Garcés Mariana, Marchini Timoteo, Cáceres Lourdes, Calabró Valeria, Mebert Andrea M, Tuttolomondo María Victoria, Vico Tamara, Vanasco Virginia, Tesan Fiorella, Salgueiro Jimena, Zubillaga Marcela, Desimone Martín F, Valacchi Giuseppe, Alvarez Silvia, Magnani Natalia D, Evelson Pablo A
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Argentina; Universidad de Buenos Aires, CONICET, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Facultad de Farmacia y Bioquímica, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Química Analítica Instrumental, Argentina; Universidad de Buenos Aires, CONICET, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Argentina.
Toxicology. 2021 Dec;464:153020. doi: 10.1016/j.tox.2021.153020. Epub 2021 Nov 2.
There is an increasing concern over the harmful effects that metallic nanoparticles (NP) may produce on human health. Due to their redox properties, nickel (Ni) and Ni-containing NP are particularly relevant. Hence, the aim of this study was to establish the toxicological mechanisms in the cardiorespiratory oxidative metabolism initiated by an acute exposure to Ni-doped-NP. Mice were intranasally instilled with silica NP containing Ni (II) (Ni-NP) (1 mg Ni (II)/kg body weight) or empty NP as control, and 1 h after exposure lung, plasma, and heart samples were obtained to assess the redox metabolism. Results showed that, NP were mainly retained in the lungs triggering a significantly increased tissue O consumption rate, leading to Ni-NP-increased reactive oxygen species production by NOX activity, and mitochondrial HO production rate. In addition, an oxidant redox status due to an altered antioxidant system showed by lung GSH/GSSG ratio decreased, and SOD activity increased, resulting in an increased phospholipid oxidation. Activation of circulating polymorphonuclear leukocytes, along with GSH/GSSG ratio decreased, and phospholipid oxidation were found in the Ni-NP-group plasma samples. Consequently, in distant organs such as heart, Ni-NP inhalation alters the tissue redox status. Our results showed that the O metabolism analysis is a critical area of study following Ni-NP inhalation. Therefore, this work provides novel data linking the redox metabolisms alterations elicited by exposure to Ni (II) adsorbed to NP and cardiorespiratory toxicity.
人们越来越关注金属纳米颗粒（NP）可能对人类健康产生的有害影响。由于其氧化还原特性，镍（Ni）及含镍NP尤为重要。因此，本研究的目的是确定急性暴露于掺镍NP引发的心肺氧化代谢中的毒理学机制。给小鼠经鼻滴注含镍（II）的二氧化硅NP（Ni-NP）（1毫克镍（II）/千克体重）或作为对照的空NP，暴露1小时后获取肺、血浆和心脏样本以评估氧化还原代谢。结果表明，NP主要滞留在肺中，引发组织氧消耗率显著增加，导致通过NOX活性产生的活性氧增加以及线粒体HO产生率增加。此外，肺中GSH/GSSG比值降低和SOD活性增加表明抗氧化系统改变导致氧化还原状态失衡，进而导致磷脂氧化增加。在Ni-NP组血浆样本中发现循环多形核白细胞活化，同时GSH/GSSG比值降低和磷脂氧化。因此，在心脏等远处器官，吸入Ni-NP会改变组织氧化还原状态。我们的结果表明，氧代谢分析是吸入Ni-NP后一个关键的研究领域。因此，这项工作提供了新的数据，将暴露于吸附在NP上的镍（II）引发的氧化还原代谢改变与心肺毒性联系起来。
