In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors / Minigalieva I.A., Katsnelson B.A., Panov V.G., Privalova L.I., Varaksin A.N., Gurvich V.B., Sutunkova M.P., Shur V.Y., Shishkina E.V., Valamina I.E., Zubarev I.V., Makeyev O.H., Meshtcheryakova E.Y., Klinova S.V. // Toxicology. - 2017. - V. 380, l. . - P. 72-93.

ISSN:
0300483X
Type:
Article
Abstract:
Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.t.) (for performing a broncho-alveolar lavage in 24 h to estimate the cytological and biochemical indices of the response of the lower airways), while in the other, Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks (for estimating the accumulation of corresponding metals in the blood and their excretion with urine and feces and for assessing subchronic intoxication by a large number of functional and morphological indices). Mathematical description of the results from both experiments with the help of the Response Surface Methodology has shown that, as well as in the case of any other binary toxic combinations previously investigated by us, the response of the organism to a simultaneous exposure to any two of the Me-NPs under study is characterized by complex interactions between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which effect it is estimated for as well as on the levels of the effect and dose. With any third Me-NP species acting in the background, the type of combined toxicity displayed by the other two may change significantly (as in the earlier described case of a triple combination of soluble metal salts). It is shown that various harmful effects produced by CuO-NP + ZnO-NP + PbO-NP combination may be substantially attenuated by giving rats per os a complex of innocuous bioactive substances theoretically expected to provide a protective integral and/or metal-specific effect during one month before i.t. instillation or during the entire period of i.p. injections. © 2017 Elsevier B.V.
Author keywords:
Bioprotectors; Combined toxicity; Copper oxide; Lead oxide; Nanotoxicology; Zinc oxide
Index keywords:
acetylcysteine; alkaline phosphatase; alpha tocopherol; ascorbic acid; calcium; colecalciferol; copper oxide nanoparticle; cysteine; ferrochelatase; ferrous sulfate; glutamate sodium; glutamic acid; g
DOI:
10.1016/j.tox.2017.02.007
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013350296&doi=10.1016%2fj.tox.2017.02.007&partnerID=40&md5=5cb9c7e63b1d55f253990b7a91520209
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Affiliations The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russian Federation; Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, Ekaterinburg, Russian Federation; School of Natural Sciences and Mathematics, The Ural Federal University, Ekaterinburg, Russian Federation; The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russian Federation
Author Keywords Bioprotectors; Combined toxicity; Copper oxide; Lead oxide; Nanotoxicology; Zinc oxide
Chemicals/CAS acetylcysteine, 616-91-1; alkaline phosphatase, 9001-78-9; alpha tocopherol, 1406-18-4, 1406-70-8, 52225-20-4, 58-95-7, 59-02-9; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; calcium, 7440-70-2, 14092-94-5; colecalciferol, 1406-16-2, 67-97-0; cysteine, 4371-52-2, 52-89-1, 52-90-4; ferrochelatase, 9012-93-5; ferrous sulfate, 10028-21-4, 10124-49-9, 13463-43-9, 7720-78-7, 7782-63-0; glutamate sodium, 142-47-2, 16177-21-2, 16690-92-9; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; glycine, 56-40-6, 6000-43-7, 6000-44-8; iodine, 7553-56-2; lead oxide, 1317-36-8, 1335-25-7, 74891-45-5, 79120-33-5; pectin, 9000-69-5; potassium iodide, 7681-11-0; retinol, 68-26-8, 82445-97-4; selenium, 7782-49-2; copper, 15158-11-9, 7440-50-8; cuprous oxide, 1317-39-1; lead, 7439-92-1, 13966-28-4; oxide, 16833-27-5; zinc oxide, 1314-13-2; Copper; cuprous oxide; Fatty Acids, Omega-3; Lead; lead oxide; Micronutrients; Oxides; pectin; Pectins; Protective Agents; Zinc Oxide
References Abeyemi, O.O., Yemitan, O.K., Taiwo, A.E., Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphianitida nitida AFZEL (2006) Ethnopharmacology, 106, pp. 312-316; Alarifi, S., Ali, D., Verma, A., Alakhtani, S., Ali, B.A., Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells (2013) Int. J. Toxicol., 32, pp. 296-307; Akhtar, M.J., Kumar, S., Alhadlaq, H.A., Alrokayan, S.A., Abu-Salah, K.M., Ahamed, M., Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells (2013) Toxicol. Ind. Health; Asghar, A., Marziyeh, M., Marziyeh, S., Synthesis and toxicity evaluation of lead oxide (PbO) nanoparticles in rats (2016) Electron. J. Biol., 12 (2), pp. 110-114; Box, G.E.P., Draper, N.R., Response Surfaces, Mixtures, and Ridge Analyses (2007), John Wiley & Sons, Inc Hoboken, NJ; Chen, A., Kim, S.S., Chung, E., Dietrich, K.N., Thyroid hormones in relation to lead, mercury, and cadmium exposure in the national health and nutrition examination survey, 2007–2008 (2013) Environ. Health Perspect., 121, pp. 181-186; Choi, J., Kim, H., Kim, P., Jo, E., Kim, H.-M., Lee, M.-Y., Jin, S.M., Park, K., Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration (2015) J. Toxicol. Environ. Health, 78 (4), pp. 226-243; Cornejo-Garrido, H., Kibanova, D., Nieto-Camacho, A., Guzmán, J., Ramírez-Apan, T., Fernández-Lomelín, P., Garduño, M.L., Cervini-Silva, J., Oxidative stress, cytoxicity, and cell mortality induced by nano-sized lead in aqueous suspensions (2011) Chemosphere, 84 (10), pp. 1329-1335; Cuillel, M., Chevallet, M., Charbonnier, P., Fauquant, C., Pignot-Paintrand, I., Arnaud, J., Cassio, D., Mintz, E., Interference of CuO nanoparticles with metal homeostasis in hepatocytes under sub-toxic conditions (2014) Nanoscale, 16, pp. 1707-1715; Euling, S., Gennings, C., Wilson, E.M., Kemppainen, J.A., Kelce, W.R., Kimmel, C.A., Response-surface modeling of the effect of 5α-dihydrotestosterone and androgen receptor levels on the response to the androgen antagonist vinclozin (2002) J. Toxicol. Sci., 69 (2), pp. 332-343; Fernandez, S.P., Wasowski, C., Loscalzo, L.M., Granger, R.E., Johnston, G.A., Paladini, A.C., Marder, M., Central nervous system depressant action of flavonoid glycosides (2006) Eur. J. Pharmacol., 539, pp. 168-176; Filippi, C., Pryde, A., Cowan, P., Lee, T., Hayes, P., Donaldson, K., Plevris, J., Stone, V., Toxicology of ZnO and TiO2 nanoparticles on hepatocytes: impact on metabolism and bioenergetics (2015) Nanotoxicology, 9 (1), pp. 126-134; Fröhlich, E., Salar-Behzadi, S., Toxicological assessment of inhaled nanoparticles: role of in vivo, ex vivo, in vitro, and in silico studies (2014) Int. J. Mol. Sci., 15, pp. 4795-4822; Fröhlich, E., Cellular targets and mechanisms in the cytotoxic action of non-biodegradable engineered nanoparticles (2014) Curr. Drug Metab., 14, pp. 976-988; Gaertner, R.R., Hollebone, B.R., The in vitro inhibition of hepatic ferrochelatase by divalent lead and other soft metal ions (1983) Can. J. Biochem. Cell Biol., 61 (4), pp. 214-222; Geiser, M., Kreyling, W.G., Deposition and biokinetics of inhaled nanoparticles (2010) Part. Fibre Toxicol., 7 (2); Gomes, T., Araújo, O., Pereira, R., Almeida, A.C., Cravo, A., Bebianno, M.J., Genotoxicity of copper oxide and silver nanoparticles in the mussel Mytilus galloprovincialis (2013) Mar. Environ. Res., 84, pp. 51-59; Han, Z., Yan, Q., Ge, W., Liu, Z.G., Gurunathan, S., De Felici, M., Shen, W., Zhang, X.F., Cytotoxic effects of ZnO nanoparticles on mouse testicular cells (2016) Int. J Nanomed., 11, pp. 5187-5203; ICRP, Human respiratory tract model for radiological protection. A report of a Task Group of the International Commission on Radiological Protection (1994) Ann. ICRP, 24, pp. 1-482; Katsnelson, B.A., Degtyareva, T.D., Privalova, L.I., Medvedeva, S., Yu Gurvich, V.B., Denisenko, S.A., Joint sub-chronic fluoro-lead intoxication and weakening of its development by means of a bio protectors complex (2004) Toxicol. Rev., 2, pp. 23-29; Katsnelson, B.A., Makeyev, O.H., Kochneva, N.I., Privalova, L.I., Degtyareva, T.D., Bukhantsev, V.A., Minin, V.V., Kostyukova, S.V., Testing a set of bioprotectors against the genotoxic effect of a combination of ecotoxicants (2007) Cent. Eur. J. Occup. Environ. Med., 13, pp. 251-264; Katsnelson, B.A., Kuzmin, S.V., Degtyareva, T.D., Privalova, L.I., Soloboyeva, J.I., Biological prophylaxis—one of the ways to proceed from the analytical environmental epidemiology to the population health protection (2008) Cent. Eur. J. Occup. Environ. Med., 14, pp. 41-42; Katsnelson, B.A., Privalova, L.I., Kuzmin, S.V., Degtyareva, T.D., Soloboyeva, J.I., Biological prophylaxis as one of the ways to proceed from analytical environmental epidemiology to public health protection (a self-overview) (2008) Eur. Epi-Mark., 12 (3), pp. 1-8; Katsnelson, B.A., Privalova, L.I., Kuzmin, S.V., Degtyareva, T.D., Soloboyeva, J.I., Biological prophylaxis of adverse health effects caused by environmental and occupational impacts – theoretical premises, experimental and field testing, practical realization (2009) Cent. Eur. J. Occup. Environ. Med., 14 (1-2), pp. 35-57; Katsnelson, B.A., Yeremenko, O.S., Privalova, L.I., Makeyev, O.H., Degtyareva, T.D., Beresneva, O.Y., Valamina, I.E., Nazukin, A.S., Toxicity of monazite particulate and its attenuation with a complex of bio-protectors (2009) La Medicina del Lavoro, 100, pp. 455-470; Katsnelson, B.A., Privalova, L.I., Degtyareva, T.D., Sutunkova, M.P., Minigalieva, I.A., Yeremenko, O.S., Kireyeva, E.P., Beikin, J.B., Experimental estimates of the toxicity of iron oxide Fe3O4 (magnetite) nanoparticles (2010) Cent. Eur. J. Occup. Environ. Med., 16, pp. 47-63; Katsnelson, B.A., Privalova, L.I., Kuzmin, S.V., Degtyareva, T.D., Sutunkova, M.P., Yeremenko, O.S., Minigalieva, I.A., Nikolaeva, E.V., Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: are we defenseless against nanoparticles? (2010) Int. J. Occup. Environ. Health, 16, pp. 508-524; Katsnelson, B.A., Degtyareva, T.D., Minigalieva, I.A., Privalova, L.I., Kuzmin, S.V., Yeremenko, O.S., Kireyeva, E.P., Morozova, M.V., Sub-chronic systemic toxicity and bio-accumulation of Fe3O4 nano- and microparticles following repeated intraperitoneal administration to rats (2011) Int. J. Toxicol., 30, pp. 60-67; Katsnelson, B.A., Privalova, L.I., Kuzmin, S.V., Gurvich, V.B., Sutunkova, M.P., Kireyeva, E.P., Minigalieva, I.A., An approach to tentative reference levels setting for nanoparticles in the workroom air based on comparing their toxicity with that of their micrometric counterparts: a case study of iron oxide Fe3O4 (2012) ISRN Nanotechnol., 1, p. 2; Katsnelson, B.A., Privalova, L.I., Sutunkova, M.P., Loginova, N.V., Gurvich, V.B., Shur, V.Y., Beikin, Y.B., Beljayeva, S.V., Uptake of some metallic nanoparticles by, and their impact on pulmonary macrophages in vivo as viewed by optical, atomic force, and transmission electron microscopy (2012) Nanomed. Nanotechnol. J., 3, pp. 1-8; Katsnelson, B.A., Privalova, L.I., Sutunkova, M.P., Tulakina, L.G., Pichugova, S.V., Beykin, J.B., Khodos, M.J., The in vivo interaction between iron oxide Fe3О4 nanoparticles and alveolar macrophages (2012) Bull. Exp. Biol. Med., 152, pp. 627-631; Katsnelson, B.A., Privalova, L.I., Gurvich, V.B., Makeyev, O.H., Shur, V.Y., Beikin, J.B., Sutunkova, M.P., Tulakina, L.G., Comparative in vivo assessment of some adverse bio-effects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver's effects with a complex of innocuous bioprotectors (2013) Int. J. Mol. Sci., 14, pp. 2449-2483; Katsnelson, B.A., Minigalieva, I.A., Privalova, L.I., Sutunkova, M.P., Gurvich, V.B., Shur, V.Y., Shishkina, E.V., Panov, V.G., Lower airways response in rats to a single or combined intratracheal instillation of manganese and nickel nanoparticles and its attenuation with a bio-protective pre-treatment (2014) Toksicol. Vestnik, 6, pp. 8-14; Katsnelson, B.A., Panov, V.G., Minigalieva, I.A., Varaksin, A.N., Privalova, L.I., Slyshkina, T.V., Grebenkina, S.V., Further development of the theory and mathematical description of combined toxicity: an approach to classifying types of action of three-factorial combinations (a case study of manganese-chromium-nickel subchronic intoxication) (2015) Toxicology, 334, pp. 33-44; Katsnelson, B.A., Privalova, L.I., Sutunkova, M.P., Minigalieva, I.A., Gurvich, V.B., Shur, V.Y., Makeyev, O.H., Grigoryeva, E.V., Is it possible to enhance the organism's resistance to toxic effects of metallic nanoparticles? (2015) Toxicology, 337, pp. 79-82; Katsnelson, B.A., Privalova, L.I., Sutunkova, M.P., Minigalieva, I.A., Panov, V.G., Varaksin, A.N., Gurvich, V.B., Makeyev, O.H., Some patterns of metallic nanoparticles’ combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles (2015) Food Chem. Toxicol., 86, pp. 351-364; Katsnelson, B.A., Tsepilov, N.A., Panov, V.G., Sutunkova, M.P., Varaksin, A.N., Gurvich, V.B., Minigalieva, I.A., Meshtcheryakova, E.Y., Applying theoretical premises of binary toxicity mathematical modeling to combined impacts of chemical plus physical agents (A case study of moderate subchronic exposures to fluoride and static magnetic field) (2016) Food Chem. Toxicol., 95, pp. 110-120; Kolanjiyil, A.V., Deposited nanomaterial mass transfer from lung airways to systemic regions (2013) A Thesis for MSc Degree, , North Cariolina State University Raleigh, NC; Kreyling, W.G., Geiser, M., Dosimetry of inhaled nanoparticles (2009) Nanoparticles in Medicine and Environment, Inhalation and Health Effects, pp. 145-173. , J.C.M. Marijnissen L. Gradon Springer Science & Business Media Dordrecht; Lasagna-Reeves, C., Gonzalez-Romero, D., Barria, M.A., Olmedo, I., Clos, A., Sadagopa Ramanujam, V.M., Urayama, A., Soto, C., Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice (2010) Biochem. Biophys. Res. Commun., 393, pp. 649-655; Magaye, R., Zhao, J., Bowman, L., Ding, M., Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles (2012) Exp. Ther. Med., 4, pp. 551-561; Maulderly, J.L., McCunney, R.G., Particle overload in the rat lung and lung cancer (1997) Implications for Human Risk Assessment, , Taylor & Francis Philadelphia, USA; Minigalieva, I.A., Katsnelson, B.A., Privalova, L.I., Gurvich, V.B., Panov, V.G., Varaksin, A.N., Makeyev, O.H., Grebenkina, S.V., Toxicodynamic and toxicokinetic descriptors of combined chromium(VI) and nickel toxicity (2014) Int. J. Toxicol., 33 (6), pp. 498-505; Minigalieva, I.A., Katsnelson, B.A., Privalova, L.I., Sutunkova, M.P., Gurvich, V.B., Shur, V.Y., Shishkina, E.V., Meshtcheryakova, E.Y., Attenuation of combined nickel (II) oxide and manganese (II, III) oxide nanoparticles’ adverse effects with a complex of bioprotectors (2015) Int. J. Mol. Sci., 16 (9), pp. 22555-22583; Morosova, K.I., Aronova, G.V., Katsnelson, B.A., Velichkovski, B.T., Genkin, A.M., Elnichnykh, L.N., Privalova, L.I., On the defensive action of glutamate on the cytotoxicity and fibrogenicity of quartz dust (1982) Br. J. Ind. Med., 39, pp. 244-252; Morosova, K.I., Katsnelson, B.A., Rotenberg YuS. Belobragina, G.V., A further experimental study of the antisilicotic effect of glutamate (1984) Br. J. Ind. Med., 41 (4), pp. 518-525; Myers, R.H., Montgomery, D.C., Anderson-Cook, C.M., Response Surface Methodology. Process and Product Optimization Using Designed Experiments (2009), 3rd ed. John Wiley & Sons New York; Oszlanczi, G., Papp, A., Szabo, A., Nagymajtenyi, L., Sapi, A., Konya, Z., Paulik, E., Vezer, T., Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways (2011) Inhal. Toxicol., 23 (4), pp. 173-181; Panov, V.G., Varaksin, A.N., Identification of combined action types in experiments with two toxicants: a response surface linear model with a cross term (2016) Toxicol. Mechan. Methods, 26 (2), pp. 139-150; Panov, V.G., Katsnelson, B.A., Varaksin, A.N., Privalova, L.I., Kireyeva, E.P., Valamina, I.E., Beresneva Yu, O., Further development of mathematical description for combined (a case study of lead-fluoride combination) (2015) Toxicol. Rep., 2, pp. 297-307; Privalova, L.I., Katsnelson, B.A., Sutunkova, M.P., Valamina, I.E., Beresneva, O.Y., Degtyareva, T.D., Yeremenko, O.S., Attenuation of some adverse health effects of chrysotile asbestos with a bioprotective complex in animal experiments (2007) Cent. Eur. J. Occup. Environ. Med., 13, pp. 265-276; Privalova, L.I., Katsnelson, B.A., Loginova, N.V., Gurvich, V.B., Shur, V.Y., Beikin, Y.B., Sutunkova, M.P., Beljayeva, S.V., Some characteristics of free cell population in the airways of rats after intratracheal instillation of copper-containing nano-scale particles (2014) Int. J. Mol. Sci., 15, pp. 21538-21553; Privalova, L.I., Katsnelson, B.A., Loginova, N.V., Gurvich, V.B., Shur, V.Y., Valamina, I.E., Makeyev, O.H., Kostykova, S.V., Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors (2014) Int. J. Mol. Sci., 15, pp. 12379-12406; Privalova, L.I., Katsnelson, B.A., Varaksin, A.N., Panov, V.G., Balesin, S.L., The pulmonary phagocytosis response to separate and combined impacts of manganese (IV) and chromium (VI) containing particulates (2016) Toxicology, 370, pp. 78-85; Ramachandran, G., Assessing Nanoparticle Risk to Human Health (2016), Elsevier Amsterdam; Rylova, M.L., Methods of Investigating Long-Term Effects of Noxious Environmental Agents in Animal Experiments (1964), Meditsina, Leningrad; Sadauskas, E., Wallin, H., Stolenberg, M., Vogel, U., Doering, P., Larsen, A., Danscher, G., Kupffer cells are central in the removal of nanoparticles from the organism (2007) Part. Fibre Toxicol., 4, pp. 10-16; Studer, A.M., Limbach, L.K., van Duc, L., Krumeich, F., Athanassiou, E.K., Gerber, L.C., Moch, H., Stark, W.J., Nanoparticle cytotoxicity depends on intracellular solubility: comparison of stabilized copper metal and degradable copper oxide nanoparticles (2010) Toxicol. Lett., 1, pp. 169-174; Suhnel, J., Assessment of interaction of biologically active agents by means of the isobole approach: fundamental assumptions and recent developments (1992) Arch. Complex Environ. Stud., 4, p. 35; Sutunkova, M.P., Katsnelson, B.A., Privalova, L.I., Gurvich, V.B., Konysheva, L.K., Shur, V.Y., Shishkina, Zubarev, S.V., IV, On the contribution of the phagocytosis and the solubilization to the iron oxide nanoparticles retention in and elimination from lungs under long-term inhalation exposure (2016) Toxicology, 363, pp. 19-28; Swift, D.L., Johannsen, N.M., Earnest, C.P., Blair, S.N., Church, T.S., The effect of different doses of aerobic exercise training on total bilirubin levels (2012) Med. Sci. Sports Exercise, 44 (4), pp. 569-574; Tallarida, R.J., Drug synergism: its detection and applications (2001) J. Pharmacol. Exp. Ther., 298 (3), pp. 865-872; Tong, T., Wilke, C.M., Wu, J., Binh, C.T., Kelly, J.J., Gaillard, J.F., Gray, K.A., Combined toxicity of nano-zno and nano-tio2: from single- to multinanomaterial systems (2015) Environ. Sci. Technol., 49 (13), pp. 8113-8123; Utembe, W., Potgieter, K., Stefaniak, A.B., Gulumian, M., Dissolution and biodurability: important parameters needed for risk assessment of nanomaterials (2015) Part. Fibre Toxicol., 12 (11); Varaksin, A.N., Katsnelson, B.A., Panov, V.G., Privalova, L.I., Kireyeva, E.P., Valamina, I.E., Beresneva, Y.O., Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead (2014) Food Chem. Toxicol., 64, pp. 144-156; Wei, Y., Li, Y., Jia, J., Jiang, Y., Zhao, B., Zhang, Q., Yan, B., Aggravated hepatotoxicity occurs in aged mice but not in young mice after oral exposure to zinc oxide nanoparticles (2016) Nanoimpact, 3-4, pp. 1-11; Xu, J., Li, Z., Xu, P., Xiao, L., Yang, Z., Nanosized copper oxide induces apoptosis through oxidative stress in podocytes (2013) Arch. Toxicol., 87, pp. 1067-1073
Correspondence Address Katsnelson, B.A.30 Popov Str, Russian Federation; email: bkaznelson@etel.ru
Publisher Elsevier Ireland Ltd
CODEN TXCYA
PubMed ID 28212817
Language of Original Document English
Abbreviated Source Title Toxicology
Source Scopus