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Mediators of Inflammation
Volume 2 (1993), Issue 4, Pages 279-285
http://dx.doi.org/10.1155/S0962935193000389

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

1Departments of Veterinary Pharmacology and Toxicology, University of California, Davis, CA 95616, USA
2Departments of Anatomy and Cell Biology School of Veterinary Medicine, University of California, Davis, CA 95616, USA

Received 11 March 1993; Accepted 28 April 1993

Copyright © 1993 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Therapeutic use of amiodarone (AMD), a Class III antiarrhythmic drug is complicated by the development of lung fibrosis (LF) and phospholipidosis (PL). In the present study, the effectiveness of a PAF antagonist, WEB 2086, against AMD induced LF and PL has been tested in hamsters. The animals were randomly divided into four groups: (1) saline + H2O; (2) WEB + H2O; (3) saline + AMD; and (4) WEB + AMD. Saline or WEB (10 mg/kg i.p.) was given 2 days prior to intratracheal instillation of water or AMD (1.5 μmol/0.25 ml/100 g BW) and thereafter daily throughout the study. Twenty-eight days after intratracheal instillation, the animals were killed and the lungs processed for various assays. The amount of lung hydroxyproline, an index of LF, in saline + H2O, WEB + H2O, saline + AMD, and WEB + AMD groups were 959 ± 46, 1035 ± 51, 1605 ± 85 and 1374 ± 69 μg/lung, respectively. Total lung PL, an index of phospholipidosis, in the corresponding groups were 8.4 ± 0.4, 8.3 ± 0.3, 11.7 ± 0.3 and 9.9 μg/lung. Lung malondialdehyde, an index of lipid peroxidation and superoxide dismutase activity in saline + H2O WEB + H2O, saline + AMD, and WEB + AMD were 93.0 ± 4.3, 93.0 ± 2.7, 138.9 ± 6.0 and 109.0 ± 3.8 nmol/lung and 359.7 ± 13.9, 394.0 ± 22.8, 497.5 ± 19.7 and 425.5 ± 4.9 units/lung, respectively. Administration of AMD alone caused significant increases in all the above indexes of lung toxicity, and treatment with WEB 2086 minimized the AMD induced toxicity as reflected by significant decreases in these indexes. Histopathological studies revealed a marked reduction in the extent and severity of lung lesions in the WEB + AMD group compared with the saline + AMD group. Treatment with WEB 2086 also reduced the acute mortality from 35% in saline + AMD group to 22% in WEB + AMD group. It was concluded that PAF is involved in the AMD induced lung fibrosis and phospholipidosis and that the PAF receptor antagonist may, therefore, be potentially useful in reducing AMD induced lung toxicity.