Experimental Research into Metallic and Metal Oxide Nanoparticle Toxicity In Vivo

Abstract

We studied purposefully produced silver, gold, iron oxide, copper oxide, nickel oxide, manganese oxide, lead oxide, and zinc oxide nanoparticles using two experimental models: (a) a single intratracheal (IT) instillation in low doses 24 h before the bronchoalveolar lavage to obtain a fluid for cytological and biochemical assessment; (b) repeated intraperitoneal (IP) injections during 6-7 weeks in non-lethal doses to assess the thus induced subchronic intoxication by a lot of functional and morphological indices and by the distribution and elimination of respective nanoparticles. Along with assessing the toxicity of these metallic nanoparticles (Me-NPs) acting separately, we also studied the same effects of some practically relevant Me-NP combinations. Besides, we carried out a 10-month inhalation experiment with an iron oxide (Fe2O3) nano-aerosol. We demonstrated that Me-NPs are much more noxious as compared with their fine micrometric counterparts although physiological mechanisms of their elimination from lungs proved highly active. At the same time, the in situ cytotoxicity, organ-systemic toxicity and in vivo genotoxicity of Me-NPs having a given geometry strongly depends on their chemical nature as well as on the specific mechanisms of action characteristic of a given metal. Even though being water-insoluble, Me-NPs are significantly solubilized in some biological milieus, and this process plays an important part in their biokinetics in vivo. In toto, Me-NPs are one of the most dangerous occupational and environmental hazards due to their cytotoxicity and genotoxicity, and therefore standards or recommended values of presumably safe Me-NP concentrations in the workplace and ambient air should be significantly lower as compared with those established for their micrometric counterparts. At the same time, the toxicity and even genotoxicity of Me-NPs can be significantly attenuated by background or preliminary administration of adequately composed combinations of some bioactive agents in innocuous doses.