Fullerenol Nanoparticles Decrease Brain Infarction Through Potentiation of Superoxide Dismutase Activity During Cerebral Ischemia-Reperfusion Injury

Authors

Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

10.17795/rijm41736

Abstract

Abstract Background: Ithasbeendemonstratedthatweakening of thebrainantioxidant systemandoxidative stress is themaincontributor in pathophysiology of ischemic stroke. Objectives: Since fullerenol nanoparticles have powerful antioxidant effects in biological environments, we aimed to evaluate whether fullerenol administration during cerebral ischemia potentiates the antioxidant defense systemof ischemic brain and de- creases cerebral infarction. Methods: Thirty six rats were randomly divided into three groups (n = 12 for each group): sham, control ischemia and ischemic treatment groups. Themiddle cerebral artery (MCA) was obstructed for 90minutes in right hemispheres of control ischemia and ischemic treatment groups to achieve the experimentalmodel of ischemic stroke. Treated rats received fullerenol nanoparticles (10 mg/kg, intraperitoneally) 30minutes beforeMCA occlusion. Brain infarction, glutathione content and superoxide dismutase (SOD) activity were determined at the end of experiment. Results: Occlusion of MCA induced considerable infarction and lesion in ischemic hemispheres of control ischemic rats (52759 mm3 ) in accompany with a decrease in the glutathione content (45%), and SOD activity (29%) compared with sham rats. Adminis- tration of fullerenol in ischemic treatment group before MCA occlusion reduced the value of infarction (138  67 mm3 ) and also increased the value of the SOD activity by 33% compared to control ischemic group. Conclusions: Our findings indicate that fullerenol nanoparticles decrease the brain infarction through enhancement of the SOD activity during cerebral ischemia-reperfusion injury.

Keywords


  1. 1.Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, et al. Oxidative stress in ischemic brain damage: mechanisms of cell death Razavi Int J Med. 2016; 4(4):e41736. 5 Darabi S et al. and potential molecular targets for neuroprotection. Antioxid Redox Signal. 2011;14(8):1505–17. doi: 10.1089/ars.2010.3576. [PubMed: 20812869].

    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(5):698–714. [PubMed: 23469845].
    2. Olmez I, Ozyurt H. Reactive oxygen species and ischemic cerebrovascular disease. Neurochem Int. 2012;60(2):208–12. doi: 10.1016/j.neuint.2011.11.009. [PubMed: 22122807].
    3. Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem. 2008;15(4):404–14. [PubMed: 18288995].
    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(2):163–70. [PubMed: 12067499].
    5. Injac R, Prijatelj M, Strukelj B. Fullerenol nanoparticles: toxicity and antioxidant activity. Methods Mol Biol. 2013;1028:75–100. doi: 10.1007/978-1-62703-475-3_5. [PubMed: 23740114].
    6. 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(4):600– 7. doi: 10.1002/1097-4547(20001115)62:4<_x0036_00:_x003a_AID-JNR15>3.0.CO;2-F. [PubMed: 11070504].
    7. Bisaglia M, Natalini B, Pellicciari R, Straface E, Malorni W, Monti D, et al. C3-fullero-tris-methanodicarboxylic acid protects cerebellar granule cells from apoptosis. J Neurochem. 2000;74(3):1197–204. [PubMed: 10693952].
    8. Cai X, Hao J, Zhang X, Yu B, Ren J, Luo C, et al. The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizingradiation-induced immune and mitochondrial dysfunction. Toxicol Appl Pharmacol. 2010;243(1):27–34. doi: 10.1016/j.taap.2009.11.009. [PubMed: 19914272]. 10. Bogdanovic V, Stankov K, Icevic I, Zikic D, Nikolic A, Solajic S, et al. Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. J Radiat Res. 2008;49(3):321–7. [PubMed: 18285660].
    9. Trajkovic S, Dobric S, Jacevic V, Dragojevic-Simic V, Milovanovic Z, Dordevic A. Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces. 2007;58(1):39– 43. doi: 10.1016/j.colsurfb.2007.01.005. [PubMed: 17317115].
    10. 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(6):298–305. doi: 10.3109/15376516.2010.485622. [PubMed: 20491520].
    11. Xu JY, Su Y, Cheng JS, Li SX, Liu R, Li WX, et al. Protective effects of fullerenol on carbon tetrachloride-induced acute hepatotoxicity and nephrotoxicity in rats. Carbon. 2010;48(5):1388–96. 14. Yin JJ, Lao F, Meng J, Fu PP, Zhao Y, Xing G, et al. Inhibition of tumor growth by endohedral metallofullerenol nanoparticles optimized as reactive oxygen species scavenger. Mol Pharmacol. 2008;74(4):1132–40. doi: 10.1124/mol.108.048348. [PubMed: 18635669].
    12. Cai X, Jia H, Liu Z, Hou B, Luo C, Feng Z, et al. Polyhydroxylated fullerene derivative C(60)(OH)(24) prevents mitochondrial dysfunction and oxidative damage in an MPP(+) -induced cellular model of Parkinson’s disease. J Neurosci Res. 2008;86(16):3622–34. doi: 10.1002/jnr.21805. [PubMed: 18709653].
    13. 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-I membrane expression and apoptosis in vitro. Int J Nanomedicine. 2008;3(1):59–68. [PubMed: 18488416].
    14. Silva GA. Nanotechnology approaches for the regeneration and neuroprotection of the central nervous system. Surg Neurol. 2005;63(4):301–6. doi: 10.1016/j.surneu.2004.06.008. [PubMed: 15808703].
    15. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91. [PubMed: 2643202].
    16. 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(1):43–9. doi: 10.1016/j.prp.2014.07.014. [PubMed: 25441658].
    17. Tietz F. Enzymic method for quantitatve determination of nanogram amount of total and oxidized glutathione: applications to mammalian blood and other tissues. Biocham. 1969;27:502–22. 21. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6. [PubMed: 6727660].
    18. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem. 1976;72:248–54. [PubMed: 942051].
    19. 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. doi: 10.2147/IJN.S56973. [PubMed: 24812508].
    20. Hu Z, Huang Y, Guan W, Zhang J, Wang F, Zhao L. The protective activities of water-soluble C(60) derivatives against nitric oxideinduced cytotoxicity in rat pheochromocytoma cells. Biomaterials. 2010;31(34):8872–81. doi: 10.1016/j.biomaterials.2010.08.025. [PubMed: 20813403].
    21. Markovic Z, Trajkovic V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials. 2008;29(26):3561–73. doi: 10.1016/j.biomaterials.2008.05.005. [PubMed: 18534675].
    22. 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(4):611–21. doi: 10.1016/j.biomaterials.2008.09.061. [PubMed: 18986699].
    23. Rowley S, Patel M. Mitochondrial involvement and oxidative stress in temporal lobe epilepsy. Free Radic Biol Med. 2013;62:121–31. doi: 10.1016/j.freeradbiomed.2013.02.002. [PubMed: 23411150].
    24. 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. doi: 10.1155/2015/426069. [PubMed: 25722793].