title: Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice.
abstract: OBJECTIVE
  Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain.
  
  
  METHODS
  Mice were divided into two groups, BLM-treated and normal control. BLM via OPA (2 IU/kg) was used to induce PF. Water for injection was used as a vehicle in control animals. Body weights were measured once in a week, and the study was continued for 21 days. At the end of the study, animals were euthanized and bronchoalveolar lavage fluid was collected and subjected to lymphocytes count, estimation of albumin and protein levels. Lung tissues were collected, and various biochemical assays (malondialdehyde, glutathione, nitric oxide, hydroxyproline) and molecular techniques including ELISA and Western blot were performed to investigate the effect of OPA-BLM. Further, histopathology and Masson's trichrome staining techniques were performed in lung sections.
  
  
  RESULTS
  OPA administration of BLM in Swiss mice significantly induced PF, evident from lung index and morphology. Several oxidative stress parameters and hydroxyproline assay revealed the significant (P< 0.05) induction of PF. Further results obtained from histopathology, Masson's trichrome staining, ELISA, and Western blot confirmed the significant induction of PF via OPA-BLM.
  
  
  CONCLUSIONS
  BLM administration by OPA route in Swiss mice can be used as a simple, homogeneous, and noninvasive model of inducing PF and to investigate the effect of various anti-fibrotic agents as an alternative to IT-BLM.
authors.affiliation: Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Swarna
authors.initials: S
authors.lastname: Bale
authors.affiliation: Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Sunkoju
authors.affiliation: Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Shiva Shankar
authors.initials: SS
authors.lastname: Reddy
authors.affiliation: Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Veerabhadra
authors.initials: V
authors.lastname: Swamy
authors.affiliation: Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Chandraiah
authors.initials: C
authors.lastname: Godugu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D010614:Pharynx / Q000187:drug effects* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D053120:Respiratory Aspiration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D018836:Inflammation Mediators; D001761:Bleomycin
keywords: Bleomycin; oropharyngeal aspiration; pulmonary fibrosis