title: 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.
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 24h 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.
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Ilzira A
authors.initials: IA
authors.lastname: Minigalieva
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia. Electronic address: bkaznelson@etel.ru.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Katsnelson
authors.affiliation: Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, Ekaterinburg, Russia.
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Panov
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Privalova
authors.affiliation: Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, Ekaterinburg, Russia.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Varaksin
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Gurvich
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Sutunkova
authors.affiliation: School of Natural Sciences and Mathematics, The Ural Federal University, Ekaterinburg, Russia.
authors.forename: Vladimir Ya
authors.initials: VY
authors.lastname: Shur
authors.affiliation: School of Natural Sciences and Mathematics, The Ural Federal University, Ekaterinburg, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shishkina
authors.affiliation: The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russia.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Valamina
authors.affiliation: School of Natural Sciences and Mathematics, The Ural Federal University, Ekaterinburg, Russia.
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Zubarev
authors.affiliation: The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russia.
authors.forename: Oleg H
authors.initials: OH
authors.lastname: Makeyev
authors.affiliation: The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russia.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Meshtcheryakova
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Klinova
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003300:Copper / Q000633:toxicity*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007854:Lead / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018977:Micronutrients / Q000494:pharmacology; D008962:Models, Theoretical; D015999:Multivariate Analysis; D010087:Oxides / Q000633:toxicity*; D010316:Particle Size; D010368:Pectins / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D059550:Toxicity Tests, Subchronic; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D015525:Fatty Acids, Omega-3; D018977:Micronutrients; D010087:Oxides; D020011:Protective Agents; D007854:Lead; C047365:lead oxide; D003300:Copper; D010368:Pectins; D015034:Zinc Oxide; C000520:cuprous oxide
keywords: Bioprotectors; Combined toxicity; Copper oxide; Lead oxide; Nanotoxicology; Zinc oxide