Glutathione Supplementation Improves Macrophage Functions in HIV

Morris, Devin; Guerra, Carlos; Khurasany, Melissa; Guilford, Frederick T.; Saviola, Beatrice; Huang, Ying; Venketaraman, Vishwanath

doi:10.1089/jir.2012.0103

Cited by 47 publications

(62 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A growing body of evidence suggests that NAC can affect bacterial viability inside of eukaryotic host cells [45]. To test this concept with mycobacteria we infected THP-1 cells (to reduce variability between blood donors) with M. tuberculosis , M. avium or M. bovis BCG bacilli (MOI of 10) for 3 h, replaced the media, and added NAC (10 mM) to half of the cultures.…”

Section: Resultsmentioning

confidence: 99%

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

et al. 2016

View full text Add to dashboard Cite

Background Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria.MethodsOxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model.ResultsPTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs.ConclusionsNAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0872-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It is now known that a number of interactions may occur that prevent the de novo formation of GSH. For example, it has been shown that glutathione is decreased due to an inability to produce glutathione in the extracellular lung fluid of children with chronic asthma [45] and in the macrophages of adults with human immunodeficiency virus (HIV) [46]. …”

Section: Glutathione Sources In the Bodymentioning

confidence: 99%

“…This study demonstrates that without function of the genes needed to produce glutathione supplying the building block of glutathione production, NAC is much less efficient than supplying the whole molecule of glutathione using a liposomal encapsulation of glutathione [46]. …”

Section: Glutathione Sources In the Bodymentioning

confidence: 99%

“…It has been shown that a decrease in glutathione in antigen-presenting cells correlates with increased Th2 response [94,95]. Decreased glutathione found in macrophage cells from children with chronic asthma has been shown to be related to decreased bacterial phagocytosis [96]. In the children with chronic asthma, the decrease in glutathione was shown to be related to post-translational modification of Nrf2, which resulted in decreased gene expression of the enzymes of glutathione production.…”

Section: Mycotoxin Effect On Immunity Is Oxidative Stress Relatedmentioning

confidence: 99%

See 1 more Smart Citation

Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness

Guilford

Hope

2014

Toxins

Self Cite

View full text Add to dashboard Cite

Evidence for the role of oxidative stress in the pathophysiology of mycotoxin-related illness is increasing. The glutathione antioxidant and detoxification systems play a major role in the antioxidant function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that mycotoxins can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress that leads to tissue damage and systemic illness. The review discusses the mechanisms by which mycotoxin-related deficiency of glutathione may lead to both acute and chronic illnesses.

show abstract

“…Additionally, it was shown that this reduction correlated with the decreased levels of intracellular GSH. Furthermore, the same group had shown that the GSH levels in plasma and peripheral blood mononuclear cells of HIV-positive individuals were also compromised [40,41].…”

Section: Gsh Deficiency In Hiv Patientsmentioning

confidence: 99%