title: Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology.
abstract: Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI) and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR). In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.
authors.affiliation: Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Egger
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Christelle
authors.initials: C
authors.lastname: Gérard
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jarman
authors.forename: Gabor
authors.initials: G
authors.lastname: Jarai
authors.forename: Agnès
authors.initials: A
authors.lastname: Feige
authors.forename: Thomas
authors.initials: T
authors.lastname: Suply
authors.forename: Arthur
authors.initials: A
authors.lastname: Micard
authors.forename: Andrew
authors.initials: A
authors.lastname: Dunbar
authors.forename: Bruno
authors.initials: B
authors.lastname: Tigani
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009055:Mouth / Q000473:pathology*; D010614:Pharynx / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013396:Suction; D013997:Time Factors
chemical_list: D001761:Bleomycin