Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters

• Published in: Toxicology (Amsterdam) Vol. 133; no. 2; pp. 75 - 84
• Main Authors: Card, Jeffrey W., Leeder, Randall G., Racz, William J., Brien, James F., Bray, Tammy M., Massey, Thomas E.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.04.1999; Amsterdam Elsevier Science
• Subjects: Amiodarone; Amiodarone - toxicity; Animals; Anti-Arrhythmia Agents - toxicity; Biological and medical sciences; Collagen - metabolism; Cricetinae; Dietary supplementation; Dietary Supplements; Drug toxicity and drugs side effects treatment; Fibrosis; Hydroxyproline - metabolism; Lung; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Medical sciences; Mesocricetus; Organ Size - drug effects; Pharmaceutical Vehicles; Pharmacology. Drug treatments; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - prevention & control; Pulmonary toxicity; Toxicity: respiratory system, ent, stomatology; Vitamin E; Vitamin E - therapeutic use; Amiodarone; Dietary supplementation; Vitamin E; Pulmonary toxicity; Lung; Fibrosis; Lung disease; Respiratory disease; Toxicity; Rodentia; E-Vitamins; Antiarrhythmic agent; Antioxidant; Iodine Organic compounds; Prevention; Vertebrata; Chemotherapy; Mammalia; Animal; Interstitial pneumonitis; Supplementation; Hamster
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(99)00009-8

Amiodarone (AM) is a potent antidysrhythmic agent that is limited in clinical use by its adverse effects, including potentially life-threatening AM-induced pulmonary toxicity (AIPT). The present study tested the ability of dietary supplementation with vitamin E (500 IU d,l-α-tocopherol acetate/kg chow) to protect against pulmonary damage following intratracheal administration of AM (1.83 μmol) to the male golden Syrian hamster. At 21 days post-dosing, animals treated with AM had increased lung hydroxyproline content and histological disease index values compared to control ( P<0.05), which were indicative of fibrosis. Dietary vitamin E supplementation for 6 weeks resulted in a 234% increase in lung vitamin E content at the time of AM dosing, and maintenance on the diet prevented AM-induced elevation of hydroxyproline content and disease index 21 days post-dosing. Dietary vitamin E supplementation also decreased hydroxyproline content and disease index values in hamsters treated intratracheally with distilled water, the AM vehicle. These results demonstrate a protective role for vitamin E in an in vivo model of AIPT, and suggest that this antioxidant may have non-specific antifibrotic effects in the lung.