title: Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters.
abstract: 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,1-alpha-tocopherol acetate/kg chow) to protect against pulmonary damage following intratracheal administration of AM (1.83 micromol) 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.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Card
authors.forename: R G
authors.initials: RG
authors.lastname: Leeder
authors.forename: W J
authors.initials: WJ
authors.lastname: Racz
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: T M
authors.initials: TM
authors.lastname: Bray
authors.forename: T E
authors.initials: TE
authors.lastname: Massey
mesh_terms: D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D019587:Dietary Supplements; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D014677:Pharmaceutical Vehicles; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D014677:Pharmaceutical Vehicles; D014810:Vitamin E; D003094:Collagen; D000638:Amiodarone; D006909:Hydroxyproline