Variability in the Clearance of Lead Oxide Nanoparticles Is Associated with Alteration of Specific Membrane Transporters

Abstract

Lead oxide nanoparticles (PbONPs), upon their entry into the lungs via inhalation, induce structural changes in primary and secondary target organs. The fate and ultrastructural localization of PbONPs in organs is known to be dependent on the specific organ. Here, we focused on the differences in the ability to clear the inhaled PbONPs from secondary target organs and on molecular and cellular mechanisms contributing to nanoparticle removal. Mice were exposed to PbONPs in whole-body inhalation chambers. Clearance of ionic lead and PbONPs (Pb/PbONPs) from the lungs and liver was very effective, with the lead being almost completely eliminated from the lungs and the physiological state of the lung tissue conspicuously restored. Kidneys exposed to nanoparticles did not exhibit serious signs of damage; however, LA-ICP-MS uncovered a certain amount of lead located preferentially in the kidney cortex even after a clearance period. The concentration of lead in femurs, as representatives of the axial skeleton, was the highest among studied organs at all designated time points after PbONP exposure, and the clearance ability of lead from the femurs was very low in contrast to other organs. The organ-specific increase of ABC transporters expression (ABCG2 in lungs and ABCC3 in the liver) was observed in exposed animals, suggesting their involvement in removing Pb/PbONPs from tissues. Moreover, the expression of caveolins and clathrin displayed a tissue-specific response to lead exposure. Our results uncovered high variability among the organs in their ability to clear Pb/PbONPs and in the transporters involved in this process.

A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

“…However, there were no Pb(NO3)2 NPs found in analyzed kidney cortex (Fig. 6B, C) and the lead was present only in the ionic form, which was different from our previously published PbO NPs study, where distinct PbO NPs were identified [18].…”

“…On the other hand, the Na level significantly increased in bones after 2-and 11-week Pb(NO3)2 NP exposure. This finding is in agreement with our previous study [18], which revealed the same trends in bone mineral content changes after inhalation of PbO NPs: Ca, Mg and K concentrations were significantly decreased while Na was increased (not significant). A 5-week clearance period increased the concentrations of Mg (not significant), Ca (p < 0.01) and K (p < 0.001) in the bone relative to the corresponding control animal values.…”

“…The effect of Pb(NO3)2 NP inhalation on femur weight (Fig. S1) was similar to their alteration after exposure to PbO NPs [18]. There was only a small effect (slight reduction) in the Pb level in bones (femurs) after a 5-week clearance period ( Table 2).…”

“…Previous studies have demonstrated an elevated Ca concentration in the kidney after exposure to Pb and/or Cd [51,52]. On the other hand, we previously reported decreased Ca levels after exposure to PbO NP [18]. In the present study, the Ca concentrations in kidneys (Fig.…”

“…In our previous study [18], we evaluated the ability of organs to clear the Pb load of lead oxide nanoparticles (PbO NPs), which are insufficiently soluble and pass the lung barrier to be transported into secondary target organs in the NP form. Here, we instead evaluated tissue response upon exposure of animals to a highly soluble form of Pb, specifically Pb(NO3)2 NPs.…”