Minigalieva Ilzira A, Katsnelson Boris A, Panov Vladimir G, Privalova Larisa I, Varaksin Anatoly N, Gurvich Vladimir B, Sutunkova Marina P, Shur Vladimir Ya, Shishkina Ekaterina V, Valamina Irene E, Zubarev Ilya V, Makeyev Oleg H, Meshtcheryakova Ekaterina Y, Klinova Svetlana V
The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
Toxicology. 2017 Apr 1;380:72-93. doi: 10.1016/j.tox.2017.02.007. Epub 2017 Feb 15.
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.
通过在去离子水层下对99.99%的纯铜、锌或铅进行激光烧蚀获得的金属氧化物纳米颗粒（Me-NPs）稳定悬浮液，分别以三种二元组合和一种三元组合的形式，在对大鼠进行的两个独立实验中使用。在其中一个实验中，对大鼠进行气管内（i.t.）滴注Me-NPs（以便在24小时后进行支气管肺泡灌洗，以评估下呼吸道反应的细胞学和生化指标），而在另一个实验中，在6周内对大鼠进行18次腹腔内（i.p.）重复注射Me-NPs（用于评估相应金属在血液中的积累及其通过尿液和粪便的排泄情况，并通过大量功能和形态学指标评估亚慢性中毒情况）。借助响应面法对两个实验结果进行的数学描述表明，与我们之前研究的任何其他二元毒性组合情况一样，生物体对同时暴露于所研究的任何两种Me-NPs的反应，取决于所评估的效应类型以及效应水平和剂量，其特征在于所有可能类型的联合毒性（单向作用的相加性、亚相加性或超相加性以及相反效应的不同变体）之间的复杂相互作用。当有任何第三种Me-NP物种存在时，另外两种所表现出的联合毒性类型可能会发生显著变化（如之前所述的可溶性金属盐三元组合的情况）。结果表明，如果在气管内滴注前一个月或在腹腔注射的整个期间，给大鼠口服一种理论上预期能提供整体保护和/或金属特异性作用的无害生物活性物质复合物，那么由CuO-NP+ZnO-NP+PbO-NP组合产生的各种有害效应可能会大幅减弱。
