Abstract
There is increasing evidence that titanium dioxide (TiO2) nanoparticles (NPs) present in water or diet can be taken up by fish and accumulate in internal organs including the liver. However, their further fate in the organ is unknown. This study provides new insights into the interaction, uptake mechanism, intracellular trafficking, and fate of TiO2 NPs (Aeroxide® P25) in fish liver parenchymal cells (RTL-W1) in vitro using high-resolution transmission electron microscopy (TEM) and single particle inductively coupled plasma mass spectrometry (spICP-MS) as complementary analytical techniques. The results demonstrate that following their uptake via caveolae-mediated endocytosis, TiO2 NPs were trafficked through different intracellular compartments including early endosomes, multivesicular bodies, and late endosomes/endo-lysosomes, and eventually concentrated inside multilamellar vesicles. TEM and spICP-MS results provide evidence that uptake was nano-specific. Only NPs/NP agglomerates of a specific size range (~ 30–100 nm) were endocytosed; larger agglomerates were excluded from uptake and remained located in the extracellular space/exposure medium. NP number and mass inside cells increased linearly with time and was associated with an increase in particle diameter suggesting intracellular agglomeration/aggregation. No alterations in the expression of genes regulated by the redox balance-sensitive transcription factor Nrf-2 including superoxide dismutase, glutamyl cysteine ligase, glutathione synthetase, glutathione peroxidase, and glutathione S-transferase were observed. This shows that, despite the high intracellular NP burden (~ 3.9 × 102 ng Ti/mg protein after 24 h) and NP-interaction with mitochondria, cellular redox homeostasis was not significantly affected. This study contributes to a better mechanistic understanding of in vitro particokinetics as well as the potential fate and effects of TiO2 NPs in fish liver cells.
Highlights
TiO2 NPs are emerging environmental contaminants to which aquatic biota including fish will become increasingly exposed (Johnson et al 2011; Kaegi et al 2008; Kiser et al 2009; Mueller and Nowack 2008; Peters et al 2018; Weir et al 2012)
The hydrodynamic sizefrequency distribution by number of Bovine serum albumin (BSA)-stabilized TiO2 NPs in L-15 medium at the beginning (t = 0) and the end of the exposure period (t = 24 h) determined by Dynamic light scattering (DLS) is shown in Fig. 1c
We describe in detail the interaction, uptake, and intracellular fate of one of the most frequently studied TiO2 NPs (Aeroxide® P25) in fish liver cells (RTL-W1 cells)
Summary
TiO2 NPs are emerging environmental contaminants to which aquatic biota including fish will become increasingly exposed (Johnson et al 2011; Kaegi et al 2008; Kiser et al 2009; Mueller and Nowack 2008; Peters et al 2018; Weir et al 2012). Ramsden et al (2009) measured a significant increase in hepatic Ti concentration (approximately 0.05–0.1 mg Ti g−1 dry weight tissue) in rainbow trout following dietary exposure to TiO2 NPs (10 mg TiO2 kg−1 food). Their results showed limited elimination of Ti from the liver after 2 weeks of depuration (Ramsden et al. Environ Sci Pollut Res (2019) 26:15354–15372. We recently observed a TiO2 NPresembling electron-dense object in the perisinusoidal space of brown trout liver fed TiO2 NP-containing diet suggesting that TiO2 NPs can cross the sinusoidal endothelium and come in direct contact with liver parenchymal cells (manuscript under review (Lammel et al 2019)). These observations raise several questions: Are TiO2 NPs that reach the liver endocytosed by liver parenchymal cells? Which is the size spectrum of TiO2 NPs that can be taken up? Through which endocytic mechanism are they taken up? Which is their further fate and destination inside the cell? Can they be eliminated or will they accumulate with time? And, can accumulation result in adverse effects?
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