N-acetylcysteine, reactive oxygen species and beyond

Sun, Shi‐Yong

doi:10.4161/cbt.9.2.10583

Cited by 247 publications

(173 citation statements)

References 17 publications

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“…The NAC is a known antioxidant that has been found to scavenge ROS in a variety of different cell types in vivo and in vitro. 26 As expected, we found that the cotreatment of the HEK293 cells with NAC significantly reduced the DCFassociated cellular fluorescence. The mechanism by which is not yet understood, but it may result from exchange interactions between the unpaired electrons of free radicals and the conduction band electrons of the nanoparticles, similar to that seen with single-wall carbon nanotubes, semiconductor quantum dots, TiO 2 nanoparticles, and cerium oxide nanoparticles.…”

Section: Discussionsupporting

confidence: 85%

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Selvaraj¹,

Bodapati²,

Murray³

et al. 2014

IJN

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Background The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0–50 μg/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y 2 O 3 ) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant. Results The 24-hour inhibitory concentration 50 (IC 50 ) of Y 2 O 3 NPs (41±5 nm in size) in the HEK293 cells was found to be 108 μg/mL. Incubation with Y 2 O 3 NPs (12.25–50 μg/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response. Conclusion These data demonstrate that the Y 2 O 3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells.

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Section: Discussionsupporting

confidence: 85%

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Selvaraj¹,

Bodapati²,

Murray³

et al. 2014

IJN

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show abstract

“…The antioxidant activity of NAC was accomplished through preventing the formation of ROS and also by scavenging ROS once formed. 16 Our findings confirmed the previous studies indicating that NAC treatment impairs the chemotaxis and ROS production in human phagocytic cells and early TLR4 activation, which is an ROS-dependent event. 17,18 A previous study by Wang and associates showed that NAC can prevent hepatic IRI-induced autophagy and apoptosis by influencing the Janus kinase signaling pathway.…”

Section: Discussionsupporting

confidence: 92%

Evaluating mRNA Expression Levels of the TLR4/IRF5 Signaling Axis During Hepatic Ischemia-Reperfusion Injuries

Nasiri

Saadat²,

Karimi³

et al. 2017

Exp Clin Transplant

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Objectives: Hepatic ischemia and reperfusion during liver transplant surgery result in hepatocellular damage. Toll-like receptors, especially TLR4, have a fundamental basic role in the inflammatory phase of ischemia-reperfusion injuries. The effect of the TRIFdependent signaling pathway downstream of TLR4 in hepatic ischemia-reperfusion injury has been well established. However, the role of TLR4-MyD88-dependent signal transduction in hepatic ischemiareperfusion injury has not yet been clarified. The interferon regulatory factor 5 was introduced as the main regulator of the TLR4-MyD88 signaling pathway for activating proinflammatory cytokines. The present study was carried out to investigate the functional impact of the TLR4/IRF5 signaling axis in hepatic ischemia-reperfusion injury. Materials and Methods: mRNA expression levels of TLR4, IRF5, tumor necrosis factor α, interleukin 1β, and interleukin 6 were measured using real-time polymerase chain reaction after short (3 h) and long (168 h) reperfusion periods in a hepatic mouse model of ischemia-reperfusion injury in the presence and absence of N-acetylcysteine. Liver damage was evaluated by plasma levels of alanine aminotransferase and histopathology. Results: Our results show that mRNA levels of TLR4/IRF5 and its downstream cytokines were significantly elevated 3 hours after reperfusion and had drastically fallen to baseline levels 168 hours after reperfusion. Plasma levels of alanine aminotransferase showed the same pattern. Histopathologic study of the samples revealed significant hepatic cell infiltration and necrosis 168 hours after reperfusion. Pretreatment with N-acetylcysteine significantly decreased the mRNA levels of TLR4/IRF5 and its downstream cytokines 3 hours after reperfusion and subsequently improved the previously mentioned hepatic damages 168 hours after reperfusion. Conclusions: This study suggests a possible role for the TLR4/IRF5 signaling pathway in hepatic ischemiareperfusion injury. Furthermore, it reveals that Nacetylcysteine may suppress this inflammatory axis and consequently improve hepatic injuries.

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“…The NAC that was used in our studies is a commonly used direct ROS scavenger that also acts indirectly to quench ROS by inducing expression of glutathione (81)(82)(83). Nevertheless, some studies have found that NAC can cause effects in cells not related to ROS quenching, as a consequence of its reductive capacity and direct interaction with target proteins to modify their activities (84). Future studies should clarify the role of ROS in enhanced cytokine production in Irgm1-deficient macrophages.…”

Section: Discussionmentioning

confidence: 97%

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

Schmidt

Fee

Henry

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillThe immunity-related GTPases (IRGs) are a family of proteins that are induced by interferon (IFN)-␥ and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes and promote remodeling and trafficking of those membranes. Prior studies have shown that loss of Irgm1 in mice leads to increased lethality to bacterial infections as well as enhanced inflammation to non-infectious stimuli; however, the mechanisms underlying these phenotypes are unclear. In the studies reported here, we found that uninfected Irgm1-deficient mice displayed high levels of serum cytokines typifying profound autoinflammation. Similar increases in cytokine production were also seen in cultured, IFN-␥-primed macrophages that lacked Irgm1. A series of metabolic studies indicated that the enhanced cytokine production was associated with marked metabolic changes in the Irgm1-deficient macrophages, including increased glycolysis and an accumulation of long chain acylcarnitines. Cells were exposed to the glycolytic inhibitor, 2-deoxyglucose, or fatty acid synthase inhibitors to perturb the metabolic alterations, which resulted in dampening of the excessive cytokine production. These results suggest that Irgm1 deficiency drives metabolic dysfunction in macrophages in a manner that is cell-autonomous and independent of infectious triggers. This may be a significant contributor to excessive inflammation seen in Irgm1-deficient mice in different contexts.

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N-acetylcysteine, reactive oxygen species and beyond

Cited by 247 publications

References 17 publications

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Evaluating mRNA Expression Levels of the TLR4/IRF5 Signaling Axis During Hepatic Ischemia-Reperfusion Injuries

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

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