Mouse model of paraquat-poisoned lungs and its gene expression profile

Tomita, Masafumi; Okuyama, Toshiko; Katsuyama, Hironobu; Miura, Yoshie; Nishimura, Yasumasa; Hidaka, Kazuo; Otsuki, Takemi; Ishikawa, Takaki

doi:10.1016/j.tox.2006.12.005

Cited by 74 publications

(55 citation statements)

References 34 publications

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“…Lung samples (20 mg/ml) from the control and experimental animals were homogenized in 10 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Sigma), 20 mM HEPES (pH 7.5) plus 150 mM NaCl. Electrophoresis using 7.2% polyacrylamide gels containing 2 mg/ml gelatin in non-reducing conditions (4˚C) was employed to determine the molecular weight distribution and general gelatinase activity of lung homogenates using methods similar to those described by Hibbs et al (13). Samples were run on duplicate gels for ~1.5 h at 100 V with 10-well minigels and a 4% stacking gel.…”

Section: Fluorimeter-based Quantitive Rt-pcr Assaymentioning

confidence: 99%

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

Wang

et al. 2011

Mol Med Rep

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Abstract. Paraquat (PQ)-induced pulmonary toxicity is known to result in pulmonary edema, infiltration of inflammatory cells and damage to the alveolar epithelium, which may progress to severe fibrosis. Matrix metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), which degrade and remodel the excess extracellular matrix, are believed to play an important role in the development of fibrotic tissue. In this study, we examined the sequential expression of MMP-2, MMP-9 and TIMP-1 in a rat model of pulmonary fibrosis induced by PQ. Adult male Sprague-Dawley rats were treated intraperitoneally with PQ (20 mg/kg) and saline (control group). Rats were sacrificed at days 1, 3, 7 and 21 after the PQ treatment. Lungs were excised for histological evaluation and immunohistochemical analyses, as well as the determination of collagen content, gene expression by fluorimeter-based quantitive RT-PCR assay and gelatinolytic activity by zymography. Lung MMP-2 and -9 mRNA expression progressively increased and reached a peak on day 7 after PQ treatment, while TiMP-1 mrna levels in the PQ-treated lungs reached a peak on day 21 after modeling. Lung zymography revealed an increase in progelatinase B, progelatinase a and their active forms. In conclusion, unbalanced MMP/TIMP-1 expression and excessive gelatinolytic activity contribute to PQ-induced pulmonary fibrosis. Their precise role should be studied in depth as they may represent relevant therapeutic targets for PQ poisoning-induced pulmonary fibrosis.

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Section: Fluorimeter-based Quantitive Rt-pcr Assaymentioning

confidence: 99%

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

Wang

et al. 2011

Mol Med Rep

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“…The C57BL/6 mouse strain has also been used for toxicology studies. When paraquat solution was applied to these mice through their nares, they showed lung pathology similar to those suffering from paraquat toxicity (Tomita et al, 2007).…”

Section: Development Of Animal Modelsmentioning

confidence: 90%

Herbicides and the Risk of Neurodegenerative Disease

Muthukumaran¹,

Laframboise²,

Pandey³

2011

Herbicides - Mechanisms and Mode of Action

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“…Paraquat causes severe lung injury and elicits several changes in gene expression in the lung (Ishida et al, 2006;Tomita et al, 2007), during the destructive phase (i.e., 5 days post-exposure to PQ) that precedes the development of fibrosis. Cytokines, chemokines, and growth factors may contribute to the pathogenesis of pulmonary fibrosis (Smith et al, 1995;Martinet et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Changes in the expression levels of several genes in the lungs of PQ-exposed mice have been reported (Satomi et al, 2004;Tomita et al, 2007). We examined the levels of lung injury-related enzymes 5 days post-PQ treatment with or without DDS pretreatment.…”

Section: Pretreatment With Dds Modulates the Levels Of Oxidative Damamentioning

confidence: 99%

Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury

et al. 2011

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Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ.Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1α (MIP-1α), and transforming growth factor-β (TGF-β). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cμ (PKCμ). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.

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Mouse model of paraquat-poisoned lungs and its gene expression profile

Cited by 74 publications

References 34 publications

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

Herbicides and the Risk of Neurodegenerative Disease

Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury

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