A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo–in vitro correlations

Kilgour, Joanne D.; Simpson, Sharon Anne; Alexander, D.J.; Reed, Celia J.

doi:10.1016/s0300-483x(99)00180-8

Cited by 14 publications

(15 citation statements)

References 23 publications

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“…In the present study as well as in all studies examining the expression of stress-induced HSPs in the OE (Kilgour et al, 2000;Carr et al, 2001Carr et al, , 2004Simpson et al, 2004Simpson et al, , 2005, the predominant cell type exhibiting HSP upregulation was the sustentacular cell. This observation is surprising given our hypothesis of a P2R role in HSP induction, as P2Rs are present on both ORNs and sustentacular cells.…”

Section: Discussionsupporting

confidence: 68%

“…Interestingly, intracellular ATP significantly decreased when the OE was damaged by toxic fumes, presumably through release by injured cells (Kilgour et al, 2000). Thus, we tested the hypothesis that harmful stimulation (in this case, strong odorant) evokes the release of ATP , first-second ectoturbinates; 2-4, second-fourth endoturbinates; onl, olfactory nerve layer; t, turbinate, nb, nerve bundle; SC, sustentacular cell layer; ORN, olfactory receptor neuron layer; HBC, horizontal basal cell; GBC, globose basal cell; OEC, olfactory ensheathing cell; OE, olfactory epithelium; RE, respiratory epithelium; BCL, basal cell layer; LP, lamina propria.…”

Section: Introductionmentioning

confidence: 99%

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Purinergic receptor antagonists inhibit odorant‐induced heat shock protein 25 induction in mouse olfactory epithelium

Hegg

Lucero

2005

Glia

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Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE). Extracellular ATP, a signal of cellular stress, induces the expression of HSPs via purinergic receptors. In the present study, in vivo odorant exposure (heptanal or R-carvone) led to a selective induction of HSP25 in glia-like sustentacular cells in the Swiss Webster mouse OE, as previously shown in rats (Carr et al., 2001). Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells. ATP released by acutely injured cells could act as an early signal of cell and tissue damage, causing HSP expression and initiating a stress signaling cascade to protect against further damage. Sustentacular cells have a high capacity to detoxify xenobiotics and thereby protect the olfactory epithelium from airborne pollutants. Thus, the robust, rapid induction of HSPs in sustentacular cells may help maintain the integrity of the OE during exposure to toxicants.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Purinergic receptor antagonists inhibit odorant‐induced heat shock protein 25 induction in mouse olfactory epithelium

Hegg

Lucero

2005

Glia

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“…Single liver slices were incubated in 24-well culture plates, in 0.5 ml supplemented Williams E medium, under an atmosphere of 95% O 2 :5% CO 2 . Slices were incubated at 43°C for 45 min and then transferred to 37°C for up to 24 h. After incubation, ETs and liver slices were prepared for analysis of ATP as described previously (Kilgour et al 1999). Protein pellets were solubilised in 0.1 ml 10% sodium dodecyl sulphate (SDS) and stored at )20°C.…”

Section: Preparation and Treatment Of Tissuesmentioning

confidence: 99%

“…Analytical techniques ATP concentrations in ETs and liver slices were determined by a luminometric method using firefly luciferase as described previously (Kilgour et al 1999). Protein concentrations were estimated using a detergent-compatible protein assay kit (BioRad Laboratories Ltd., Hemel Hempstead, UK).…”

Section: Preparation and Treatment Of Tissuesmentioning

confidence: 99%

“…This model has been characterised with regard to optimum culture conditions (Kilgour et al 1998a), maintenance of drug metabolising activity (Kilgour et al 1998b), and ability to accurately predict the upper respiratory tract toxicity of known and suspected nasal toxins (Kilgour et al 1999). A number of indices of toxicity/viability have been studied including ATP levels, intracellular potassium concentrations and lactate dehydrogenase release (Kilgour et al 1998a;Kilgour et al 1999). These parameters are good markers of cytotoxicity, but are relatively insensitive and lack the ability to detect early perturbations in cellular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Heat shock protein 70 in the rat nasal cavity: localisation and response to hyperthermia

Simpson

Alexander

Reed

2004

Archives of Toxicology

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Heat shock proteins (HSPs) are a group of proteins that are rapidly induced in response to physiological stress, including hyperthermia and exposure to toxicants. Thus they may provide a useful index of toxicity in in vitro systems for screening for toxicity. We have recently developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to localise HSP70 within the rat nasal cavity and to characterise its response to hyperthermia. Constitutively, HSP70 was found to be predominantly localised to the sustentacular cells, basal cells and Bowman's glands of the olfactory epithelium (OE), with the most intense immunohistochemical staining at levels 3 and 4 of the posterior of the rat nasal cavity. Ethmoturbinates (ETs) and liver slices were exposed to heat shock (37 degrees and 43 degrees C, respectively) for 45 min and then returned to normal culture temperatures (31 degrees and 37 degrees C, respectively) for 24 h. In ETs, HSP72 was maximally induced 4-fold at 4 h after heat shock, and levels then returned to those of control tissue. ATP concentrations were markedly decreased up to 4 h after heat shock and then returned to control levels. In contrast, HSP72 levels in liver slices increased and ATP levels decreased steadily throughout the 24 h culture period. ETs were also able to withstand a 45-min heat shock at 43 degrees C, that is 12 degrees C above normal culture temperature. Incubation of ETs with cycloheximide prior to heat shock reduced the ability of the OE to recover from heat shock at 37 degrees C. Thus the OE of the rat nasal cavity expresses HSP72, and this protein appears to play an important role in the ability of the tissue to withstand hyperthermia.

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Biotoxicity of Metal Oxide Nanoparticles

Fond

Meyer

2003

Nanotechnologies for the Life Sciences

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The sections in this article are Introduction Nanoparticles in the Environment How Nanoparticles are Introduced into Mammalian Systems Health Threats Nanomaterials and Biotoxicity Iron Oxide Titanium Dioxide Dark Studies UV Irradiation Studies Other Metal Oxides Conclusions Acknowledgment

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A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo–in vitro correlations

Cited by 14 publications

References 23 publications

Purinergic receptor antagonists inhibit odorant‐induced heat shock protein 25 induction in mouse olfactory epithelium

Purinergic receptor antagonists inhibit odorant‐induced heat shock protein 25 induction in mouse olfactory epithelium

Heat shock protein 70 in the rat nasal cavity: localisation and response to hyperthermia

Biotoxicity of Metal Oxide Nanoparticles

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