Disruption of pulmonary resolution mediators contribute to exacerbated silver nanoparticle-induced acute inflammation in a metabolic syndrome mouse model

Alqahtani, Saeed; Xia, Li; Jannasch, Amber; Ferreira, Christina R.; Franco, Jackeline; Shannahan, Jonathan H.

doi:10.1016/j.taap.2021.115730

Cited by 10 publications

(41 citation statements)

References 79 publications

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“…This is a well-established model for producing mice with metabolic syndrome (MetS) [27,28]. Our previous work has generated consistent results with very little variability in inducing MetS by using these diets [19][20][21]. Specifically, we have established these diets result in approximately a 50% weight gain and over a 30% increase in total cholesterol levels and 6% in insulin without altering hemoglobin A1C [19,21].…”

Section: Animal Modelmentioning

confidence: 68%

“…Original NPs and those with the BCs were diluted to a concentration of 25 µg/mL and characterized via assessment of hydrodynamic size, polydispersity index, and ζ-potential (ZetaSizer Nano, Malvern Panalytical Ltd., Malvern, UK) (n = 3/particle). These methods have been previously utilized by our laboratory and other to characterize and verify NPs and NP-BCs [19][20][21][22]29,30].…”

Section: Np-bc Formation and Characterizationmentioning

confidence: 99%

“…Untreated cells were used as controls for XRF analyzer measurements. To qualitatively examine NP-cell associations, Cytoviva enhanced hyperspectral dark field microscopy was utilized [20,40]. Briefly, following exposure to SFM (controls) or 25 µg/mL NPs with BCs for 24 h, macrophages were stained with DAPI to identify the nucleus through fluorescent imaging.…”

Section: Macrophage Association Of Npsmentioning

confidence: 99%

“…For example, individuals with MetS exposed to World Trade Center dust exhibited diminished lung function compared to healthy individuals [18]. Our recent research has demonstrated enhanced susceptibility to inflammation in a MetS mouse model compared to a healthy following pulmonary exposure to silver nanoparticles [19,20]. Although, susceptibility is recognized, the mechanisms are unknown by which underlying disease states such as MetS enhance toxicity following inhalation exposures.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous diseases alter the biological milieu which may influence BC formation and contribute to susceptibility differences. Our previous research demonstrated unique BCs form in obese human serum compared to healthy resulting in altered cellular interactions and immune responses [19][20][21][22]. MetS modifies the biomolecule content within the circulation and also extend to changes in the lung.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Pulmonary Toxicity in Metabolic Syndrome Due to Variations in Iron Oxide Nanoparticle-Biocorona Composition

et al. 2022

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Nanoparticles (NPs) interact with biomolecules by forming a biocorona (BC) on their surface after introduction into the body and alter cell interactions and toxicity. Metabolic syndrome (MetS) is a prevalent condition and enhances susceptibility to inhaled exposures. We hypothesize that distinct NP-biomolecule interactions occur in the lungs due to MetS resulting in the formation of unique NP-BCs contributing to enhanced toxicity. Bronchoalveolar lavage fluid (BALF) was collected from healthy and MetS mouse models and used to evaluate variations in the BC formation on 20 nm iron oxide (Fe3O4) NPs. Fe3O4 NPs without or with BCs were characterized for hydrodynamic size and zeta potential. Unique and differentially associated proteins and lipids with the Fe3O4 NPs were identified through proteomic and lipidomic analyses to evaluate BC alterations based on disease state. A mouse macrophage cell line was utilized to examine alterations in cell interactions and toxicity due to BCs. Exposures to 6.25, 12.5, 25, and 50 μg/mL of Fe3O4 NPs with BCs for 1 h or 24 h did not demonstrate overt cytotoxicity. Macrophages increasingly associated Fe3O4 NPs following addition of the MetS BC compared to the healthy BC. Macrophages exposed to Fe3O4 NPs with a MetS-BC for 1 h or 24 h at a concentration of 25 μg/mL demonstrated enhanced gene expression of inflammatory markers: CCL2, IL-6, and TNF-α compared to Fe3O4 NPs with a healthy BC. Western blot analysis revealed activation of STAT3, NF-κB, and ERK pathways due to the MetS-BC. Specifically, the Jak/Stat pathway was the most upregulated inflammatory pathway following exposure to NPs with a MetS BC. Overall, our study suggests the formation of distinct BCs due to NP exposure in MetS, which may contribute to exacerbated inflammatory effects and susceptibility.

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