INSERM, UMRS 1138 Centre de Recherche des Cordeliers Paris France.
INSERM, UMR 991 Université de Rennes 1 Rennes France.
Pharmacol Res Perspect. 2016 Feb 4;4(1):e00211. doi: 10.1002/prp2.211. eCollection 2016 Feb.
Drug-induced toxicity is a key issue for public health because some side effects can be severe and life-threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug-induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug-induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug-induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.
药物毒性是公共卫生的一个关键问题，因为一些副作用可能很严重，甚至危及生命。这些不良反应也是制药公司的主要关注点，因为显著的毒性可能导致临床试验中断，或者有问题的药物从市场上撤出。最近的研究表明，内质网（ER）应激可能是药物不良反应的一个重要事件，除了其他关键机制，如线粒体功能障碍和氧化应激。事实上，药物诱导的 ER 应激会导致细胞和组织内的几种有害影响，包括脂质积累、细胞死亡、细胞溶解和炎症。在回顾了不同病理生理情况下药物不良反应和 ER 应激的重要信息之后，本综述总结了与药物诱导的 ER 应激及其在不同不良反应中的潜在作用相关的主要数据。本文中提到的药物有对乙酰氨基酚（APAP）、三氧化二砷和其他抗癌药物、双氯芬酸以及不同的抗逆转录病毒化合物。我们还包括了关于衣霉素（一种由于毒性而未在人类医学中使用的抗生素）和海帕西琼（地中海植物 Thapsia garganica 的一种有毒化合物）的数据，因为这两种分子通常被用作诱导细胞和动物模型中 ER 应激的典型毒素。
