Airway inflammatory and immunological events in a rat model exposed to toluene diisocyanate

Kouadio, Kouame; Zheng, Kui; Tuekpe, Mallet K.-N.; Todoriki, Hidemi; Ariizumi, Makoto

doi:10.1016/j.fct.2005.03.005

Cited by 15 publications

(19 citation statements)

References 35 publications

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“…In our study we have found increase in levels of these cells in blood of TDI-control rats, which were found to be decreased significantly by drug treatment. On the other hand, Kouadio et al (2005) found that eosinophils and neutrophils were increased 17.2 and 4.6 times, respectively, in the BAL fluids of rats exposed to 0.38 ppm TDI. In our study, animals in the TDI-control group showed significant increases in the number of total and differential leukocyte counts.…”

Section: Discussionmentioning

confidence: 92%

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Effect ofMoringa oleiferaLam. Seed Extract on Toluene Diisocyanate-Induced Immune-Mediated Inflammatory Responses in Rats

Mahajan

Mali

Mehta

2007

Journal of Immunotoxicology

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Moringa oleifera Lam. is a small tree cultivated throughout India. We have investigated the effect of ethanolic extract of seeds of Moringa oleifera (MOEE, an herbal remedy) on the potential prevention of immune-mediated inflammatory responses in toluene diisocyanate (TDI as antigen)-induced asthma in Wistar rats. Rats were divided into five different groups (n = 8/group): Group-I = unsensitized control; Group-II = TDI control/vehicle; Group-III = dexamethasone (DXM) 2.5 mg/kg; and, Groups IV and V = 100 mg/kg and 200 mg/kg body weight [BW] of MOEE, respectively. All rats (except unsensitized controls) were sensitized by intranasal application of 10% TDI to induce airway hypersensitivity. Animals in Groups II-V were given their respective drug treatment per os from 1 wk prior to initiation of sensitization until the day of final provocation with 5% TDI. After this last challenge, all rats were examined for hyperreactivity symptoms and then sacrificed to determine their total and differential leucocytes in blood and bronchoalveolar (BAL) fluid and levels of TNF∝, IL-4, and IL-6 in their BAL and serum. Homogenates of one lung lobe from each animal were utilized to assess oxidative stress; a separate lobe underwent histologic examination to assess airway inflammatory status. The results suggest that asthmatic symptoms were found in TDI control rats only, while both MOEE-and DXM-treated rats did not manifest any airway abnormality. In MOEE-and DXM-treated rats, neutrophil and eosinophil levels in the blood were decreased significantly; levels of total cells and each different cell in their BAL fluid were markedly decreased as compared to those in TDI controls. TNFα, IL-4, and IL-6 were predominant in serum as well as in BAL fluids in TDI controls, but these levels were reduced significantly by MOEE treatment. The antioxidant activity in relation to antiinflammatory activity of the extract and histopathological observations also reflected a protective effect. Based on the above findings and observations, it can be concluded that Moringa oleifera may possess some beneficial properties that act against chemically stimulated immune-mediated inflammatory responses that are characteristic of asthma in the rat.

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Section: Discussionmentioning

confidence: 92%

“…Plitnick et al (2005), using molecular immunology, compared cytokine mRNA responses in the auricular lymph nodes of BALB/c mice following treatment with isocyanates. Kouadio et al (2005) exposed Wistar rats to TDI vapor (4 hr/d for 5 consecutive days) and then quantified IL-2, -4, and -6 levels in their BAL fluid.…”

Section: Discussionmentioning

confidence: 99%

Effect ofMoringa oleiferaLam. Seed Extract on Toluene Diisocyanate-Induced Immune-Mediated Inflammatory Responses in Rats

Mahajan

Mali

Mehta

2007

Journal of Immunotoxicology

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“…Often small animals, like mice or rats, are exposed to the product for a longer periods of time (Wagner et al, 2006;Lee et al, 2007) or for shorter periods of time to assess acute effects (Dong et al, 2005;Kouadio et al, 2005). As in human trials (De Backer et al, 2007a) a trend is emerging in animal studies towards accurate computer models describing the animals' physiological behavior (Schroeter et al, 2006;Galle et al, 2007).…”

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confidence: 99%

Study of the Variability in Upper and Lower Airway Morphology in Sprague–Dawley Rats Using Modern Micro‐CT Scan‐Based Segmentation Techniques

Backer

Vos

Burnell

et al. 2009

The Anatomical Record

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Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans.

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“…This discrepancy may be explained by a difference in number of instillations due to a slightly shorter protocol in our study. Other experimental studies have supported the notion that neutrophils are an important component in airway inflammation in rats after repeated airway exposures to isocyanates [27, 28]. From clinical studies, it is reported that induced sputum from patients diagnosed with occupational asthma caused by low-dose exposure to isocyanates increased the number of neutrophils rather than eosinophils [29],indicating a prominent presence of neutrophils also in human isocyanate-induced airway disease.…”

Section: Discussionmentioning

confidence: 72%

Rats Repeatedly Exposed to Toluene Diisocyanate Exhibit Immune Reactivity against Methyl Isocyanate-Protein Conjugates

Elfsmark

Koch

Gustafsson

et al. 2009

Int Arch Allergy Immunol

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Background: Volatile monoisocyanates are formed through thermal degradation when products containing polyurethane are heated. Repeated exposure to diisocyanates, such as toluene diisocyanate (TDI) are a well-known cause of occupational asthma. However, although monoisocyanates are abundant in occupational settings, there are few data concerning their ability to provoke immune reactions and asthma. We compared immune reactivity and respiratory disease following single or repeated inhalation exposures to the monoisocyanates methyl isocyanate (MIC) and isocyanic acid (ICA) with the effects of TDI. Methods:Isocyanates were administrated either as single vapor exposures or as repeated intranasal instillations in rats. Adverse health effects were monitored by analyzing airway inflammation, respiratory function and weight gain. Immune reactivity caused by repeated exposures was studied by analysis of isocyanate-specific antibodies and airway infiltration of immune competent cells. Results: Repeated exposures to TDI induced airway infiltration of neutrophils and lymphocytes, while neither MIC nor ICA provoked a detectable inflammatory response. Antibodies against isocyanate-albumin conjugates were detected in serum after both exposures to TDI and MIC, but not to ICA. TDI-exposed rats also displayed IgG antibodies against MIC-albumin conjugates. Even though MIC did not induce airway inflammation, single exposure provoked an increase in airway resistance and repeated exposures caused weight loss similar to that of TDI. Conclusions: Airway exposure to TDI produces an antibody response not only against TDI but also against MIC-protein conjugates. This indicates that immune reactivity against abundant monoisocyanates in occupational environments can occur in individuals pre-sensitized with low abundance but highly sensitizing diisocyanates.

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Airway inflammatory and immunological events in a rat model exposed to toluene diisocyanate

Cited by 15 publications

References 35 publications

Effect ofMoringa oleiferaLam. Seed Extract on Toluene Diisocyanate-Induced Immune-Mediated Inflammatory Responses in Rats

Effect ofMoringa oleiferaLam. Seed Extract on Toluene Diisocyanate-Induced Immune-Mediated Inflammatory Responses in Rats

Study of the Variability in Upper and Lower Airway Morphology in Sprague–Dawley Rats Using Modern Micro‐CT Scan‐Based Segmentation Techniques

Rats Repeatedly Exposed to Toluene Diisocyanate Exhibit Immune Reactivity against Methyl Isocyanate-Protein Conjugates

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