Wang Xu, Wu Qinghua, Liu Aimei, Anadón Arturo, Rodríguez José-Luis, Martínez-Larrañaga María-Rosa, Yuan Zonghui, Martínez María-Aránzazu
a Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine , Universidad Complutense de Madrid , Madrid , Spain.
b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural University , Wuhan , Hubei , China.
Drug Metab Rev. 2017 Nov;49(4):395-437. doi: 10.1080/03602532.2017.1354014. Epub 2017 Aug 16.
Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.
对乙酰氨基酚（APAP）是世界上治疗剂量下使用最广泛、最受欢迎的非处方止痛和解热药物之一。APAP过量会导致人和动物严重的肝损伤、肝坏死和肾损伤。许多研究表明，氧化应激与APAP相关的各种毒性有关，并且对各种抗氧化剂进行了评估，以研究它们对APAP诱导的肝肾毒性的保护作用。迄今为止，几乎没有综述涉及与氧化应激相关的APAP毒性。本综述更新了过去几十年对APAP治疗导致的活性氧（ROS）、活性氮（RNS）产生以及氧化应激的研究，最终阐述了它们与APAP毒性和代谢的相关性。APAP的代谢涉及多种细胞色素P450酶，可能由此产生氧化应激，本文对这些代谢因素进行了综述。还讨论了基于抗氧化作用的各种化合物对APAP诱导的器官损伤的治疗方法，以进一步了解氧化应激在APAP诱导的毒性中的作用。本综述将为氧化应激在APAP诱导的毒性中的关键作用提供新的见解，以及在理解APAP毒性、器官损伤和细胞信号通路方面仍然存在的矛盾和盲点，最后提供有助于补救此类氧化损伤的策略。
