Card J W, Leeder R G, Racz W J, Brien J F, Bray T M, Massey T E
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Toxicology. 1999 Apr 15;133(2-3):75-84. 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,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.
胺碘酮(AM)是一种强效抗心律失常药物,但其不良反应限制了其临床应用,这些不良反应包括可能危及生命的胺碘酮诱发的肺毒性(AIPT)。本研究测试了膳食补充维生素E(500 IU d,1-α-生育酚醋酸酯/千克饲料)对雄性金黄叙利亚仓鼠气管内给予AM(1.83微摩尔)后肺损伤的保护作用。给药后21天,与对照组相比,接受AM治疗的动物肺羟脯氨酸含量和组织病理学疾病指数值增加(P<0.05),这表明存在纤维化。膳食补充维生素E 6周导致给药时肺维生素E含量增加234%,并且持续食用该饮食可防止给药后21天AM诱导的羟脯氨酸含量升高和疾病指数升高。膳食补充维生素E还降低了经蒸馏水(AM的赋形剂)气管内给药的仓鼠的羟脯氨酸含量和疾病指数值。这些结果证明了维生素E在AIPT体内模型中的保护作用,并表明这种抗氧化剂可能在肺中具有非特异性抗纤维化作用。