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. 2023 Mar 15;2(5):740-748.
doi: 10.1039/d2va00300g. eCollection 2023 May 9.

Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiO2 nanoparticle inhalation exposure

Todd R Harris  1 , Julie A Griffith  2   3 , Colleen E C Clarke  1 , Krista L Garner  2   3 , Elizabeth C Bowdridge  2   3 , Evan DeVallance  2   3 , Kevin J Engles  2 , Thomas P Batchelor  2   3 , William T Goldsmith  2   3 , Kim Wix  2 , Timothy R Nurkiewicz  2   3 , Amy A Rand  1
Affiliations

Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiO2 nanoparticle inhalation exposure

Todd R Harris et al. Env Sci Adv. .

Abstract

Nano-titanium dioxide (nano-TiO2) is a widely used nanomaterial found in several industrial and consumer products, including surface coatings, paints, sunscreens and cosmetics, among others. Studies have linked gestational exposure to nano-TiO2 with negative maternal and fetal health outcomes. For example, maternal pulmonary exposure to nano-TiO2 during gestation has been associated not only with maternal, but also fetal microvascular dysfunction in a rat model. One mediator of this altered vascular reactivity and inflammation is oxylipid signaling. Oxylipids are formed from dietary lipids through several enzyme-controlled pathways as well as through oxidation by reactive oxygen species. Oxylipids have been linked to control of vascular tone, inflammation, pain and other physiological and disease processes. In this study, we use a sensitive UPLC-MS/MS based analysis to probe the global oxylipid response in liver, lung, and placenta of pregnant rats exposed to nano-TiO2 aerosols. Each organ presented distinct patterns in oxylipid signaling, as assessed by principal component and hierarchical clustering heatmap analysis. In general, pro-inflammatory mediators, such as 5-hydroxyeicosatetraenoic acid (1.6 fold change) were elevated in the liver, while in the lung, anti-inflammatory and pro-resolving mediators such as 17-hydroxy docosahexaenoic acid (1.4 fold change) were elevated. In the placenta the levels of oxylipid mediators were generally decreased, both inflammatory (e.g. PGE2, 0.52 fold change) and anti-inflammatory (e.g. Leukotriene B4, 0.49 fold change). This study, the first to quantitate the levels of these oxylipids simultaneously after nano-TiO2 exposure, shows the complex interplay of pro- and anti-inflammatory mediators from multiple lipid classes and highlights the limitations of monitoring the levels of oxylipid mediators in isolation.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Overview of oxylipid formation from their PUFA precursors.
Fig. 2
Fig. 2. Analysis shows altered lipidome in air vs. nano-TiO2 liver tissue. (A) Principal component analysis. (B) Box plots of significantly altered oxylipids. (C) Heat map visualization of the top 25 discriminating features between air and nano-TiO2 treatments. For panel B, the boundary of the box indicates the 25th and 75th percentile. The horizontal line in the box in the median value, and the whiskers are the 10th and 90th percentiles. The dashed horizontal blue line is the mean value (all outliers represented by filled circles). N = 6 for air group, N = 7 for nano-TiO2 group. Oxylipid concentrations are reported in Table S4.
Fig. 3
Fig. 3. Analysis shows altered lipidome in air vs. nano-TiO2 placental tissue. (A) Principal component analysis. (B) Box plots of significantly altered oxylipids. (C) Heat map visualization of the top 25 discriminating features between air and nano-TiO2 treatments. For panel B, the boundary of the box indicates the 25th and 75th percentile. The horizontal line in the box in the median value, and the whiskers are the 10th and 90th percentiles. The dashed horizontal blue line is the mean value (all outliers represented by filled circles). N = 9 for Air group, N = 10 for nano-TiO2 group. Oxylipid concentrations are reported in Table S6.
Fig. 4
Fig. 4. Analysis shows altered lipidome in air vs. nano-TiO2 lung tissue. (A) Principal component analysis. (B) Box plots of significantly altered oxylipids. (C) Heat map visualization of the top 25 discriminating features between air and nano-TiO2 treatments. For panel B, the boundary of the box indicates the 25th and 75th percentile. The horizontal line in the box in the median value, and the whiskers are the 10th and 90th percentiles. The dashed horizontal blue line is the mean value (all outliers represented by filled circles). N = 9 for air group, N = 10 for nano-TiO2 group. Oxylipid concentrations are reported in Table S5.
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