Abstract
Fullerol compounds have potent antioxidant effects on biological systems. Therefore, we examined whether fullerol pretreatment potentiates the brain antioxidant defense system and decreases γ-glutamyl transpeptidase (GGT) expression during cerebral ischemia/reperfusion. Experiments were performed in three groups of rats: sham, control ischemic, and ischemic pretreatment groups. Brain ischemia was induced by 90 min of middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Rats received fullerol nanoparticles (10 mg/kg, intraperitoneally) 30 min before MCAO. Brain infarction, mRNA levels of GGT, glutathione content, and catalase activity were determined after 24 h reperfusion. MCAO induced extensive lesions in the right hemispheres of the control ischemic group (infarct volume 522±54 mm3) and a concomitant reduction of the glutathione content (45%) and catalase activity (56%) compared to the sham group. Fullerol in the ischemic pretreatment group significantly decreased the infarct volume (133±62 mm3) and also increased the activity of catalase by 53% compared to control. MCAO additionally increased the mRNA levels of GGT in ischemic hemispheres; however, fullerol considerably decreased the mRNA levels of this gene in the pretreatment group. The findings of the present study indicate that fullerol nanoparticles protect the ischemic brain against ischemia/reperfusion injury through potentiation of the antioxidant defense system and attenuation of GGT expression.
About the authors
Shamsi Darabi obtained her PhD in physiology from Baqiyatallah University of Medical Sciences (2016). She did her thesis under the guidance of Dr. M.T. Mohammadi for her PhD degree. In her thesis, she studied the effects of fullerol nanoparticles on ischemic stroke. She has published over five peer-reviewed scientific papers from this thesis. She currently works in Qom University of Medical Sciences. She is working on new projects focusing on traditional medicine and also Islamic and Iranian medicine.
Mohammad Taghi Mohammadi obtained his PhD in physiology from Shiraz University of Medical Sciences (2011). He joined the University of Baqiyatallah Medical Sciences in 2011. He is the associate professor of physiology in the Faculty of Medicine. Currently, he is the head of the Department of Physiology and Biophysics. He teaches physiology to medical students, pharmacy students, MSc, and PhD students. Dr. Mohammadi has published over 45 peer-reviewed scientific papers. He is currently working on new projects focusing on basic research in the fields of ischemic stroke, cardiovascular diseases, and diabetes mellitus complications such as diabetic nephropathy.
Acknowledgment
The authors warmly appreciate the financial support of the Vice Chancellor for Research of the University of Baqiyatallah Medical Sciences, Tehran, Iran.
Conflict of interest statement: The authors state no conflict of interest. All authors have read the journal’s publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.
References
1. Rodrigo R, Fernandez-Gajardo R, Gutierrez R, Matamala JM, Carrasco R, Miranda-Merchak A, et al. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. CNS Neurol Disord Drug Targets 2013;12: 698–714.10.2174/1871527311312050015Search in Google Scholar
2. Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, et al. Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal 2011;14:1505–17.10.1089/ars.2010.3576Search in Google Scholar
3. Slemmer JE, Shacka JJ, Sweeney M, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 2008;15:404–14.10.2174/092986708783497337Search in Google Scholar
4. Nita DA, Nita V, Spulber S, Moldovan M, Popa DP, Zagrean AM, et al. Oxidative damage following cerebral ischemia depends on reperfusion‐a biochemical study in rat. J Cell Mol Med 2001;5:163–70.10.1111/j.1582-4934.2001.tb00149.xSearch in Google Scholar
5. Olmez I, Ozyurt H. Reactive oxygen species and ischemic cerebrovascular disease. Neurochem Int 2012;60:208–12.10.1016/j.neuint.2011.11.009Search in Google Scholar
6. Gurbuzer N, Gozke E, Ayhan Basturk Z. Gamma-glutamyl transferase levels in patients with acute ischemic stroke. Cardiovasc Psychiatry Neurol 2014;2014:1–4.10.1155/2014/170626Search in Google Scholar
7. Tate SS, Meister A. γ-Glutamyl transpeptidase: catalytic, structural and functional aspects. In: V. A. Najjar editor. The biological effects of glutamic acid and its derivatives. Berlin: Springer; 1981:357–68.10.1007/978-94-009-8027-3_23Search in Google Scholar
8. Zhang H, Forman HJ. Redox regulation of γ-glutamyl transpeptidase. Am J Respir Cell Mol Biol 2009;41:509–15.10.1165/rcmb.2009-0169TRSearch in Google Scholar
9. Zhang H, Forman HJ, Choi J. Gamma-glutamyl transpeptidase in glutathione biosynthesis. Methods Enzymol 2005;401:468–83.10.1016/S0076-6879(05)01028-1Search in Google Scholar
10. Hawkins RA, O’Kane RL, Simpson IA, Vina JR. Structure of the blood-brain barrier and its role in the transport of amino acids. J Nutr 2006;136:218S–26S.10.1093/jn/136.1.218SSearch in Google Scholar PubMed
11. Chistyakov VA, Smirnova YO, Prazdnova EV, Soldatov AV. Possible mechanisms of fullerene C(6)(0) antioxidant action. BioMed Res Int 2013;2013:821498.10.1155/2013/821498Search in Google Scholar
12. Xiao Y, Wiesner MR. Characterization of surface hydrophobicity of engineered nanoparticles. J Hazard Mater 2012;215–6: 146–51.10.1016/j.jhazmat.2012.02.043Search in Google Scholar
13. Wong-Ekkabut J, Baoukina S, Triampo W, Tang IM, Tieleman DP, Monticelli L. Computer simulation study of fullerene translocation through lipid membranes. Nat Nanotechnol 2008;3:363–8.10.1038/nnano.2008.130Search in Google Scholar
14. Cai X, Hao J, Zhang X, Yu B, Ren J, Luo C, et al. The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction. Toxicol Appl Pharmacol 2010;243:27–34.10.1016/j.taap.2009.11.009Search in Google Scholar
15. Bogdanović V, Stankov K, Ičević I, Žikič D, Nikolić A, Šolajić S, et al. Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. J Radiat Res 2008;49:321–7.10.1269/jrr.07092Search in Google Scholar
16. Trajković S, Dobrić S, Jaćević V, Dragojević-Simić V, Milovanović Z, Đorđević A. Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces 2007;58:39–43.10.1016/j.colsurfb.2007.01.005Search in Google Scholar
17. Injac R, Prijatelj M, Strukelj B. Fullerenol nanoparticles: toxicity and antioxidant activity. Methods Mol Biol 2013;1028:75–100.10.1007/978-1-62703-475-3_5Search in Google Scholar
18. Srdjenovic B, Milic-Torres V, Grujic N, Stankov K, Djordjevic A, Vasovic V. Antioxidant properties of fullerenol C60(OH)24 in rat kidneys, testes, and lungs treated with doxorubicin. Toxicol Mech Methods 2010;20:298–305.10.3109/15376516.2010.485622Search in Google Scholar
19. Cai X, Jia H, Liu Z, Hou B, Luo C, Feng Z, et al. Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+‐induced cellular model of Parkinson’s disease. J Neurosci Res 2008;86:3622–34.10.1002/jnr.21805Search in Google Scholar
20. Jin H, Chen WQ, Tang XW, Chiang LY, Yang CY, Schloss JV, et al. Polyhydroxylated C(60), fullerenols, as glutamate receptor antagonists and neuroprotective agents. J Neurosci Res 2000;62:600–7.10.1002/1097-4547(20001115)62:4<600::AID-JNR15>3.0.CO;2-FSearch in Google Scholar
21. Silva GA. Nanotechnology approaches for the regeneration and neuroprotection of the central nervous system. Surg Neurol 2005;63:301–6.10.1016/j.surneu.2004.06.008Search in Google Scholar
22. Gelderman MP, Simakova O, Clogston JD, Patri AK, Siddiqui SF, Vostal AC, et al. Adverse effects of fullerenes on endothelial cells: fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro. Int J Nanomedicine 2008;3:59–68.10.1182/blood.V108.11.1801.1801Search in Google Scholar
23. Monteiro-Riviere NA, Linder KE, Inman AO, Saathoff JG, Xia XR, Riviere JE. Lack of hydroxylated fullerene toxicity after intravenous administration to female Sprague-Dawley rats. J Toxicol Environ Health A 2012;75:367–73.10.1080/15287394.2012.670894Search in Google Scholar
24. Vani JR, Mohammadi MT, Foroshani MS, Jafari M. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke. EXCLI J 2016;15:378–90.Search in Google Scholar
25. Mohammadi MT, Dehghani GA. Nitric oxide as a regulatory factor for aquaporin-1 and 4 gene expression following brain ischemia/reperfusion injury in rat. Pathol Res Pract 2015;211:43–9.10.1016/j.prp.2014.07.014Search in Google Scholar
26. Tietz F. Enzymic method for quantitative determination of nanogram amount of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 1969;27:502–22.10.1016/0003-2697(69)90064-5Search in Google Scholar
27. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121–6.10.1016/S0076-6879(84)05016-3Search in Google Scholar
28. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.10.1016/0003-2697(76)90527-3Search in Google Scholar
29. Ye S, Chen M, Jiang Y, Chen M, Zhou T, Wang Y, et al. Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system. Int J Nanomedicine 2014;9:2073–87.10.2147/IJN.S56973Search in Google Scholar PubMed PubMed Central
30. Hu Z, Huang Y, Guan W, Zhang J, Wang F, Zhao L. The protective activities of water-soluble C(60) derivatives against nitric oxide-induced cytotoxicity in rat pheochromocytoma cells. Biomaterials 2010;31:8872–81.10.1016/j.biomaterials.2010.08.025Search in Google Scholar PubMed
31. Markovic Z, Trajkovic V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials 2008;29:3561–73.10.1016/j.biomaterials.2008.05.005Search in Google Scholar PubMed
32. Yin JJ, Lao F, Fu PP, Wamer WG, Zhao Y, Wang PC, et al. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials 2009;30:611–21.10.1016/j.biomaterials.2008.09.061Search in Google Scholar
33. Song J, Park J, Oh Y, Lee JE. Glutathione suppresses cerebral infarct volume and cell death after ischemic injury: involvement of FOXO3 inactivation and Bcl2 expression. Oxid Med Cell Longev 2015;2015:426069.10.1155/2015/426069Search in Google Scholar
34. Kobayashi H, Minami S, Itoh S, Shiraishi S, Yokoo H, Yanagita T, et al. Aquaporin subtypes in rat cerebral microvessels. Neurosci Lett 2001;297:163–6.10.1016/S0304-3940(00)01705-5Search in Google Scholar
35. Korantzopoulos P, Tzimas P, Kalantzi K, Kostapanos M, Vemmos K, Goudevenos J, et al. Association between serum gamma-glutamyltransferase and acute ischemic nonembolic stroke in elderly subjects. Arch Med Res 2009;40:582–9.10.1016/j.arcmed.2009.07.012Search in Google Scholar PubMed
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