Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions. (July 2015)

• Record Type: Journal Article
• Authors: Della Latta, Veronica; Cecchettini, A.; Del Ry, S.; Morales, M.A.
• Is Part Of: Pharmacological research. Volume 97(2015:Jul.)
• Page Start: 122
• Page End: 130
• Publication Date: 2015-07
• Subjects: AF-1 antiflammin-1 -- BALF bronchoalveolar lavage fluid -- BLH bleomycin hydrolase -- BLM bleomycin -- BLT bleomycin lung toxicity -- CCL12 chemokine ligand-12 -- CCL2 chemokine ligand-2 -- COL1 type 1 collagen -- CTGF connective tissue growth factor -- DNA deoxyribonucleic acid -- E-64 epoxide-64 -- ECM extracellular matrix -- EGF epidermal growth factor -- EGFR epidermal growth factor receptor -- EGFR-TKIs EGFR -- EMT epithelial–mesenchymal transition -- EndMT endothelial–mesenchymal transition -- ERK extracellular signal-regulated kinases -- ET-1 Endothelin-1 -- FGF-2 fibroblast growth factor-2 -- FVC forced vital capacity -- GM-CSF granulocyte-macrophage colony-stimulating factor -- HRCT high-resolution computed tomography -- HSP47 heat shock protein 47 -- IGF-II insulin-like growth factor-2 -- IIPs idiopathic interstitial pneumonias -- IL-4 interleukin-4 -- IL-6 interleukin-6 -- IL-12 interleukin-12 -- IL-13 interleukin-13 -- IL-22 interleukin-22 -- ILDs interstitial lung diseases -- IFN-γ interferon-gamma -- iNOS inducible nitric oxide synthase -- IPF idiopathic pulmonary fibrosis -- LOX Lysyl oxidase -- LOX2 Lysyl Oxidase-like 2 -- LPA lysophosphatidic acid -- LPA-1 lysophosphatidic acid 1 -- MMP-7 matrix metalloproteinase-7 -- MOL molsidomine -- NAC N-acetylceysteine -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B-cells -- PBA pyrimidoblamic acid -- PDGF platelet-derived growth factor -- PDGFR platelet-derived growth factor receptor -- PF pulmonary fibrosis -- PH pulmonary hypertension -- RNS reactive nitrogen species -- ROCK RhoA/Rho-kinase -- ROS reactive oxygen species -- SHH sonic hedgehog -- Smad2/3 Small mother against decapentaplegic -- TGF-α transforming growth factor alpha -- TGF-β transforming growth factor beta -- TGF-β1 transforming growth factor beta 1 -- TNF-α tumor necrosis factor alpha -- UIP usual interstitial pneumonia -- VEGF vascular endothelial growth factor; Bleomycin (BLM) -- Pulmonary fibrosis -- Transforming growth factor beta (TGF-β) -- Idiopathic pulmonary fibrosis (IPF) -- Extracellular matrix (ECM) -- Animal models; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2015.04.012
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Bleomycin (BLM) is a drug used to treat different types of neoplasms. BLM's most severe adverse effect is lung toxicity, which induces remodeling of lung architecture and loss of pulmonary function, rapidly leading to death. While its clinical role as an anticancer agent is limited, its use in experimental settings is widespread since BLM is one of the most widely used drugs for inducing lung fibrosis in animals, due to its ability to provoke a histologic lung pattern similar to that described in patients undergoing chemotherapy. This pattern is characterized by patchy parenchymal inflammation, epithelial cell injury with reactive hyperplasia, epithelial–mesenchymal transition, activation and differentiation of fibroblasts to myofibroblasts, basement membrane and alveolar epithelium injuries. Several studies have demonstrated that BLM damage is mediated by DNA strand scission producing single- or double-strand breaks that lead to increased production of free radicals. Up to now, the mechanisms involved in the development of pulmonary fibrosis have not been fully understood; several studies have analyzed various potential biological molecular factors, such as transforming growth factor beta 1, tumor necrosis factor alpha, components of the extracellular matrix, chaperones, interleukins and chemokines. The aim of this paper is to review the specific characteristics of BLM-induced lung fibrosis in different animal models and to summarize modalities and timing of in vivo drug administration. Understanding the mechanisms of BLM-induced lung fibrosis and of commonly used therapies for counteracting fibrosis provides an opportunity for translating potential molecular targets from animal models to the clinical arena.