Beever Abrianna, Kachour Nala, Owens James, Sasaninia Kayvan, Kolloli Afsal, Kumar Ranjeet, Ramasamy Santhamani, Sisliyan Christina, Khamas Wael, Subbian Selvakumar, Venketaraman Vishwanath
Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States.
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
Front Pharmacol. 2022 Jun 24;13:879729. doi: 10.3389/fphar.2022.879729. eCollection 2022.
Both active tuberculosis (TB) and asymptomatic latent () infection (LTBI) cause significant health burdens to humans worldwide. Individuals with immunocompromising health conditions, such as Type 2 Diabetes Mellitus (T2DM), have a weakened ability to control infection and are more susceptible to reactivation of LTBI to active diseases. T2DM cases are known to have glutathione (GSH) deficiency and impaired immune cell function, including the granulomatous response to infection. We have previously reported that liposomal glutathione (L-GSH) supplementation can restore the immune cell effector responses of T2DM cases. However, the effects of L-GSH supplementation on the bactericidal activities of first-line anti-TB drug rifampicin (RIF) against infection have yet to be explored. The aim of this study is to elucidate the effects of L-GSH supplementation in conjunction with RIF treatment during an active infection in a diabetic mouse model. In this study, we evaluated total and reduced levels of GSH, cytokine profiles, malondialdehyde (MDA) levels, burden, and granulomatous response in the lungs. We show that L-GSH supplementation caused a significant reduction in burden in the lungs, decreased oxidative stress, and increased the production of IFN-γ, TNF-α, IL-17, IL-10, and TGF-β1compared to the untreated mice. In addition, L-GSH supplementation in conjunction with RIF treatment achieved better control of infection in the lungs and significantly reduced the levels of oxidative stress compared to treatment with RIF alone. Moreover, L-GSH in conjunction with RIF significantly increased TGF-β1 levels compared to treatment with RIF alone. These findings suggest potential therapeutic benefits of L-GSH supplementation in conjunction with first-line antibiotic therapy against infection in individuals with T2DM.
活动性肺结核（TB）和无症状潜伏性结核感染（LTBI）均给全球人类带来了沉重的健康负担。患有免疫功能低下健康状况的个体，如2型糖尿病（T2DM）患者，控制结核感染的能力减弱，更容易将LTBI重新激活为活动性疾病。已知T2DM患者存在谷胱甘肽（GSH）缺乏和免疫细胞功能受损的情况，包括对结核感染的肉芽肿反应受损。我们之前报道过，补充脂质体谷胱甘肽（L-GSH）可以恢复T2DM患者免疫细胞的效应反应。然而，补充L-GSH对一线抗结核药物利福平（RIF）针对结核感染的杀菌活性的影响尚未得到探索。本研究的目的是阐明在糖尿病小鼠模型的活动性结核感染期间，补充L-GSH联合RIF治疗的效果。在本研究中，我们评估了肺组织中GSH的总量和还原水平、细胞因子谱、丙二醛（MDA）水平、结核负担和肉芽肿反应。我们发现，与未治疗的小鼠相比，补充L-GSH可显著降低肺组织中的结核负担，降低氧化应激，并增加IFN-γ、TNF-α、IL-17、IL-10和TGF-β1的产生。此外，与单独使用RIF治疗相比，补充L-GSH联合RIF治疗能更好地控制肺部的结核感染，并显著降低氧化应激水平。而且，与单独使用RIF治疗相比，L-GSH联合RIF可显著提高TGF-β1水平。这些发现表明，补充L-GSH联合一线抗生素治疗对T2DM个体的结核感染具有潜在的治疗益处。
