drug-induced oxidative stress and toxicity药物引起的氧化应激和毒性.pdfVIP

Hindawi Publishing Corporation Journal of Toxicology Volume 2012, Article ID 645460, 13 pages doi:10.1155/2012/645460 Review Article Drug-Induced Oxidative Stress and Toxicity Damian G. Deavall, Elizabeth A. Martin, Judith M. Horner, and Ruth Roberts Safety Assessment, AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK Correspondence should be addressed to Ruth Roberts, ruth.roberts@ Received 1 March 2012; Revised 26 April 2012; Accepted 29 April 2012 Academic Editor: Y. James Kang Copyright © 2012 Damian G. Deavall et al. 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. Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. 1. Introduction tone and blood pressure, platelet activation, and vascular cell