J Appl Biomed 14:285-297, 2016 | DOI: 10.1016/j.jab.2016.05.004
Effects of fullerenol nanoparticles and amifostine on radiation-induced tissue damages: Histopathological analysis
- a National Poison Control Centre, Military Medical Academy, Belgrade, Serbia
- b University of Defence in Belgrade, Medical Faculty of the Military Medical Academy, Serbia
- c Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic
- d University of Novi Sad, Faculty of Science, Department of Chemistry, Biochemistry and Environmental Protection, Novi Sad, Serbia
- e Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
- f Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia
- g Institute for Scientific Information, Military Medical Academy, Belgrade, Serbia
- h Alltech, Nicholasville, KY, United States
- i Department for Treatment, Military Medical Academy, Belgrade, Serbia
Fullerenol C60(OH)24 nanoparticles (FNP) are promising radioprotectors in prevention of early and late ionizing radiation injury. The aim of this study was to compare the efficacy of FNP and amifostine (AMI) in protection of rats exposed to whole-body X-ray irradiation (7 or 8 Gy). Both compounds (FNP, 100 mg/kg ip; AMI, 300 mg/kg ip) were given 30 min before irradiation throughout the study. The general radioprotective efficacy of FNP and AMI were evaluated in rats irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival were monitored during the period of 30 days after irradiation. Both compounds were of comparable efficacy. Tissue-protective effects of tested compounds were assessed in rats irradiated with an sublethal dose of X-rays (7 Gy). For this purpose, the animals were sacrificed on the 7th and 28th day after irradiation. Their lung, heart, liver, kidney, small intestine and spleen were taken for histopathological and semiquantitative analysis. Careful examination of established tissue and vascular alteration revealed better radioprotective effects of FNP compared to those of AMI on the small intestine, lung and spleen, while AMI had better radioprotective effects than FNP in protection of the heart, liver and kidney. Results of this study confirmed high radioprotective efficacy of FNP in irradiated rats that was comparable to that of AMI, a well-known radioprotector.
Keywords: X-ray radiation; Tissue damages; Radioprotection; Fullerenol nanoparticles; Amifostine
Received: March 20, 2016; Revised: May 22, 2016; Accepted: May 25, 2016; Published: November 1, 2016 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Babbar, N., Casero, R.A., 2006. Tumor necrosis factor-a increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis. Cancer. Res. 66, 11125- 11130.
Go to original source...
Go to PubMed...
- Beranova, E., Klouda, K., Zeman, K., 2011. C60 Fullerene derivative: influence of nanoparticle size on toxicity and radioprotectivity of water soluble fullerene derivative. Mat. Sci. Eng. A Struct. 1, 948-956.
- Bogdanovic, V., Stankov, K., Icevic, I., Zikic, D., Nikolic, A., Solajic, S., Djordjevic, A., Bogdanovic, G., 2008. Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. J. Radiat. Res. 49, 321- 327.
Go to original source...
Go to PubMed...
- Cai, X., Hao, J., Zhang, X., Yu, B., Ren, J., Luo, C., Li, Q., Huang, Q., Shi, X., Li, W., Liu, J., 2010. The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction. Toxicol. Appl. Pharmacol. 243, 27-34.
Go to original source...
Go to PubMed...
- Cavas, T., Cinkilic, N., Vatan, O., Yilmaz, D., 2014. Effects of fullerenol nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts. Pestic. Biochem. Phys. 114, 1-7.
Go to original source...
Go to PubMed...
- Citrin, D., Cotrim, A.P., Hyodo, F., Baum, B.J., Krishna, M.C., Mitchell, J.B., 2010. Radioprotectors and mitigators of radiation induced normal tissue injury. Oncologist 15, 360-371.
Go to original source...
Go to PubMed...
- De Grey, A.D., 2000. The reductive hotspot hypothesis: an update. Arch. Biochem. Biophys. 373, 295-301.
Go to original source...
Go to PubMed...
- Demiral, A.N., Zerebakan, O., Simsir, V., Alpsoy, E., 2002. Amifostin-induced toxic epidermal necrolysis during radiotherapy: a case report. Jpn. J. Clin. Oncol. 32, 477-479.
Go to original source...
Go to PubMed...
- Djordjevic, A., Canadanovic-Brunet, J.M., Vojinovic-Miloradov, M., Bogdanovic, G., 2004. Antioxidant properties and hypothetic radical mechanism of fullerenol C60(OH)24. Oxid. Commun. 27, 806-812.
- Djordjevic, A., Ajdinovic, B., Dopudja, M., Trajkovic, S., Milovanovic, Z., Maksin, T., Neskovic, O., Bogdanovic, V., Trpkov, Dj., Cveticanin, J., 2011. Scintigraphy of the domestic dog using [99mTc(CO3)(H2O)3]-C60(OH)22-24. Dig. J. Nanomater. Bios. 6, 99-106.
- Dragojevic-Simic, V., Dobric, S., 1996. The cytoprotective agent amifostine (WR2721): current clinical use and trends in its development (in Serbian). Vojnosanit. Pregl. 53, 305-310.
Go to PubMed...
- Dragojevic-Simic, V., Jacevic, V., Dobric, S., Djordjevic, A., Bokonjic, D., Bajcetic, M., Injac, R., 2011. Anti-inflammatory activity of fullerenol C60(OH)24 nano-particles in a model of acute inflammation in rats. Dig. J. Nanomater. Bios. 6, 819-827.
- Foley, S., Crowley, C., Smaihi, M., Bonfils, C., Erlanger, B.F., Seta, P., Larroque, C., 2002. Cellular localization of a water-soluble fullerene derivative. Biochem. Biophys. Res. Comm. 294, 116-119.
Go to original source...
Go to PubMed...
- Giambarresi, L., Jacobs, A.J., 1987. Radioprotectants. In: Conklin, J.J., Walker, R.I. (Eds.), Military Radiobiology.. Academic Press, New York, pp. 265-301.
Go to original source...
- Grdina, D.J., Murley, J.S., Kataoka, Y., Calvin, D.P., 2002. Differential activation of nuclear transcription factor kappaB, gene expression, and proteins by amifostine's free thiol in human microvascular endothelial and glioma cells. Semin. Radiat. Oncol. 12, 103-111.
Go to original source...
Go to PubMed...
- Grebowski, J., Kazmierska, P., Krokosz, A., 2013. Fullerenols as a new therapeutic approach in nanomedicine doi:http://dx.doi.org/10.1155/2013/751913.
- Hall, E.J., Giaccia, A.J., 2011. Radiobiology for Radiologist, seventh ed. Lippincot Williams & Wilkins, Philadelphia.
- Haschek, W.M., Rousseaux, C.G., 1998. Fundamentals of Toxicologic Pathology, second ed. Academic Press, San Diego.
- Indeglia, P.A., Georgieva, A., Krishna, V.B., Bonzongo, J.C.J., 2014. Physicochemical characterization of fullerenol and fullerenol synthesis by-products prepared in alkaline media. J. Nanopart. Res. 16, 1-15.
Go to original source...
- Injac, R., Perse, M., Boskovic, M., Djordjevic-Milic, V., Djordjevic, A., Hvala, A., 2008a. Cardioprotective effects of fullerenol C60(OH)24on a single dose doxorubicininduced cardiotoxicity in rats with malignant neoplasm. Technol. Cancer. Res. Tt. 7, 15-25.
Go to original source...
Go to PubMed...
- Injac, R., Perse, M., Obermajer, N., Djordjevic-Milic, V., Prijatelj, M., Djordjevic, A., Cerar, A., Strukelj, B.P., 2008b. Potential hepatorotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials 29, 3451-3460.
Go to original source...
Go to PubMed...
- Injac, R., Boskovic, M., Perse, M., Koprivec-Furlan, E., Cerar, A., Djordjevic, A., Strukelj, B., 2008c. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated by fullerenol c60(OH)24 via suppression of oxidative stress. Pharm. Res. 60, 742-749.
Go to original source...
Go to PubMed...
- Injac, R., Perse, M., Obermajer, N., Djordjevic-Milic, V., Prijatelj, M., Djordjevic, A., Cerar, A., Strukelj, B.P., 2009a. Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer. Biomaterilas 30, 1184-1196.
Go to original source...
Go to PubMed...
- Injac, R., Radic, N., Govedarica, B., Perse, M., Cerar, A., Djordjevic, A., Strukelj, B.P., 2009b. Acute doxorubicin pulmotoxicity in rats with malignant neoplasm is effectively treated with fullerenol C60(OH)24 through inhibition of oxidative stress. Pharmacol. Rep. 61, 335-342.
Go to original source...
Go to PubMed...
- Jamalludin, M., Wang, S., Boldogh, I., Tian, B., Braiser, A.R., 2007. TNF-a-induced NFkB/RelA Ser276 phosphorylation and enhance some formation is mediated by an ROS-dependent PKAc pathway. Cell. Signal. 19, 1419-1433.
Go to original source...
Go to PubMed...
- Johnson-Lyles, D.N., Peifley, K., Lockett, S., Neun, B.W., Hansen, M., Clogston, J., Stern, S.T., Mcneil, S.E., 2010. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction. Toxicol. Appl. Pharmacol. 248, 249-258.
Go to original source...
Go to PubMed...
- Koukourakis, M., 2012. Radiation damage and radioprotectants: new concepts in the era of molecular medicine. Brit. J. Radiol. 85, 313-330.
Go to original source...
Go to PubMed...
- Krokosz, A., Grebowski, J., Rodacka, A., Pasternak, B., Puchala, M., 2014. The effect of fullerenol C60(OH)$30 on the alcohol dehydrogenase activity irradiated with Xrays. Radiat. Phys. Chem. 97, 102-106.
Go to original source...
- Kuntic, V.S., Stankovic, M.B., Vujic, Z.B., Brboric, J.S., Uskokovic-Markovic, S.M., 2013. Radioprotectors - the evergreen topic. Chem. Biodivers. 10, 1791-1803.
Go to original source...
Go to PubMed...
- Litchfield, J., Wilcoxon, F., 1949. A simplified method of evaluating dose-effects experiments. J. Pharmacol. Exp. Ther. 96, 99-113.
- Ma, H.L., Liang, X.J., 2010. Fullerenes as unique nanopharmaceuticals for disease treatment. Sci. China-Chem. 53, 2233-2240.
Go to original source...
- Mettler Jr., F.A., Brenner, D., Coleman, C.N., Kaminski, J.M., Kennedy, A.R., Wagner, L. K., 2011. Can radiation risks to patients be reduced without reducing radiation exposure? The status of chemical radioprotectants. AJR Am. J. Roentg. 196, 616- 618.
Go to original source...
Go to PubMed...
- Mihailovic, M., Dobric, S., Poznanovic, G., Petrovic, M., Uskokovic, A., Arambasic, J., Bogojevic, D., 2009. The acute-phase protein a2-macroglobulin plays an important role in radioprotection in the rat. Shock 31, 607-614.
Go to original source...
Go to PubMed...
- Mirkov, S., Djordjevic, A., Andric, N., Andric, S., Kostic, T., Bogdanovic, G., VojinovicMiloradov, M., Kovacevic, R., 2004. Nitric oxide-scavenging activity of polyhydroxylated fullerenol. Nit. Oxide: Biol. Chem. 11, 201-207.
Go to original source...
Go to PubMed...
- Murley, J.S., Kataoka, Y., Weydert, C.J., Oberley, L.W., Grdina, D.J., 2006. Delayed radioprotection by nuclear transcription factor kappa B mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger WR1065. Free Radic. Bio. Med. 40, 1004-1016.
Go to original source...
Go to PubMed...
- Narayanan, K.B., Park, H.H., 2013. Pleiotropic functions of antioxidant nanoparticles for longevity and medicine. Adv. Colloid. Interfac. 201, 30-42.
Go to original source...
Go to PubMed...
- Piper, J.R., Stringfellow Jr., C.R., Eliot, R.D., Johnston, T.P., 1969. S-[2-(.omega.aminoalkylamino)ethyl] dihydrogen phosphorothioates and related compounds as potential antiradiation agents. J. Med. Chem. 12, 236-243.
Go to original source...
Go to PubMed...
- Prasad, K.N., 2005. Rationale for using multiple antioxidants in protecting humans against low doses of ionizing radiation. Br. J. Radiol. 78, 485-492.
Go to original source...
Go to PubMed...
- Quingnuan, L., Yan, X., Xiaodong, Z., Ruili, L., Qieqie, D., Xiaoguang, S., Shaoliang, C., Wenxin, L., 2002. Preparation of 99mTc-C60(OH)x and its biodistribution studies. Nucl. Med. Biol. 29, 707-710.
Go to original source...
Go to PubMed...
- Rades, D., Fehlauer, F., Bajrovic, A., Mahlmann, B., Richter, E., Alberti, W., 2004. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients. Radiother. Oncol. 70, 261-264.
Go to original source...
Go to PubMed...
- Roursgaard, M., Poulsen, S., Kepley, L., Nielsen, G.H., Larsen, S., 2008. Polyhydroxylated C60 fullerene (fullerenol) attenuates neutrophilic lung inflammation in mice. Basic. Clin. Pharmacol. Toxicol. 103, 386-388.
Go to original source...
Go to PubMed...
- Shipelin, V.A., Trushina, E.N., Avreneva, L.I., Soto, S.K., Batishcheva, S.Y., Maltsev, G.Y., Gmoshinski, I.V., Khotimchenko, S.A., Tutelyan, V.A., 2013. Toxicological and sanitary characteristics of fullerenol (hydroxylated fullerene C60) in 28-day in vivo experiment. Nanotech. Russia 8, 799-809.
Go to original source...
- Smoluk, G.D., Fahey, R.C., Calabro-Jones, P.M., Aguilera, J.A., Ward, J.P., 1988. Radioprotection of cells in culture by WR-2721 and derivatives: form of the drug responsible for protection. Cancer. Res. 48, 3641-3647.
Go to PubMed...
- Spencer, C.M., Goa, K.L., 1995. Amifostine. a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs 50, 1001-1031.
Go to original source...
Go to PubMed...
- Stankov, K., Borisev, I., Kojic, V., Rutonjski, L., Bogdanovic, G., Djordjevic, A., 2013. Modification of antioxidative and antiapoptotic genes expression in irradiated K562 cells upon fullerenol C60(OH)24 nanoparticle treatment. J. Nanosci. Nanotechnol. 13, 105-113.
Go to original source...
Go to PubMed...
- Thakral, S., Thakral, N.K., 2013. Potential medical applications of fullerenes: an overview. In: Bagchi, D., Bagchi, M., Moriyama, H., Shahidi, F. (Eds.), BioNanotechnology: A Revolution in Food, Biomedical and Health Sciences. WileyBlackwell, New-York, pp. 424-441.
Go to original source...
- Trajkovic, S., Dobric, S., Djordjevic, A., Dragojevic-Simic, V., Milovanovic, Z., 2005. Radioprotective efficiency of fullerenol in irradiated mice. Mater. Sci. Forum. 494, 549-554.
Go to original source...
- Trajkovic, S., Dobric, S., Jacevic, V., Dragojevic-Simic, V., Milovanovic, Z., Djordjevic, A., 2007. Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloid Surf. B 58, 39-43.
Go to original source...
Go to PubMed...
- Utley, J.F., Marlowe, C., Wadel, W.J., 1980. Distribution of 35S-labeled WR-2721 in normal and malignant tissue of the mouse. Radiat. Res. 40, 1519-1524.
- Vardy, J., Wong, E., Izard, M., Clifford, A., Clarke, S.J., 2002. Life-threatening anaphylactoid reaction of amifostine used in concurrent chemoradiotherapy for nasopharyngeal cancer in a patient with dermatomyositis: a case report with literature review. Anti-Cancer Drug 13, 327-330.
Go to original source...
Go to PubMed...
- Yan, L., Gu, Z., Zhao, Y., 2013. Chemical mechanisms of the toxicological properties of nanomaterials: generation of intracellular reactive oxygen species. Chem-Asian J. 8, 2342-2353.
Go to original source...
Go to PubMed...
- Yang, X., Jin, L., Yao, L., Shen, F.H., Shimer, A.L., Li, X., 2014. Antioxidative nanofullerol prevents intervertebral disk degeneration. Int. J. Nanomed. 9, 2419-2430.
Go to original source...
Go to PubMed...
- Ye, S., Chen, M., Jiang, Y., Chen, M., Zhou, T., Wang, Y., Hou, Y.Q., Ren, L., 2014. Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system. Int. J. Nanomed. 9, 2073-2087.
Go to original source...
Go to PubMed...
- Yuhas, J.M., 1980. Active versus passive absorption kinetics as the basis for selective protection of normal tissues by A-2-(3-aminopropylamino)ethylphosphororhioic acid. Cancer. Res. 40, 1519-1524.
- Zabbarova, I., Kanai, A., 2008. Targeted delivery of radioprotective agents to mitochondria. Mol. Interventions 8, 294-302.
Go to original source...
Go to PubMed...
- Zois, C.E., Giatromanolaki, A., Sivridis, E., Tokmakidis, S.P., Botaitis, S., Simopoulos, C., Kortsaris, A., Koukourakis, M.I., 2011. Narrow amifostine dose windows define radioprotection outcome, following fractionated wholebody irradiation of mice. In Vivo 25, 191-196.
Go to PubMed...
- da Rocha, A.M., Ferreira, J.R., Barros, D.M., Pereira, T.C.B., Bogo, M.R., Oliveira, S., Geraldo, V., Lacerda, R.G., Ferlauto, A.S., Ladeira, L.O., Pinheiro, M.V., Monserrat, J.M., 2013. Gene expression and biochemical responses in brain of zebrafish Daniorerio exposed to organic nanomaterials: carbon nanotubes (SWCNT) and fullerenol (C60(OH)18-22(OK4)). Comp. Biochem. Phys. A 165, 460-467.
Go to original source...
Go to PubMed...