异肺结核病（EPTB）占全球结核分枝杆菌感染（M. tb）的五分之一。随着M. tb多药耐药性的上升以及抗生素引起的肝毒性，治疗和管理结核病（TB）面临挑战，因而需要新的治疗方法。以前的研究表明，给予脂质体型谷胱甘肽（L-GSH）可以降低氧化应激，增强肉芽肿反应，并减轻M. tb在M. tb感染的小鼠肺部的负担。然而，尚未探索L-GSH补充在活动性EPTB期间对肝脏和脾脏的影响。 在本研究中，我们评估了未经治疗和经L-GSH处理的M. tb感染的野生型（WT）小鼠的肝脏谷胱甘肽（GSH）和丙二醛（MDA）水平，以及细胞因子谱。此外，还评估了肝脏和脾脏中的M. tb负荷和组织病理学。 L-GSH补充增加了肝脏总GSH水平，并降低了GSH。经L-GSH治疗后，还观察到MDA、氧化GSH和白细胞介素（IL）-6水平的降低。此外，L-GSH补充观察到增加干扰素-γ（IFN-γ）和肿瘤坏死因子（TNF）-α的产生，并降低了IL-10水平。经L-GSH补充后，M. tb在肝脏和脾脏中的存活显著降低。L-GSH治疗还在M. tb感染小鼠的肝脏和脾脏中提供了一种保护宿主的效果。 总的来说，L-GSH补充提高了肝脏中总GSH和还原型GSH的水平，并通过降低氧化应激、增强免疫支持型细胞因子产生和降低免疫抑制型细胞因子水平来减轻M. tb的负荷。这些观察到的益处突显了L-GSH补充在活动性EPTB期间的潜力，并为针对M. tb感染的创新治疗干预提供了见解。©2023 IMR Press发表。

Extrapulmonary tuberculosis (EPTB) accounts for a fifth of all Mycobacterium tuberculosis (M. tb) infections worldwide. The rise of multidrug resistance in M. tb alongside the hepatotoxicity associated with antibiotics presents challenges in managing and treating tuberculosis (TB), thereby prompting a need for new therapeutic approaches. Administration of liposomal glutathione (L-GSH) has previously been shown to lower oxidative stress, enhance a granulomatous response, and reduce the burden of M. tb in the lungs of M. tb-infected mice. However, the effects of L-GSH supplementation during active EPTB in the liver and spleen have yet to be explored.In this study, we evaluated hepatic glutathione (GSH) and malondialdehyde (MDA) levels, and the cytokine profiles of untreated and L-GSH-treated M. tb-infected wild type (WT) mice. Additionally, the hepatic and splenic M. tb burdens and tissue pathologies were also assessed.L-GSH supplementation increased total hepatic levels and reduced GSH. A decrease in the levels of MDA, oxidized GSH, and interleukin (IL)-6 was also detected following L-GSH treatment. Furthermore, L-GSH supplementation was observed to increase interferon-gamma (IFN-γ) and tumor necrosis factor (TNF)-α production and decrease IL-10 levels. M. tb survival was significantly reduced in the liver and spleen following L-GSH supplementation. L-GSH treatment also provided a host-protective effect in the liver and spleen of M. tb-infected mice.Overall, L-GSH supplementation elevated the levels of total and reduced forms of GSH in the liver and reduced the burden of M. tb by decreasing oxidative stress, enhancing the production of immunosupportive cytokines, and reducing the levels of immunosuppressive cytokines. These observed benefits highlight the potential of L-GSH supplementation during active EPTB and provide insight into novel therapeutic interventions against M. tb infections.© 2023 The Author(s). Published by IMR Press.