N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.
N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.
复制标题
DOI：
10.1186/s12866-016-0872-7
复制
发表时间：
2016-10-28
期刊：
影响因子：
4.2
通讯作者：
Andrade BB
中科院分区：
文献类型：
--
作者：
Amaral EP;Conceição EL;Costa DL;Rocha MS;Marinho JM;Cordeiro-Santos M;D'Império-Lima MR;Barbosa T;Sher A;Andrade BB
结核分枝杆菌感染被认为是导致氧化应激的原因。N-乙酰半胱氨酸(NAC)具有粘液溶解和抗氧化活性，被广泛应用于包括肺结核在内的慢性肺部疾病患者。在这里，我们测试了NAC是否对分枝杆菌具有直接的抗生素活性。比较肺结核(PTB)患者、结核分枝杆菌潜伏感染(LTBI)患者和健康对照组血浆氧化应激状态。检测感染结核分枝杆菌的原代人单核巨噬细胞经NAC处理前后的脂质过氧化、DNA氧化和细胞死亡，以及活性氧(ROS)的积累。结核分枝杆菌、禽类分枝杆菌和牛分枝杆菌BCG培养物也被暴露于不同剂量的NAC中，并调节或不调节介质的pH以控制酸度。在结核分枝杆菌感染的人THP-1细胞和缺乏完整功能的NADPH氧化酶系统的小鼠骨髓来源的巨噬细胞中，评估了NAC的抗分枝杆菌作用。在小鼠(C57BL/6)模型上进一步测试了NAC对结核分枝杆菌感染的控制能力。与LTBI患者或未感染的对照组相比，肺结核患者的氧化产物水平升高，抗氧化剂减少。在结核分枝杆菌感染的人巨噬细胞中进行NAC治疗，可以减少由分枝杆菌引起的氧化应激和细胞死亡。重要的是，我们观察到NAC处理的结核分枝杆菌、绵羊分枝杆菌和卡介苗的代谢活性和体外生长均呈剂量依赖性降低。此外，感染巨噬细胞的抗分枝杆菌活性不依赖于NAC对宿主NADPH氧化酶系统的影响。活体内短期NAC治疗结核分枝杆菌感染的小鼠可显著降低肺部的分枝杆菌载量。NAC显示出强大的抗分枝杆菌作用，并可能通过抑制宿主氧化反应和直接抗菌活性来限制结核分枝杆菌的感染和疾病。本文的在线版本(doi：10.1186/s12866-0160872-7)包含补充材料，授权用户可以使用。
Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. NAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity. The online version of this article (doi:10.1186/s12866-016-0872-7) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.7
作者：
Choi SH;Aid S;Kim HW;Jackson SH;Bosetti F
通讯作者：
Bosetti F
影响因子：
3.1
作者：
Fontan, Patricia;Aris, Virginie;Smith, Issar
通讯作者：
Smith, Issar
影响因子：
158.5
作者：
HARRISON, PM;WENDON, JA;WILLIAMS, R
通讯作者：
WILLIAMS, R
DOI：
10.1186/s13046-014-0092-7
发表时间：
2014-11-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Amini A;Masoumi-Moghaddam S;Ehteda A;Morris DL
通讯作者：
Morris DL
影响因子：
9.4
作者：
GOMEZFLORES, R;GUPTA, S;MEHTA, RT
通讯作者：
MEHTA, RT