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Effect of nanoparticle exposure in a living system: probed by quantification of Fetuin-B in plasma proteome and kidney tissue imaging using MALDI imaging mass spectrometry in a rat model

JOURNAL OF NANOPARTICLE RESEARCH(2021)

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Abstract
Nanoparticles have gained importance in various biomedical field viz cosmetics, diagnostics, therapeutics, and food additives. Due to small size, NPs penetrate tissues and cells, thereby interacting with biomolecules such as proteins and nucleic acids. This raises the major concern to investigate the effect of NPs in a living system. Previously, we reported downregulation of Fetuin-B in rat plasma, with the increasing dose level of NP-Fe 4 (P 2 O 7 ) 3 , in rats treated with NP-Fe 4 (P 2 O 7 ) 3 as a food-fortificant. In the present study, we validated the dose response of Fetuin-B in rats exposed to NP-Fe 4 (P 2 O 7 ) 3 , NP-ZnO, and NP-SiO 2 . Fetuin-B showed similar dose responses in all the groups irrespective of their physicochemical properties. Previously, we hypothesized that the immune response was triggered upon exposure to NP-Fe 4 (P 2 O 7 ) 3 in vivo, which led to the differential regulation of Fetuin-B. To evaluate the hypothesis, immunological response was assessed in rats by estimating the pro-inflammatory cytokines in plasma. We observed Interleukin-1α and Interleukin-1β increased with the increasing dose levels of the three NPs. The impact of NPs on the proteomic profile in the kidney tissues of rats exposed to three NPs, showed differential spatial distribution of α-Enolase across the medulla and the cortex region with respect to the control group, suggesting an overexpression of α-Enolase. Overexpression of α-Enolase might be an indicative of cellular apoptosis in response to cytotoxicity caused due to NP perforation across the cellular membrane. In the present study, we propose that Fetuin-B might be considered a plasma biomarker to detect nanotoxicity at an early stage in a living system. Graphical abstract
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Key words
Fetuin-B,Nanoparticle toxicity,Biomarker,MALDI imaging,Tissue proteomics
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