Liposomal Glutathione Supplementation Mitigates Extrapulmonary Tuberculosis in the Liver and Spleen

Sasaninia, Kayvan; Kelley, Melissa; Abnousian, Arbi; Owens, James; Yoon, Seong-Il; Beever, Abrianna; Kachour, Nala; Yegiazaryan, Aram; Kolloli, Afsal; Kumar, Ranjeet; Ramasamy, Santhamani; Subbian, Selvakumar; Venketaraman, Vishwanath

doi:10.31083/j.fbe1503015

Cited by 2 publications

(6 citation statements)

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“…Sasaninia et al. confirmed the favorable controlling effect of L-GSH supplementation in extrapulmonary tuberculosis in mice as well ( 197 ). (L-GSH supplementation has been shown to be an effective adjuvant therapy in both pulmonary TB and extrapulmonary TB).…”

Section: Hdt For Mtb Treatment In Diabetes Mellitus Conditionmentioning

confidence: 89%

Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus

Zhao,

Fan,

Sun

et al. 2024

Front. Immunol.

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Tuberculosis (TB) is caused by the bacterial pathogen Mycobacterium tuberculosis (MTB) and is one of the principal reasons for mortality and morbidity worldwide. Currently, recommended anti-tuberculosis drugs include isoniazid, rifampicin, ethambutol, and pyrazinamide. TB treatment is lengthy and inflicted with severe side-effects, including reduced patient compliance with treatment and promotion of drug-resistant strains. TB is also prone to other concomitant diseases such as diabetes and HIV. These drug-resistant and complex co-morbid characteristics increase the complexity of treating MTB. Host-directed therapy (HDT), which effectively eliminates MTB and minimizes inflammatory tissue damage, primarily by targeting the immune system, is currently an attractive complementary approach. The drugs used for HDT are repositioned drugs in actual clinical practice with relative safety and efficacy assurance. HDT is a potentially effective therapeutic intervention for the treatment of MTB and diabetic MTB, and can compensate for the shortcomings of current TB therapies, including the reduction of drug resistance and modulation of immune response. Here, we summarize the state-of-the-art roles and mechanisms of HDT in immune modulation and treatment of MTB, with a special focus on the role of HDT in diabetic MTB, to emphasize the potential of HDT in controlling MTB infection.

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Section: Hdt For Mtb Treatment In Diabetes Mellitus Conditionmentioning

confidence: 89%

Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus

Zhao,

Fan,

Sun

et al. 2024

Front. Immunol.

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“…ARE controls the enzymes involved in the synthesis and regulation of GSH, including glutamate-cysteine ligase, glutathione-S-transferase (GST), and glutathione synthetase (GS) [ 23 ]. The administration of exogenous L-GSH+RIF has been demonstrated to improve the immune response to M. tb infection in lung tissue [ 24 ]. However, the combined impact of GSH and RIF on liver tissue during an M. tb infection remains unclear in vivo [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…In our most recent study, we investigated the M. tuberculosis burden in the livers of db/db mice infected via the aerosol route [ 24 ]. Compared to untreated M. tuberculosis -infected db/db mice, L-GSH treatment did not significantly reduce M. tuberculosis survival in the liver at 4 weeks post-infection [ 24 ]. However, treatment with RIF led to a large decrease in the number of M. tuberculosis in the liver at 4 weeks post-infection [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Compared to untreated M. tuberculosis -infected db/db mice, L-GSH treatment did not significantly reduce M. tuberculosis survival in the liver at 4 weeks post-infection [ 24 ]. However, treatment with RIF led to a large decrease in the number of M. tuberculosis in the liver at 4 weeks post-infection [ 24 ]. Notably, treatment with a combination of L-GSH and RIF significantly reduced the viability of M. tuberculosis in the liver, with the bacterial burden in the L-GSH+RIF group being even lower than that in the RIF-only group [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, treatment with RIF led to a large decrease in the number of M. tuberculosis in the liver at 4 weeks post-infection [ 24 ]. Notably, treatment with a combination of L-GSH and RIF significantly reduced the viability of M. tuberculosis in the liver, with the bacterial burden in the L-GSH+RIF group being even lower than that in the RIF-only group [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

Badaoui,

Sasaninia,

Mohan

et al. 2024

Biomedicines

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Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections.

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Liposomal Glutathione Supplementation Mitigates Extrapulmonary Tuberculosis in the Liver and Spleen

Cited by 2 publications

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Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus

Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus

Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

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