Surfactant protein-D as a possible serum biomarker for amiodarone-induced pulmonary toxicity in a rat model.
Reasor-MJ; Taylor-MD; Miles-PR; Shannon-K; Mason-RJ
Am J Respir Crit Care Med 1999 Jan; 159(3)(Suppl):A393
Amiodarone (AD), an important antiarrhythmic drug, can induce pulmonary toxicity characterized by alveolar and interstitial inflammation and subsequent fibrosis. To date, no biomarkers have been identified to allow monitoring of the onset and/or progression of amiodarone-induced pulmonary toxicity (AIPT). Animal models of AIPT have been developed to study the disorder in the laboratory. In the present study, we utilized a rat model of AIPT where AD was instilled intratracheally (i.t.) (6.25 mg/kg in sterile water) on days 0 and 2. Controls received the water vehicle. On day 28, the level of right lung hydroxyproline, a biochemical marker for fibrosis was significantly elevated compared to controls indicating that pulmonary fibrosis had developed. Analysis of bronchoalveolar lavage fluid revealed a variable neutrophilic and strong eosinophilic inflammation through day 7. Surfactant protein-D (SP-D) was significantly elevated 2 to 3-fold in serum from AD-treated compared to control rats on days 5, 6 & 7 of the study. Dosing protocols where fibrosis did not develop (i.e., a single i.t. instillation of AD or when AD was given orally) did not result in an elevation of serum SP-D. The results of this study indicate that SP-D may serve as a serum biomarker to monitor the onset of AIPT.
Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis; Respiratory-system-disorders; Epidemiology; Biomarkers; Biological-factors
American Journal of Respiratory and Critical Care Medicine