Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells

Konsoula, Roula; Barile, Frank A.

doi:10.1016/j.tiv.2005.03.006

Cited by 105 publications

(82 citation statements)

References 23 publications

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“…Studies observing ionic compounds indicate that cytotoxicity occurs before TEER becomes compromised (Konsoula and Barile 2005). Notably, the cytotoxicity of metallic NPs is frequently associated with leaching metal ions (Sabella et al 2014;Zook et al 2012;Setua et al 2014).…”

Section: Resultsmentioning

confidence: 99%

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

et al. 2016

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Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 lg/mL of Sb 2 O 3 , Mn 3 O 4 and TiO 2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co 3 O 4 and ZnO NPs had moderate effects and CuO NPs were toxic below 100 lg/mL (24 h EC 25 = 11 for A549 and 71 lg/mL for Caco2). The long-term monitoring (up to 9 days) of cells to NPs revealed that the toxic effects of Mn 3 O 4 and Sb 2 O 3 NPs remarkably increased over time. The 9 day EC 50 values for Sb 2 O 3 NPs were 22 and 48 lg/mL for A549 and Caco2 cells; and for Mn 3 O 4 NPs were 47 and 29 lg/mL for A549 and Caco2 cells, respectively. In general, the sensitivity of the cell lines in the resazurin assay was comparable. Trans epithelial electrical resistance (TEER) measurements were performed for both cell types exposed to Co 3 O 4 , Sb 2 O 3 and CuO NPs. In TEER assay, the Caco2 cells were more susceptible to the toxic effects of these NPs than A549 cells, where the most toxic NPs were the Sb 2 O 3 NPs: the permeability of the Caco2 cell layer exposed to 10 lg/mL Sb 2 O 3 NPs already increased after 24 h of exposure.Electronic supplementary material The online version of this article

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Section: Resultsmentioning

confidence: 99%

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

et al. 2016

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“…MTT, LDH) can predict irritancy and delayed toxicity of harmful agents (13). Nevertheless, cytotoxicity data alone are not necessarily predictive of in vivo issues (14), but complemented with results of morphology studies, the in vivo toxicity data may be estimated (15). Even if titanate nanotubes are unpermeable on intestinal cell layer, they deliver drug particles to intestinal cell surface and can also increase the solubility of active substances.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Cytotoxic Effects of Titanate Nanotubes on Caco-2 Cells

et al. 2014

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Abstract. Titanate nanotubes can be used as drug delivery systems, but limited information is available on their interactions with intestinal cells. In this study, we investigated the cytotoxicity and cellular uptake of titanate nanotubes on Caco-2 monolayers and found that up to 5 mg/ml concentration, these nanotubes are not cytotoxic and not able to permeate through the intestinal cell layer. Transmission electron microscopic experiments showed that titanate nanotubes are not taken up by cells, only caused a highdensity granulation on the surface of the endoplasmic reticulum. According to these results, titanate nanotubes are suitable systems for intestinal drug delivery.

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“…studies were performed as previously described Barile, 2005 and2007). Briefly, proliferating MA cultures were seeded onto 12-well transwell polycarbonate inserts as described above.…”

Section: Paracellular Permeability (Pp) Studies-ppmentioning

confidence: 99%

“…We recently used Caco-2 monolayers (Konsoula and Barile, 2005) and IEC-18 cells (Konsoula and Barile, 2007) as in vitro models for comparing PP with AC of 20 chemicals. Caco-2, an immortal cell line originating from human colon, demonstrate transepithelial electrical resistance (TEER) values that are relatively higher than IEC-18 monolayers cultured from the small intestine.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of in vitro cytotoxicity and paracellular permeability of intact monolayers with mouse embryonic stem cells

Calabro

Konsoula

Barile

2008

Toxicology in Vitro

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Mouse embryonic stem (mES) cells were induced to form intact monolayers in cell culture inserts, using combinations of extracellular matrix (ECM) components and growth factors (GFs). Progressive formation of intact monolayers was monitored using transepithelial electrical resistance (TEER) and passage of paracellular permeability (PP) markers. The mES cells were initially inoculated on inactivated mouse embryonic fibroblasts (MEFs) plus leukemia inhibitory factor (LIF). At 75% confluence, cells were passaged in the absence of MEF and LIF to stimulate formation of rounded multicellular aggregates (MA). After 4 days, cultures containing MA were transferred to culture inserts coated with ECM components only, and grown in the presence of selected individual GFs. An additional 10 to 14 days revealed confluent monolayers with TEER values of 500-700 ohmscm 2 (Ω-cm 2 ). Monolayers grown on inserts coated with ECM components, such as fibronectin or collagen-IV, in the presence of epidermal growth factor or keratinocyte growth factor in the medium, yielded the highest TEER measurements when compared to cultures grown without GFs or ECM. Acute cytotoxicity (AC) studies with confluent monolayers of mES cells in 96-well plates indicated that there is a high correlation (R 2 =0.91) between cell viability and TEER for 24-h exposure time. Also, decrease in TEER is inversely proportional with increase in PP of markers. In comparison to standardized Registry of Cytotoxicity (RC) data and TEER measurements, MTT IC 50 values for mES cells are lower. Thus, at equivalent concentrations for the same chemicals, cell viability decreases before the integrity of the monolayer is compromised. This system represents a novel approach for the manipulation of mES cells toward specific intact monolayers, as an in vitro model for biological monolayer formation, and most importantly, for applications to cytotoxicity testing.

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Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells

Cited by 105 publications

References 23 publications

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

Investigation of the Cytotoxic Effects of Titanate Nanotubes on Caco-2 Cells

Evaluation of in vitro cytotoxicity and paracellular permeability of intact monolayers with mouse embryonic stem cells

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