Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 29, 2025 1 day, 4 hours, 18 minutes ago
Medical News: Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M.tb), is often associated with the lungs. However, approximately 17% of TB cases globally involve other parts of the body, known as extrapulmonary TB (EPTB). Immunocompromised individuals, such as those with HIV or diabetes, are particularly susceptible to this form of Tuberculosis. A new study sheds light on how a vital antioxidant, glutathione (GSH), plays a critical role in controlling EPTB, particularly in the liver and spleen.
Glutathione Depletion Worsens Tuberculosis in Liver and Spleen
Conducted by researchers from the College of Osteopathic Medicine of the Pacific at Western University of Health Sciences, California, and Rutgers University’s Public Health Research Institute in New Jersey, this study utilized a mouse model to uncover how glutathione depletion impacts TB progression. This
Medical News report highlights their key findings and implications.
The Importance of Glutathione in Immune Defense
Glutathione is a natural antioxidant found in cells that protects against harmful oxidative stress caused by reactive oxygen species (ROS). It is especially crucial for immune cells to function properly, aiding in the containment of infections like TB. The study focused on reduced glutathione (rGSH), the active form that fights oxidative damage, and its oxidized counterpart (GSSG), which indicates depletion of protective reserves.
Immunocompromised individuals often exhibit lower GSH levels, leading researchers to hypothesize that this deficiency might worsen TB infections beyond the lungs. Previous studies demonstrated that GSH depletion increases the bacterial burden in the lungs. However, its role in liver and spleen infections, two organs commonly affected by EPTB, had not been explored until now.
The Experiment: How Depletion Worsened TB Outcomes
To test their hypothesis, the researchers used diethyl maleate (DEM), a chemical agent known to deplete GSH levels in cells. They infected two groups of mice with TB bacteria: one group received DEM treatment to induce GSH depletion, while the other group remained untreated. Over eight weeks, the team analyzed GSH levels, bacterial growth, cytokine activity, and tissue damage in the liver and spleen.
Key findings revealed:
-Significant GSH Depletion: Mice treated with DEM experienced a drastic reduction in rGSH levels, especially by the eighth week. This reduction impaired their ability to combat oxidative stress.
-Higher Oxidative Damage: Elevated malondialdehyde (MDA) levels, a marker of cellular damage caused by ROS, were observed in DEM-treated mice.
-Increased TB Burden: The liver and spleen of DEM-treated mice showed a twofold increase in TB bacteria compared to untreated mice. This highlighted how GSH depletion directly facilitated bacterial growth.
-Cytokine
Imbalance: Cytokines, proteins crucial for immune signaling, showed stark imbalances. Key pro-inflammatory cytokines like IL-6 and TNF-α were significantly elevated, while IL-12 and IL-17, which aid in controlling TB, were reduced. This imbalance disrupted the immune response.
-Granuloma Disruption: Granulomas, organized immune cell clusters that contain TB bacteria, were larger but poorly structured in DEM-treated mice. This lack of organization indicated weakened defense mechanisms.
Implications for Immune Function and TB Treatment
These findings emphasize the critical role of GSH in immune regulation. Without adequate GSH, the body fails to mount an effective response against TB bacteria. The cytokine imbalance observed in DEM-treated mice suggests that oxidative stress can derail immune signaling pathways, leading to uncontrolled infection.
Interestingly, the study also highlighted how elevated levels of TGF-β, an immunosuppressive cytokine, contributed to granuloma failure. This suggests that GSH depletion not only weakens the initial immune defense but also promotes conditions favorable for bacterial growth.
Conclusions: Why Redox Balance Matters
This study underscores the importance of maintaining a balance between antioxidants like GSH and oxidative stress for combating infections like TB. The researchers concluded that GSH depletion results in oxidative stress, immune dysfunction, and increased bacterial burden, particularly in the liver and spleen. Their findings pave the way for exploring GSH supplementation or therapies targeting oxidative stress as potential strategies to manage EPTB.
In the words of the researchers, "Maintaining redox homeostasis could enhance immune defense mechanisms, offering hope for better outcomes in TB patients, especially those with underlying conditions like HIV or diabetes."
Final Thoughts and Future Directions
While the study provides valuable insights, the researchers acknowledged some limitations. Mouse models, though useful, do not fully replicate human immune responses. Additionally, the exact sources of cytokines in the study were not identified, leaving room for further research. Future studies could investigate how GSH supplementation impacts TB treatment in humans and explore its role in other extrapulmonary sites.
The study findings were published in the peer-reviewed journal: Biology.
https://www.mdpi.com/2079-7737/14/2/131
Thailand
Medical News would like to highlight that COVID-19 infections depletes glutathione levels in the body as such could cause complications in those with dormant TB infections or those getting exposed to TB.
https://www.thailandmedical.news/news/breaking-study-shows-that-sars-cov-2-infections-lead-to-increased-levels-of-oxidative-stress,-oxidant-damage-and-glutathione-deficiency
https://www.thailandmedical.news/news/covid-19-new-american-researchers-uncover-the-importance-of-selenium-and-glutathione-supplementation-in-covid-19-as-sars-cov-2-mpro-targets-these
For the latest TB News, keep on logging to Thailand
Medical News.
Read Also:
https://www.thailandmedical.news/news/new-strategies-for-combating-tuberculosis-with-repurposed-drugs-and-natural-remedies
https://www.thailandmedical.news/news/restoring-immunity-to-fight-tuberculosis
https://www.thailandmedical.news/articles/tuberculosis-tb-news
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