title: Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles' Adverse Effects with a Complex of Bioprotectors.
abstract: Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7±8.2 and 18.4±5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected intraperitoneally (IP) to rats at a dose of 2.5 mg/kg 3 times a week up to 18 injections, either alone or in combination. A group of rats was injected with this combination with the background oral administration of a "bio-protective complex" (BPC) comprising pectin, vitamins A, C, E, glutamate, glycine, N-acetylcysteine, selenium, iodide and omega-3 PUFA, this composition having been chosen based on mechanistic considerations and previous experience. After the termination of injections, many functional and biochemical indices and histopathological features (with morphometric assessment) of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The Ni and Mn content of these organs was measured with the help of the atomic emission and electron paramagnetic resonance spectroscopies. We obtained blood leukocytes for performing the RAPD (Random Amplified Polymorphic DNA) test. Although both metallic NPs proved adversely bio-active in many respects considered in this study, Mn₃O₄-NPs were somewhat more noxious than NiO-NPs as concerns most of the non-specific toxicity manifestations and they induced more marked damage to neurons in the striatum and the hippocampus, which may be considered an experimental correlate of the manganese-induced Parkinsonism. The comparative solubility of the Mn₃O₄-NPs and NiO-NPs in a biological medium is discussed as one of the factors underlying the difference in their toxicokinetics and toxicities. The BPC has attenuated both the organ-systemic toxicity and the genotoxicity of Mn₃O₄-NPs in combination with NiO-NPs.
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 620014, Russia. ilzira-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 620014, 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 620014, 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 620014, 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 620014, 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 620000, Russia. vladimir.shur@urfu.ru.
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Shur
authors.affiliation: The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg 620000, Russia. ekaterina.shishkina@labfer.usu.ru.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shishkina
authors.affiliation: The Central Research Laboratory, The Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 620109, Russia. ivalamina@mail.ru.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Valamina
authors.affiliation: The Central Research Laboratory, The Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 620109, Russia. ommt305@mail.ru.
authors.forename: Oleg H
authors.initials: OH
authors.lastname: Makeyev
authors.affiliation: Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, 20 Sofia Kovalevskaya Str., Ekaterinburg 620990, Russia. vpanov@ecko.uran.ru.
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Panov
authors.affiliation: Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, 20 Sofia Kovalevskaya Str., Ekaterinburg 620990, Russia. varaksin@ecko.uran.ru.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Varaksin
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 620014, Russia. grigorieva@ymrc.ru.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Grigoryeva
authors.affiliation: The Central Research Laboratory, The Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 620109, Russia. katusha-ugma@rambler.ru.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Meshtcheryakova
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007454:Iodides / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D017895:Manganese Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D009532:Nickel / Q000008:administration & dosage / Q000009:adverse effects*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects*; D010368:Pectins / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D012643:Selenium / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D014815:Vitamins / Q000494:pharmacology
chemical_list: D015525:Fatty Acids, Omega-3; D007454:Iodides; D017895:Manganese Compounds; D010087:Oxides; D020011:Protective Agents; D014815:Vitamins; C027424:manganese oxide; D009532:Nickel; D010368:Pectins; C028007:nickel monoxide; D012643:Selenium; D005998:Glycine; D000111:Acetylcysteine
keywords: bioprotectors; manganese(II, III) oxide; nanoparticles; nickel(II) oxide; subchronic toxicity