Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients—A Systematic Review

Mapamba, Daniel; Sauli, Elingarami; Mrema, Lucy Elauteri; Lalashowi, Julieth; Magombola, David; Buza, Joram; Olomi, Willyhelmina; Wallis, Robert S.; Ntinginya, Nyanda Elias

doi:10.3390/antiox11112298

Cited by 7 publications

(5 citation statements)

References 55 publications

(55 reference statements)

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“…N‐acetylcysteine (NAC) is a precursor of GSH synthesis and a direct antioxidant. Clinically, NAC has been successfully used as a treatment for several diseases, such as chronic obstructive pulmonary disease, pediatric mania, and tuberculosis 48 . The current study investigates the effects of ROS in CA‐induced activation of GCN2/eIF2α pathway and FGR.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, NAC has been successfully used as a treatment for several diseases, such as chronic obstructive pulmonary disease, pediatric mania, and tuberculosis. 48 The current study investigates the effects of ROS in CA-induced activation of GCN2/eIF2α pathway and FGR. Our results found that NAC inhibited CA-induced phosphorylation of GCN2 and eIF2α in mouse placentas and human placental trophoblast.…”

Section: Discussionmentioning

confidence: 99%

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Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

Lin

et al. 2023

The FASEB Journal

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Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA).Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11β-Hydroxysteroid dehydrogenase-2 (11β-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11β-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/ eIF2α pathway and subsequent down-regulation of 11β-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding How to cite this article: Lin S, Ye M-Y, Fu Q-Y, et al. Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway. The

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

Lin

et al. 2023

The FASEB Journal

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“…NAC supplementation may restore cellular GSH levels and prevent apoptosis caused by GSH depletion [175]. Appropriate doses of NAC can enhance pulmonary recovery and replenish the GSH levels in patients with respiratory diseases [176]. NAC supplementation can regulate GSH homeostasis, exert antioxidant effects, and improve athletic performance [177].…”

Section: Increase Gsh Levelsmentioning

confidence: 99%

Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation

Chen,

Wang,

Chang

et al. 2024

IJMS

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Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which are harmful to cells at high levels. Oxidative stress caused by ROS accumulation has been associated with an increased risk of cancer, and cardiovascular and liver diseases. Glutathione (GSH) is an abundant cellular antioxidant that is primarily synthesized in the cytoplasm and delivered to the mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within the mitochondria. A long-term imbalance in the ratio of mitochondrial ROS to mGSH can cause cell dysfunction, apoptosis, necroptosis, and ferroptosis, which may lead to disease. This study aimed to review the physiological functions, anabolism, variations in organ tissue accumulation, and delivery of GSH to the mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide (GSSG) ratio, programmed cell death, and ferroptosis. We also discuss diseases caused by mGSH deficiency and related therapeutics.

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“…TB patients are low in vitamins A, C, E, and also selenium and GSH [82,83]. NAC, a GSH precursor, was shown to limit M. tb infection by suppressing the oxidative stress induced by the infection and also having direct antimicrobial activity [84,85]. The direct effect of GSH involves enhancing nitric oxide (NO).…”

Section: Clinical Trials Using Gsh As Adjunct Therapymentioning

confidence: 99%

Glutathione Modulates Efficacious Changes in the Immune Response against Tuberculosis

et al. 2023

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Glutathione (GSH) is an antioxidant in human cells that is utilized to prevent damage occurred by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals. Due to its immunological role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb infection. In fact, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells, specifically, are a major component and are involved in the release of cytokines and activation of macrophages. GSH also serves an important function in macrophages, natural killer cells, and T cells in modulating their activation, their metabolism, proper cytokine release, proper redox activity, and free radical levels. For patients with increased susceptibility, such as those with HIV and type 2 diabetes, the demand for higher GSH levels is increased. GSH acts as an important immunomodulatory antioxidant by stabilizing redox activity, shifting of cytokine profile toward Th1 type response, and enhancing T lymphocytes. This review compiles reports showing the benefits of GSH in improving the immune responses against M. tb infection and the use of GSH as an adjunctive therapy for TB.

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Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients—A Systematic Review

Cited by 7 publications

References 55 publications

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation

Glutathione Modulates Efficacious Changes in the Immune Response against Tuberculosis

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