660: 171-199.
11.    Akbari A, Mobini GR, Agah S, Morvaridzadeh M, Omidi A, Potter E, et al., Coenzyme Q10 supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials. Eur J Clin Pharmacol 2020; 76:1483-1499.
12.    Nagib MM, Tadros MG, Rahmo RM, Sabri NA, Khalifa AE, and Masoud SI, Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway. Neurotox Res 2019; 35: 451-462.
13.    Attia H, Albuhayri S, Alaraidh S, Alotaibi A, Yacoub H, Mohamad R, et al., Biotin, coenzyme Q10, and their combination ameliorate aluminium chloride-induced Alzheimer’s disease via attenuating neuroinflammation and improving brain insulin signaling. J Biochem Mol Toxicol 2020: e22519.
14.    Park HW, Park CG, Park M, Lee SH, Park HR, Lim J, et al., Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson’s disease rat model. Sci Rep 2020; 10: 1-12.
15.    Grieb P, Ryba MS, Sawicki J, and Chrapusta SJ, Oral coenzyme Q10 administration prevents the development of ischemic brain lesions in a rabbit model of symptomatic vasospasm. Acta Neuropathol 1997; 94: 363-368.
16.    Yi YY, Shin HJ, Choi SG, Kang JW, Song HJ, Kim SK, et al., Preventive effects of neuroprotective agents in a neonatal rat of photothrombotic stroke model. Int J Mol Sci 2020; 21.
17.    Belousova M, Tokareva OG, Gorodetskaya E, Kalenikova EI, and Medvedev OS, Intravenous treatment with coenzyme Q10 improves neurological outcome and reduces infarct volume after transient focal brain ischemia in rats. J Cardiovasc Pharmacol 2016; 67: 103-109.
18.    Li H, Klein G, Sun P, and Buchan AM, CoQ10 fails to protect brain against focal and global ischemia in rats. Brain Res 2000; 877: 7-11.
19.    Özalp B, Elbey H, Aydın H, Tekkesin MS, and Uzun H, The effect of coenzyme Q10 on venous ischemia reperfusion injury. J Surg Res 2016; 204: 304-310.
20.    Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F, et al., Visfatin reduces hippocampal CA1 cells death and improves learning and memory deficits after transient global ischemia/reperfusion. Neuropeptides 2015; 49: 63-68.
21.    Fatemi I, Delrobaee F, Bahmani M, Shamsizadeh A, and Allahtavakoli M, The effect of the anti-diabetic drug metformin on behavioral manifestations associated with ovariectomy in mice. Neurosci Lett 2019; 690: 95-98.
22.    Hakimizadeh E, Kaeidi A, Taghipour Z, Mehrzadi S, Allahtavakoli M, Shamsizadeh A, et al., Ceftriaxone improves senile neurocognition damages induced by D-galactose in mice. Iran J Basic Med Sci 2020; 23: 368-375.
23.    Rahmati B, Kiasalari Z, Roghani M, Khalili M, and Ansari F, Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats. Pharm Biol 2017; 55: 958-965.
24.    Hughes RN, The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev 2004; 28: 497-505.
25.    Mozafari N, Shamsizadeh A, Fatemi I, Allahtavakoli M, Moghadam-Ahmadi A, Kaviani E, et al., CX691 as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer’s disease.  Iran J Basic Med Sci 2018; 21: 724-730.
26.    Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, et al., Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 2008; 7: 2769-2773.
27.    Kaviani E, Rahmani M, Kaeidi A, Shamsizadeh A, Allahtavakoli M, Mozafari N, et al., Protective effect of atorvastatin on d-galactose-induced aging model in mice. Behav Brain Res 2017; 334: 55-60.
28.    Shadman J, Sadeghian N, Moradi A, Bohlooli S, and Panahpour H, Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats. Metab Brain Dis 2019; 34:1221-1229.
29.    Fatemi I, Khaluoi A, Kaeidi A, Shamsizadeh A, Heydari S, and Allahtavakoli MA, Protective effect of metformin on D-galactose-induced aging model in mice. Iran J Basic Med Sci 2018; 21: 19-25.
30.    Fatemi I, Heydari S, Kaeidi A, Shamsizadeh A, Hakimizadeh E, Khaluoi A, et al., Metformin ameliorates the age-related changes of d-galactose administration in ovariectomized mice. Fundam Clin Pharmacol 2018; 32: 392-399.
31.    Enzmann G, Kargaran S, and Engelhardt B, Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function. Ther Adv Neurol Disord 2018; 11: 1756286418794184.
32.    Siti HN, Kamisah Y, and Kamsiah J, The role of oxidative stress, anti-oxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015; 71: 40-56.
33.    Chang CY, Chen JY, Wu MH, and Hu ML, Therapeutic treatment with vitamin C reduces focal cerebral ischemia-induced brain infarction in rats by attenuating disruptions of blood brain barrier and cerebral neuronal apoptosis. Free Radic Biol Med 2020; 155: 29-36.
34.    Yang J, Yuan L, Wen Y, Zhou H, Jiang W, Xu D, et al., Protective effects of naringin in cerebral infarction and its molecular mechanism. Med Sci Monit 2020; 26: e918772.
35.    Ayoobi F, Shamsizadeh A, Fatemi I, Vakilian A, Allahtavakoli M, Hassanshahi G, et al., Bio-effectiveness of the main flavonoids of Achillea millefolium in the pathophysiology of neurodegenerative disorders- a review. Iran J Basic Med Sci 2017; 20: 604-612.
36.    Onaolapo OJ, Odeniyi AO, Jonathan SO, Samuel MO, Amadiegwu D, Olawale A, et al., An investigation of the anti-Parkinsonism potential of co-enzyme Q10 and co-enzyme Q10 /levodopa-carbidopa combination in mice. Curr Aging Sci 2019; 14:62-75.
37.    Ibrahim Fouad G. Combination of omega 3 and coenzyme Q10 exerts neuroprotective potential against hypercholesterolemia-induced alzheimer’s-like disease in rats. Neurochem Res 2020; 45: 1142-1155.
38.    Kumar A, Pareek V, Faiq MA, Kumar P, Raza K, Prasoon P, et al., Regulatory role of NGFs in neurocognitive functions. Rev Neurosci 2017; 28: 649-673.
39.    Kowianski P, Lietzau G, Czuba E, Waskow M, Steliga A, Morys J. BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 2017; 38:579-593.
40.    Beeri MS and Sonnen J, Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. Neurology 2016; 86: 702-703.
41.    Abuelezz SA, Hendawy N, and Magdy Y, The potential benefit of combined versus monotherapy of coenzyme Q10 and fluoxetine on depressive-like behaviors and intermediates coupled to Gsk-3β in rats. Toxicol Appl Pharmacol 2018; 340: 39-48.
42.    Milanlioglu A, Aslan M, Ozkol H, Cilingir V, Nuri Aydin M, and Karadas S, Serum anti-oxidant enzymes activities and oxidative stress levels in patients with acute ischemic stroke: influence on neurological status and outcome. Wien Klin Wochenschr 2016; 128: 169-174.
43.    Liu Z, Cai Y, Zhang X, Zhu Z, and He J, High serum levels of malondialdehyde and antioxidant enzymes are associated with post-stroke anxiety. Neurol Sci 2018; 39: 999-1007.
44.    Jiao L, Zhang J, Li Z, Liu H, Chen Y, and Xu S, Edaravone alleviates delayed neuronal death and long-dated cognitive dysfunction of hippocampus after transient focal ischemia in Wistar rat brains. Neuroscience 2011; 182: 177-183.
45.    Nabavi SF, Habtemariam S, Di Lorenzo A, Sureda A, Khanjani S, Nabavi SM, et al. Post-stroke depression modulation and in vivo antioxidant activity of gallic acid and its synthetic derivatives in a murine model system. Nutrients 2016; 8:1-13.
46.    Gupta V, Dhull DK, Joshi J, Kaur S, and Kumar A, Neuroprotective potential of azilsartan against cerebral ischemic injury: Possible involvement of mitochondrial mechanisms. Neurochem Int 2020; 132: 104604.
47.    Yang M, Lian N, Yu Y, Wang Y, Xie K, and Yu Y, Coenzyme Q10 alleviates sevoflurane‑induced neuroinflammation by regulating the levels of apolipoprotein E and phosphorylated tau protein in mouse hippocampal neurons. Mol Med Rep 2020; 22: 445-453.
48.    Wu HS, Guo PP, Jin Z, Li XY, Yang X, Ke JJ, et al., Effects of lipoxin a4 pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion. Curr Med Sci 2018; 38: 666-671.
49.    Salehpour F, Farajdokht F, Mahmoudi J, Erfani M, Farhoudi M, Karimi P, et al., Photobiomodulation and coenzyme Q10 treatments attenuate cognitive impairment associated with model of transient global brain ischemia in artificially aged mice. Front Cell Neurosci 2019; 13: 1-17.
50.    Soleimani M, Golab F, Alizadeh A, Rigi S, Samani ZN, Vahabzadeh G, et al., Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q(10) on hippocampal injury in mouse. J Cell Physiol 2019; 234: 18720-18730.
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 1
January 2022
Pages 39-45

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