Subchronic pulmonary inflammation and fibrosis induced by silica in rats are attenuated by amiodarone.
A previous study demonstrated that the acute phase of silica-induced lung injury in rats can be attenuated by concomitant administration of amiodarone, a cationic amphiphilic drug that inhibits phospholipase activity in the lungs. The purpose of the present study was to determine whether continued amiodarone administration could inhibit subchronic silica-induced lung injury and fibrosis. Male Fischer-344 rats were administered amiodarone (150 mg/kg, p.o., 5 days/week) for 14 days and were then instilled with silica (100 mg/kg) intratracheally. Amiodarone treatment then continued for 60 days. Injury was evaluated by parameters in bronchoalveolar lavage fluid and fibrosis was assessed by lung hydroxyproline content and trichrome staining of collagen. Within the bronchoalveolar lavage fluid, amiodarone treatment resulted in significant decreases in silica-induced elevations in albumin levels, lactate dehydrogenase activity, beta-glucuronidase activity, and neutrophil influx. Amiodarone treatment resulted in significant reductions in silica-induced increases in lung weight and hydroxyproline levels; the diminution of fibrosis due to amiodarone treatment was confirmed histologically. These results indicate that subchronic pulmonary inflammation and fibrosis induced by silica in the rat can be attenuated by the concomitant administration of amiodarone.
Blake
T L
TL
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506-9223, USA.
DiMatteo
M
M
Antonini
J M
JM
McCloud
C M
CM
Reasor
M J
MJ
D000418:Albumins / Q000032:analysis / Q000187:drug effects; D000638:Amiodarone / Q000031:analogs & derivatives / Q000032:analysis / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005966:Glucuronidase / Q000187:drug effects / Q000378:metabolism; D006099:Granuloma / Q000473:pathology; D015614:Histiocytosis / Q000473:pathology; D006909:Hydroxyproline / Q000032:analysis; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D012107:Research Design; D012822:Silicon Dioxide; D012829:Silicosis / Q000188:drug therapy* / Q000473:pathology
D000418:Albumins; D004791:Enzyme Inhibitors; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; C036116:desethylamiodarone; D000638:Amiodarone; D006909:Hydroxyproline