N-Acetylcysteine (NAC) is most commonly used for the treatment of acetaminophen overdose and acetaminophen-induced liver injury. In patients infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), NAC is given to treat hepatotoxicity induced by TB drugs. We had previously shown that cysteine, a derivative of NAC, potentiated the activity of isoniazid, a first-line TB drug, by preventing the emergence of INH resistance and persistence in M. tuberculosis in vitro. Here, we demonstrate that, in vitro, NAC has the same boosting activity with various combinations of first- and second-line TB drugs against drug-susceptible and multidrug-resistant M. tuberculosis strains. Similar to cysteine, NAC increased M. tuberculosis respiration. However, in M. tuberculosis-infected mice, the addition of NAC did not augment the activity of first- or second-line TB drugs. A comparison of the activity of NAC combined with TB drugs in murine and human macrophage cell lines revealed that studies in mice might not be recapitulated during host infection in vivo.

中文翻译：

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N-乙酰半胱氨酸作为一线和二线结核病药物增效剂的前景和局限性

N-乙酰半胱氨酸 (NAC) 最常用于治疗对乙酰氨基酚过量和对乙酰氨基酚诱导的肝损伤。在感染结核分枝杆菌（结核病 (TB) 的病原体）的患者中，给予 NAC 以治疗由结核病药物引起的肝毒性。我们之前已经表明，NAC 的衍生物半胱氨酸通过在体外防止结核分枝杆菌中异烟肼耐药性和持久性的出现，增强了一线结核病 药物异烟肼的活性。在这里，我们证明，在体外，NAC 与一线和二线结核病药物的各种组合对药物敏感和多重耐药结核分枝杆菌具有相同的增强活性菌株。与半胱氨酸类似，NAC 增加了结核分枝杆菌的呼吸作用。然而，在结核分枝杆菌感染的小鼠中，添加 NAC 并未增强一线或二线结核病药物的活性。NAC 与 TB 药物在小鼠和人类巨噬细胞系中的活性比较表明，在体内宿主感染期间，小鼠研究可能无法重现。