Liposomal Glutathione Supplementation Mitigates Extrapulmonary Tuberculosis in the Liver and Spleen

• Published in: Frontiers in bioscience (Elite edition) Vol. 15; no. 3; p. 15
• Main Authors: Sasaninia, Kayvan, Kelley, Melissa, Abnousian, Arbi, Owens, James, Yoon, SonYeol, Beever, Abrianna, Kachour, Nala, Yegiazaryan, Aram, Kolloli, Afsal, Kumar, Ranjeet, Ramasamy, Santhamani, Subbian, Selvakumar, Venketaraman, Vishwanath
• Format: Journal Article
• Language: English
• Published: IMR Press 06.07.2023
• Subjects: extrapulmonary tuberculosis; glutathione; liver; mycobacterium tuberculosis; oxidative stress; spleen; tuberculosis
• ISSN: 1945-0494; 1945-0508; 1944-7892
• DOI: 10.31083/j.fbe1503015

BACKGROUNDExtrapulmonary 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. METHODSIn 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. RESULTSL-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. CONCLUSIONSOverall, 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.