title: Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors.
abstract: In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles<100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism's resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20±10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a "bio-protective complex" (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism's status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified.
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. privalovali@yahoo.com.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Privalova
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. bkaznelson@etel.ru.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Katsnelson
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. tushkanN@yandex.ru.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Loginova
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. Gurvich@ymrc.ru.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Gurvich
authors.affiliation: The Institute of Natural Sciences, the Ural Federal University, Ekaterinburg 630000, Russia. vladimir.shur@usu.ru.
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Shur
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. ivalamina@mail.ru.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Valamina
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. ommt305@mail.ru.
authors.forename: Oleg H
authors.initials: OH
authors.lastname: Makeyev
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. marinasutunkova@yandex.ru.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Sutunkova
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. minigalieva@yandex.ru.
authors.forename: Ilzira A
authors.initials: IA
authors.lastname: Minigalieva
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. katerinakir@yandex.ru.
authors.forename: Ekaterina P
authors.initials: EP
authors.lastname: Kireyeva
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 630014, Russia. honored_sci@yahoo.com.
authors.forename: Vadim O
authors.initials: VO
authors.lastname: Rusakov
authors.affiliation: The Institute of Natural Sciences, the Ural Federal University, Ekaterinburg 630000, Russia. anastasiya.tyurnina@labfer.usu.ru.
authors.forename: Anastasia E
authors.initials: AE
authors.lastname: Tyurnina
authors.affiliation: The Institute of Natural Sciences, the Ural Federal University, Ekaterinburg 630000, Russia. roman.kozin@labfer.usu.ru.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Kozin
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. katusha-ugma@rambler.ru.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Meshtcheryakova
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. akorotkov64@mail.ru.
authors.forename: Artem V
authors.initials: AV
authors.lastname: Korotkov
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. eshuman@gmail.com.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Shuman
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. dor_3110@mail.ru.
authors.forename: Anastasia E
authors.initials: AE
authors.lastname: Zvereva
authors.affiliation: Central Research Laboratory, the Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 630109, Russia. svkostyukova@mail.ru.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kostykova
mesh_terms: D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics / Q000633:toxicity*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D003300:Copper / Q000493:pharmacokinetics / Q000633:toxicity*; D004249:DNA Damage; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D000075322:Heavy Metal Poisoning; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity; D010368:Pectins / Q000494:pharmacology*; D011041:Poisoning / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D014018:Tissue Distribution; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D000395:Air Pollutants, Occupational; D000596:Amino Acids; D015525:Fatty Acids, Omega-3; D020011:Protective Agents; D014815:Vitamins; D003300:Copper; D010368:Pectins; C030973:cupric oxide