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In situ assessment of oxidant and nitrogenic stress in bleomycin pulmonary fibrosis

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Abstract

Reactive oxygen species (ROS) and nitric oxide (NO) have a role in the development of pulmonary fibrosis after bleomycin administration. The ROS production induces an antioxidant response, involving superoxide dismutases (SODs), catalase, and glutathione peroxidases. We compared in situ oxidative burden and antioxidant enzyme activity in bleomycin-injured rat lungs and normal controls. ROS expression and catalase, glucose-6-phosphate-dehydrogenase (G6PHD), and NOS/NADPH-diaphorase activity were investigated by using histochemical reactions. Nitric oxide synthase (e-NOS and i-NOS) and SOD (MnSOD, Cu/ZnSOD, ECSOD) expression was investigated immunohistochemically. After treatment ROS production was enhanced in both phagocytes and in type II alveolar epithelial cells. Mn, Cu/Zn, and ECSOD were overexpressed in parenchymal cells, whereas interstitium expressed ECSOD. Catalase and G6PHD activity was moderately increased in parenchymal and inflammatory cells. NOS/NADPH-d activity and i-NOS expression increased in alveolar and bronchiolar epithelia and in inflammatory cells. It can be suggested that the concomitant activation of antioxidant enzymes is not adequate to scavenge the oxidant burden induced by bleomycin lung damage. Inflammatory cells and also epithelial cells are responsible of ROS and NO production. This oxidative and nitrosative stress may be a substantial trigger in TGF-β1 overexpression by activated type II pneumocytes, leading to fibrotic lesions.

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Acknowledgements

This paper is supported by a “Ricerca Corrente” research grant from IRCCS Policlinico San Matteo.

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Authors and Affiliations

  1. Department of Animal Biology, University of Pavia, Piazza Botta 10, 27100, Pavia, Italy

    Sergio Barni & Carla Fenoglio

  2. Department of Respiratory Diseases, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100, Pavia, Italy

    Simona Inghilleri & Tiberio Oggionni

  3. Department of Pathology, IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy

    Patrizia Morbini

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  1. Simona Inghilleri
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  2. Patrizia Morbini
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  3. Tiberio Oggionni
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  4. Sergio Barni
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  5. Carla Fenoglio
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Correspondence to Carla Fenoglio.

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Inghilleri, S., Morbini, P., Oggionni, T. et al. In situ assessment of oxidant and nitrogenic stress in bleomycin pulmonary fibrosis. Histochem Cell Biol 125, 661–669 (2006). https://doi.org/10.1007/s00418-005-0116-7

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