Study of lung toxicity in rats exposed to silica powder with different hard metal constituents

Abstract

The objective of this study was to assess the lung toxicity induced by the inhalation of different hard metal constituents and silica powder and screen for potential toxicity biomarkers. Rats were randomly divided into saline, cobalt, tungsten carbide, silica, and hard metal (HM) groups and were administered a single 10-mg dose of the respective treatments. After 8 weeks, the lung tissue structure in the HM group was deformed, numerous nucleated giant and epithelial-like cells appeared in the stroma, and the computed tomography scanning images appeared abnormal. Krebs von den Lungen-6 (KL-6), transforming growth factor (TGF)-β1, and TGF-β2 expression in bronchoalveolar lavage fluid (BALF) significantly differed between the groups (p < 0.05). Serum KL-6 and TGF-β1, but not TGF-β2, levels significantly differed between some groups (p < 0.05). We observed multinucleated giant cells in the rat lung tissue. While the serum and BALF levels of KL-6 and TGF-β2 are not highly specific, TGF-β1 may be a valuable reference diagnostic marker in HM lung disease.

Keywords

Hard metal lung disease tungsten carbide cobalt silicon dioxide KL-6 transforming growth factor

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References

Anttila

Sutinen

Paananen

. (1986) Hard metal lung disease: a clinical, histological, ultrastructural and X-ray microanalytical study. European Journal of Respiratory Diseases 69: 83–94.

Chen

Chou

Hsu

. (2005) Transforming growth factor-beta l upregulation is independent of angiotensin in paraquat-induced lung fibrosis. Toxicology 216: 181–187.

Cugell

(1992) The hard metal diseases. Clinics in Chest Medicine 13: 269–279.

Davison

Haslam

Corrin

. (1983) Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests. Thorax 38: 119–128.

Fine

Goldstein

(1987) The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts. Journal of Biological Chemistry 262: 3897–3902.

Gauldie

Galt

Bonniaud

. (2003) Transfer of the active form of transforming growth factor-beta 1 gene to newborn rat lung induces changes consistent with bronchopulmonary dysplasia. American Journal of Pathology 163: 2575.

Gotway

Golden

Warnock

. (2002) Hard metal interstitial lung disease: high-resolution computed tomography appearance. Journal of Thoracic Imaging 17: 314–318.

Ishida

Takayasu

Kimura

. (2005) Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice. Legal Medicine (Tokyo) 8: 102–109.

Kasper

Seidel

Knels

. (2004) Early signs of lung fibrosis after in vitro treatment of rat lung slices with CdC12 and TGF-beta l. Histochemistry and Cell Biology 121: 131.

10.

Kim

Lee

. (2001) Imaging of occupational lung disease. Radiographics 21: 1371–1391.

11.

Kobayashi

Kitamura

(1995) KL-6: a serum maker for interstitial pneumonia. Chest 108: 311–315.

12.

Kobayashi

Kitamura

(1996) Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest 109: 1276–1282.

13.

Kohno

Akiyama

Kyoizumi

. (1988) Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Japanese Journal of Clinical Oncology 18: 203–216.

14.

Lahaye

Demedts

vanden Oever

. (1984) Lung diseases among diamond polishers due to cobalt. The Lancet 8369: 156–157.

15.

Azuma

Usuki

. (2005) EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-beta signaling in lung fibroblasts. Respiratory Research 7: 16.

16.

Lichtenberger

Montague

Hunter

. (2005) NAC and DTT promote TGF-(beta) 1 monomer formation: demonstration of competitive binding. Journal of Inflammation (London) 3: 7.

17.

Nemery

Verbeken

Demedts

(2001) Giant cell interstitial pneumonia (hard metal lung disease, cobalt lung). Seminars in Respiratory and Critical Care Medicine 22: 435–448.

18.

Ohnishi

Yokoyama

Kondo

. (2002) Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. American Journal of Respiratory and Critical Care Medicine 165: 378–381.

19.

Ohshimo

Bonella

Sommerwerck

. (2011) Comparison of serum KL-6 versus bronchoalveolar lavage neutrophilia for the diagnosis of bronchiolitis obliterans in lung transplantation. The Journal of Heart and Lung Transplantation 30: 1374–1380.

20.

Reddy

Gorelick

Christianson

(1970) Giant cell interstitial pneumonia (GIP). Chest 58: 319–325.

21.

Tanaka

Moriyama

Terada

. (2014) An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease. BMJ Open 4: e004407.

22.

Van den Brule

Misson

Buhling

. (2005) Overexpression of cathepsin K during silica-induced lung fibrosis and control by TGF-beta. Respiratory Research 6: 84.

23.

Vij

Noth

(2012) Peripheral blood biomarkers in idiopathic pulmonary fibrosis. Translational Research 159: 218–227.

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