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

被引:24
作者
Card, JW
Leeder, RG
Racz, WJ
Brien, JF
Bray, TM
Massey, TE [1 ]
机构
[1] Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada
[2] Leo Labs Canada Ltd, Ajax, ON K7L 3N6, Canada
[3] Ohio State Univ, Dept Human Nutr & Food Management, Columbus, OH 43210 USA
[4] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada
基金
英国医学研究理事会;
关键词
amiodarone; lung; fibrosis; pulmonary toxicity; vitamin E; dietary supplementation;
D O I
10.1016/S0300-483X(99)00009-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu mol) 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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:75 / 84
页数:10
相关论文
共 50 条
[1]   AMIODARONE-INDUCED PNEUMONITIS - ASSESSMENT OF RISK-FACTORS AND POSSIBLE RISK REDUCTION [J].
ADAMS, GD ;
KEHOE, R ;
LESCH, M ;
GLASSROTH, J .
CHEST, 1988, 93 (02) :254-263
[2]   SAFETY OF ORAL INTAKE OF VITAMIN-E [J].
BENDICH, A ;
MACHLIN, LJ .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1988, 48 (03) :612-619
[3]   PULMONARY RESPONSES TO AMIODARONE IN HAMSTERS - COMPARISON OF INTRATRACHEAL AND ORAL ADMINISTRATIONS [J].
BLAKE, TL ;
REASOR, MJ .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1995, 131 (02) :325-331
[4]  
BOLT MW, 1999, TOXICOLOGIST, V48, P128
[5]   IS VITAMIN-E THE ONLY LIPID-SOLUBLE, CHAIN-BREAKING ANTIOXIDANT IN HUMAN-BLOOD PLASMA AND ERYTHROCYTE-MEMBRANES [J].
BURTON, GW ;
JOYCE, A ;
INGOLD, KU .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1983, 221 (01) :281-290
[6]   AMIODARONE-INDUCED PULMONARY FIBROSIS IN HAMSTERS [J].
CANTOR, JO ;
OSMAN, M ;
CERRETA, JM ;
SUAREZ, R ;
MANDL, I ;
TURINO, GM .
EXPERIMENTAL LUNG RESEARCH, 1984, 6 (01) :1-10
[7]  
CHOW CK, 1991, FREE RADICAL BIO MED, V11, P215
[8]   PULMONARY FIBROSIS INDUCED IN THE HAMSTER BY AMIODARONE AND DESETHYLAMIODARONE [J].
DANIELS, JM ;
BRIEN, JF ;
MASSEY, TE .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1989, 100 (02) :350-359
[9]  
Diplock A T, 1982, Acta Vitaminol Enzymol, V4, P303
[10]   CURRENT APPROACHES TO THE THERAPY OF FIBROTIC DISEASES [J].
FRANKLIN, TJ .
BIOCHEMICAL PHARMACOLOGY, 1995, 49 (03) :267-273