Role of the luminal composition on intestinal metal toxicity, bioavailability and bioreactivity: An in vitro approach based on the cell line RTgutGC

Oldham, Dean; Black, T.N.; Stewart, Theodora J.; Minghetti, Matteo

doi:10.1016/j.aquatox.2023.106411

Cited by 4 publications

(5 citation statements)

References 59 publications

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“…Compared to the larvae, RTgill-W1 cells exposed in hypoosmotic medium showed similar sensitivity to Cd ( p = 0.6679), Cu ( p = 0.1349), and BAC ( p = 0.8891) but were more sensitive to ammonia ( p = 0.0076) and less to 3,4-DCA ( p < 0.0001). For Cu and Cd in isosmotic medium, the calcium concertation is higher (5.32 mM) than that in hypoosmotic medium (4.65 mM) and calcium has been shown to protect against divalent metal toxicity. , As previously shown, an increase in calcium concentration in the exposure medium results in a decrease in toxicity and bioavailability for some metals such as Cu and Cd . Additionally, increasing salinity has shown to decrease ammonia toxicity and organic toxicity and could explain RTgill-W1 cell’s increased sensitivity in hypoosmotic media.…”

Section: Results and Discussionmentioning

confidence: 84%

“…49,50 As previously shown, an increase in calcium concentration in the exposure medium results in a decrease in toxicity and bioavailability for some metals such as Cu and Cd. 51 Additionally, increasing salinity has shown to decrease ammonia toxicity 52 and organic toxicity 53 and could explain RTgill-W1 cell's increased sensitivity in hypoosmotic media. Overall, when comparing cells exposed in hypoosmotic conditions, an increase in sensitivity was measured for four of the five WET chemicals of concern, with BAC showing similar sensitivity to larvae.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Alternatives to Fish Acute Whole Effluent Toxicity (WET) Testing: Predictability of RTgill-W1 Cells and Fathead Minnow Embryos with Actual Wastewater Samples

Scott,

Mortensen,

Minghetti

2023

Environ. Sci. Technol.

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Toxicity assays using fish cells and embryos continue to gain momentum as a more ethical and informative alternative to fish acute toxicity testing. The goal of our study was to test the accuracy of RTgill-W1 cells and the fathead minnow (Pimephales promelas) embryos to predict actual whole effluent toxicity (WET) in the fathead minnow larvae. The three models were compared concurrently using samples of various origins and treatment types. Additionally, the toxicity of reference toxicants (Cd, Cu, NH 3 -N, 3,4-dichloraniline, and benzalkonium chloride) spiked into a nontoxic wastewater was compared. The toxicity of reference toxicants was tested in isosmotic and hypoosmotic exposure media in RTgill-W1 cells. Of the 28 wastewater samples, 14 induced a toxic response in fish larvae. Embryos predicted 11 of the 14 wastewater samples toxic to the larvae, whereas RTgill-W1 cells predicted the toxicity of all 14 toxic samples to the larvae. In addition, embryos and RTgill-W1 cells predicted toxicity in two and six additional samples, respectively, that were nontoxic to larvae. Exposures in hypoosmotic medium significantly increased sensitivity of RTgill-W1 cells to all reference toxicants, excluding benzalkonium chloride, compared to exposures in isosmotic medium and showed toxicity levels similar to that in larvae. Thus, hypoosmotic exposure medium should be considered for aquatic toxicity testing applications. Overall, both gill cell and embryo models predicted toxicity in the majority of wastewater samples toxic to larvae and demonstrated their applicability for regulatory WET testing.

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Section: Results and Discussionmentioning

confidence: 84%

Section: ■ Results and Discussionmentioning

confidence: 99%

Alternatives to Fish Acute Whole Effluent Toxicity (WET) Testing: Predictability of RTgill-W1 Cells and Fathead Minnow Embryos with Actual Wastewater Samples

Scott,

Mortensen,

Minghetti

2023

Environ. Sci. Technol.

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“…The uptake of Cd from a water body into fish depends on the metal speciation, with a free ion being the critical binding ligand [6,10,11], as well as on the cellular transport and uptake processes. To enter the cells of fish, metal ions have to pass across the lipid bilayer 2 of 15 of cell membranes, which show low ion permeability.…”

Section: Introductionmentioning

confidence: 99%

“…However, uptake pathways other than those that have evolved for Ca transport are also utilized by Cd. For instance, Liu et al [25] showed that a Zn 2+ /[HCO 3 − ] 2 symporter can facilitate Cd uptake into cells; Ohta and Ohba [17] pointed to the involvement of divalent metal transporter 1 (DMT1) in Cd transport; and Oldham et al [11] provided evidence for the role of zinc transporter 1. Finally, alternative to the absorption of Cd by transporters for inorganic metal species, Cd bound to sulfhydryl peptides can also be absorbed via membrane transport systems for mercaptides [14,[26][27][28].…”

Section: Introductionmentioning

confidence: 99%

“…In most cell types, it is present at millimolar concentrations and hence constitutes more than 90% of the cellular non-protein sulfhydryl groups [29][30][31]. Other sulfhydryl-containing cellular molecules that can form complexes with metal ions include, for instance, metallothioneins but also amino acids such as cysteine [11]. Sulfhydryls have a high affinity for metal ions, which they efficiently capture by forming chelates [32].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Glutathione and Sulfhydryl Groups in Cadmium Uptake by Cultures of the Rainbow Trout RTG-2 Cell Line

Lange,

Segner

2023

Cells

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The aim of this study is to investigate the role of cellular sulfhydryl and glutathione (GSH) status in cellular cadmium (Cd) accumulation using cultures of the rainbow trout cell line RTG-2. In a first set of experiments, the time course of Cd accumulation in RTG-2 cells exposed to a non-cytotoxic CdCl2 concentration (25 μM) was determined, as were the associated changes in the cellular sulfhydryl status. The cellular levels of total GSH, oxidized glutathione (GSSG), and cysteine were determined with fluorometric high-performance liquid chromatography (HPLC), and the intracellular Cd concentrations were determined with inductively coupled plasma mass spectrometry (ICP-MS). The Cd uptake during the first 24 h of exposure was linear before it approached a plateau at 48 h. The metal accumulation did not cause an alteration in cellular GSH, GSSG, or cysteine levels. In a second set of experiments, we examined whether the cellular sulfhydryl status modulates Cd accumulation. To this end, the following approaches were used: (a) untreated RTG-2 cells as controls, and (b) RTG-2 cells that were either depleted of GSH through pre-exposure to 1 mM L-buthionine-SR-sulfoximine (BSO), an inhibitor of glutathione synthesis, or the cellular sulfhydryl groups were blocked through treatment with 2.5 μM N-ethylmaleimide (NEM). Compared to the control cells, the cells depleted of intracellular GSH showed a 25% reduction in Cd accumulation. Likewise, the Cd accumulation was reduced by 25% in the RTG-2 cells with blocked sulfhydryl groups. However, the 25% decrease in cellular Cd accumulation in the sulfhydryl-manipulated cells was statistically not significantly different from the Cd accumulation in the control cells. The findings of this study suggest that the intracellular sulfhydryl and GSH status, in contrast to their importance for Cd toxicodynamics, is of limited importance for the toxicokinetics of Cd in fish cells.

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Role of UV radiation and oxidation on polyethylene micro- and nanoplastics: impacts on cadmium sorption, bioaccumulation, and toxicity in fish intestinal cells

Pinto,

Scott,

Hess

et al. 2024

Environ Sci Pollut Res

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This study investigated the role of ultraviolet (UV) radiation and oxidation in high-density polyethylene microplastics (2–15 μm) and nanoplastics (0.2–9.9 μm) (NMPs) on particle chemistry, morphology, and reactivity with cadmium (Cd). Additionally, toxicity of NMPs alone and with Cd was evaluated using RTgutGC cells, a model of the rainbow trout (Oncorhynchus mykiss) intestine. The role on NMPs on Cd bioaccumulation in RTgutGC cells was also evaluated. Dynamic light scattering indicated that after UV radiation NPs agglomerated size increased from 0.8 to 28 µm, and to 8 µm when Cd was added. Oxidized MPs agglomerated size increased from 11 and 7 to 46 and 27 µm in non-UV- and UV-aged oxidized MPs when adding Cd, respectively. Cd-coated particles exhibited generally significantly higher zeta potential than non-Cd-coated particles, while attenuated total reflectance–Fourier transform infrared spectroscopy showed that the functional chemistry of the particles was oxidized and modified after being exposed to UV radiation. Presence of NMPs resulted in a significant decrease in Cd bioaccumulation in RTgutGC cells (100.5–87.9 ng Cd/mg protein) compared to Cd alone (138.1 ng Cd/mg protein), although this was not quite significant for co-exposures with UV-aged NPs (105.7 ng Cd/mg protein). No toxicity was observed in RTgutGC cells exposed to NMPs alone for 24 h. Moreover, co-exposures with Cd indicated that NMPs reduce the toxicity of Cd. Altogether these results show that UV aging enhances NMP surface reactivity, increasing Cd absorption in solution, which resulted in a reduction in Cd bioavailability and toxicity.

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Role of the luminal composition on intestinal metal toxicity, bioavailability and bioreactivity: An in vitro approach based on the cell line RTgutGC

Cited by 4 publications

References 59 publications

Alternatives to Fish Acute Whole Effluent Toxicity (WET) Testing: Predictability of RTgill-W1 Cells and Fathead Minnow Embryos with Actual Wastewater Samples

Alternatives to Fish Acute Whole Effluent Toxicity (WET) Testing: Predictability of RTgill-W1 Cells and Fathead Minnow Embryos with Actual Wastewater Samples

The Role of Glutathione and Sulfhydryl Groups in Cadmium Uptake by Cultures of the Rainbow Trout RTG-2 Cell Line

Role of UV radiation and oxidation on polyethylene micro- and nanoplastics: impacts on cadmium sorption, bioaccumulation, and toxicity in fish intestinal cells

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