title: Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML) is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.
authors.affiliation: Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Robbe
authors.affiliation: Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tassin
authors.affiliation: Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Carpentier
authors.affiliation: Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Anne-Emilie
authors.initials: AE
authors.lastname: Declèves
authors.affiliation: Department of Pneumology, Erasme Hospital, 1070 Brussels, Belgium.
authors.forename: Zita Léa
authors.initials: ZL
authors.lastname: Mekinda Ngono
authors.affiliation: Laboratory of Histology, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Nonclercq
authors.affiliation: Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Legrand
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D006801:Humans; D000069555:Injection, Intratympanic; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
chemical_list: D001761:Bleomycin