Inflammatory cytokine concentrations in A) BAL fluid and B) blood plasma.

<p>(†P < 0.05 compared to the vehicle control and WC-Co NP exposed groups)</p

Histology of isolated BAL fluid cells from a representative A) control (vehicle only) rat and B) 500 μg WC-Co NP exposed rat.

<p>Scale bars = 20 μm. (black arrow = alveolar macrophage, AM; arrow head = erythrocyte; dotted arrow = polymorphonuclear leukocyte, PMN; wide arrow = AM with WC-Co NPs)</p

Pulmonary inflammation parameters assessed in the BAL fluid following 24-hr exposure to WC-Co and CeO₂ NPs: A) LDH activity, B) albumin, and C) AM chemiluminescence.

<p>Values presented as mean ± SD. (*P < 0.05, ‡P < 0.001 compared to the vehicle control, and †P < 0.01 compared to WC-Co NP exposed groups)</p

Summary of the characteristics of WC-Co NP, including size and elemental composition.

<p>Summary of the characteristics of WC-Co NP, including size and elemental composition.</p

Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO₂ nanoparticle exposure

<div><p></p><p>Due to the ongoing evolution of nanotechnology, there is a growing need to assess the toxicological outcomes in under-studied populations in order to properly consider the potential of engineered nanomaterials (ENM) and fully enhance their safety. Recently, we and others have explored the vascular consequences associated with gestational nanomaterial exposure, reporting microvascular dysfunction within the uterine circulation of pregnant dams and the tail artery of fetal pups. It has been proposed (<i>via</i> work derived by the Barker Hypothesis) that mitochondrial dysfunction and subsequent oxidative stress mechanisms as a possible link between a hostile gestational environment and adult disease. Therefore, in this study, we exposed pregnant Sprague-Dawley rats to nanosized titanium dioxide aerosols after implantation (gestational day 6). Pups were delivered, and the progeny grew into adulthood. Microvascular reactivity, mitochondrial respiration and hydrogen peroxide production of the coronary and uterine circulations of the female offspring were evaluated. While there were no significant differences within the maternal or litter characteristics, endothelium-dependent dilation and active mechanotransduction in both coronary and uterine arterioles were significantly impaired. In addition, there was a significant reduction in maximal mitochondrial respiration (state 3) in the left ventricle and uterus. These studies demonstrate microvascular dysfunction and coincide with mitochondrial inefficiencies in both the cardiac and uterine tissues, which may represent initial evidence that prenatal ENM exposure produces microvascular impairments that persist throughout multiple developmental stages.</p></div

Elevated concentrations of Cd and Cr in the liver 1, 3, and 7 days after a single exposure.

<p>Levels of Cd (A) and Cr (B) were determined via ICP-MS. Both Cd and Cr accumulated in a dose-dependent manner at 24 h. Cd levels remained elevated for all doses on days 3 and 7 post-exposure. Cr levels rapidly declined between days 1 and 3, and this trend continued at the low and medium doses, but in the high dose remained at day 3 levels on day 7. Values are mean ±SE, n = 5–7 animals per group.</p

Cr, but not Cd exposure induced DNA damage in rat liver.

<p>A comet assay was performed to assess DNA strand breaks in hepatocytes from Cd (A) or Cr (B) treated animals. Cd exposure had no effect on Comet tail length. However, Cr induced DNA strand breaks at the medium and high doses, and this was sustained at all days examined. Data are expressed as mean ±SE, n = 2–7 animals per group. ^†Only two comet assays were available for analysis on days 1 and 3. *Significantly different from control on each day, p<0.05.</p

Altered H₂O₂ levels in the liver occur well after Cd or Cr exposure.

<p>H_<b>2</b>O_<b>2</b> concentrations were monitored via a colorimetric assay. All three doses of Cd (A) increased H_<b>2</b>O_<b>2</b> concentrations on day 7 in a dose-dependent manner. Only the high dose of Cr (B) led to increased H_<b>2</b>O_<b>2</b> concentrations on days 3 and 7. Values are mean ±SE, n = 6–7 animals per group. *Significantly different from control on each day, <i>p</i><0.05. ^†<i>p</i> = 0.053.</p

Delayed induction of free radicals in the liver after Cd and Cr exposure.

<p>Liver tissue slices from Cd (A and C) and Cr (B and D) exposed animals were incubated with hydroxy-TEMPO with or without the •OH scavenger DMTU, and examined via ESR. Total free radical levels dose-dependently increased for both metal exposures 1, 3 and 7 days post-injection (A and B). An indication of the contribution of •OH to total ROS was determined by examining the differences in ESR peak height after the addition of DTMU (C and D). Cr exposure dose-dependently increased •OH production at the mid and high doses on days 3 and 7. Values are mean ±SE, n = 6–7 animals per group. *Significantly different from control on each day, <i>p</i><0.05. ^†Significantly different from other days in the same dose.</p

Differentially expressed probe sets and persistent changes in expression following Cd or Cr exposure in the liver.

<p>Venn diagrams of (A) total probe sets from all time points for each metal and (B) probe sets on each day included for enrichment analysis. Probe sets were considered significant with a fold-change ≥ 1.8 or ≤ -1.8 and either an FDR < 0.05 (day 1) or unadjusted <i>p</i>-value < 0.05 (days 3 and 7).</p