Rationale for the use ofN-acetylcysteine in both prevention and adjuvant therapy of COVID-19
Rationale for the use ofN-acetylcysteine in both prevention and adjuvant therapy of COVID-19
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DOI：
10.1096/fj.202001807
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发表时间：
2020-08-11
期刊：
影响因子：
4.8
通讯作者：
La Maestra, Sebastiano
中科院分区：
文献类型：
--
作者：
De Flora, Silvio;Balansky, Roumen;La Maestra, Sebastiano
COVID-19可能导致肺炎、急性呼吸窘迫综合征、心血管改变和多器官衰竭，这些都被归因于细胞因子风暴、全身炎症反应和免疫系统的攻击。此外，已证明COVID-19患者会出现氧化应激失衡。N-乙酰基-L-半胱氨酸（NAC）是还原型谷胱甘肽（GSH）的前体。由于其耐受性，这种多效性药物不仅被提议作为粘液溶解剂，而且还被提议作为涉及GSH耗竭和氧化应激的各种疾病的预防/治疗剂。在非常高的剂量下，NAC也被用作对抗扑热息痛中毒的解毒剂。巯基阻断血管紧张素转换酶2，从而阻碍SARS-CoV-2渗透到细胞中。基于本文综述的广泛的抗氧化和抗炎机制，NAC的口服给药可能会降低发生COVID-19的风险，因为它以前被证明用于流感和流感样疾病。此外，高剂量静脉注射NAC有望在治疗严重COVID-19病例和控制其致命并发症（也包括肺和心血管不良事件）方面发挥辅助作用。
COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients.N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.