A Characterization of Amiodarone-Induced Pulmonary Toxicity in F344 Rats and Identification of Surfactant Protein-D as a Potential Biomarker for the Development of the Toxicity

Details

• Personal Author:
  Bowman LL ; Hubbs, Ann F. ; Mason RJ ; Miles PR ; Reasor MJ ; Shannon K ; Taylor MD ; Van Dyke K
• Description:
  Amiodarone (AD) is gaining support as a first-line antiarrhythmic drug despite its potentially fatal pulmonary toxicity involving inflammation and fibrosis. The goals of this study were to characterize a rat model of AD-induced pulmonary toxicity (AIPT) and identify a serum biomarker to aid in the diagnosis of the onset of pulmonary toxicity. Male F344 rats were instilled intratracheally with AD (6.25 mg/kg with a 3.125 mg/ml solution) in sterile water or the sterile water vehicle on days 0 and 2, a protocol that led to the development of pulmonary fibrosis on day 28 in the AD-treated animals. Animals were killed on days 3, 5, 6, 7, or 10 and bronchoalveolar lavage (BAL) was performed. Recovery of alveolar macrophages and eosinophils was increased on days 3 and 5, while neutrophil recovery and albumin levels in the first BAL fraction were significantly elevated only on day 3. BAL cells recovered from AD-treated rats at day 3 produced more phorbol myristate acetate-stimulated luminol-dependent chemiluminescence (LDCL) over 20 min than BAL cells from control rats. Experiments using specific inhibitors implicated superoxide and nitric oxide in at least part of the LDCL response. Serum levels of surfactant protein-D (SP-D), a surfactant-associated protein, were increased concurrently with the inflammatory response in the lungs. These findings indicate that this model exhibits transient pulmonary inflammation and damage, with the potential for elevated oxidant production in the lungs and subsequent pulmonary fibrosis. Also, SP-D is proposed as a specific biomarker to monitor the onset of AIPT in this model. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Fibrosis Hazardous Substances Laboratories Lung Diseases Occupational Health Respiratory Tract Diseases Safety Surface-Active Agents
• Keywords:
  Amiodarone-induced Pulmonary Toxicity Animal Studies Author Keywords: Amiodarone Biomarker Inflammation Laboratory Animals Models Pulmonary System Disorders Respiratory System Disorders Surfactant Protein-D Surfactants Toxic Effects Toxins

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• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  182-190
• Volume:
  167
• Issue:
  3
• NIOSHTIC Number:
  nn:20020830
• Citation:
  Toxicol Appl Pharmacol 2000 Sep; 167(3):182-190
• Contact Point Address:
  Department of Pharmacology and Toxicology, West Virginia University, P.O. Box 0223, Morgantown, WV 26505
• Email:
  mreasor@hsc.wvu.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:569d4328f304384f7f71cbc3729e87af20d60fe7df24d3fd85a22919af9c8b560e3846c52f4f8124560ecd428f68c7975fada6833c2b9a3867fdff6c60dd1c15
• Download URL:
  https://stacks.cdc.gov/view/cdc/198492/cdc_198492_DS1.pdf
• File Type:
  [PDF - 237.76 KB ]