Simultaneous Modulation of NLRP3 Inflammasome and Nrf2/ARE Pathway Rescues Thioacetamide-Induced Hepatic Damage in Mice: Role of Oxidative Stress and Inflammation

Inflammation ◽  
2021 ◽  
Author(s):  
Durgesh Kumar Dwivedi ◽  
G. B. Jena
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Hepatic Damage

scholarly journals Metformin Corrects Glucose Metabolism Reprogramming and NLRP3 Inflammasome-Induced Pyroptosis via Inhibiting the TLR4/NF-κB/PFKFB3 Signaling in Trophoblasts: Implication for a Potential Therapy of Preeclampsia

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yang Zhang ◽  
Weifang Liu ◽  
Yanqi Zhong ◽  
Qi Li ◽  
Mengying Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Metabolic Phenotypes ◽  
Pyrin Domain ◽  
Underlying Mechanisms ◽  
And Oxidative Stress ◽  
Receptor Family

NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated pyroptosis is a crucial event in the preeclamptic pathogenesis, tightly linked with the uteroplacental TLR4/NF-κB signaling. Trophoblastic glycometabolism reprogramming has now been noticed in the preeclampsia pathogenesis, plausibly modulated by the TLR4/NF-κB signaling as well. Intriguingly, cellular pyroptosis and metabolic phenotypes may be inextricably linked and interacted. Metformin (MET), a widely accepted NF-κB signaling inhibitor, may have therapeutic potential in preeclampsia while the underlying mechanisms remain unclear. Herein, we investigated the role of MET on trophoblastic pyroptosis and its relevant metabolism reprogramming. The safety of pharmacologic MET concentration to trophoblasts was verified at first, which had no adverse effects on trophoblastic viability. Pharmacological MET concentration suppressed NLRP3 inflammasome-induced pyroptosis partly through inhibiting the TLR4/NF-κB signaling in preeclamptic trophoblast models induced via low-dose lipopolysaccharide. Besides, MET corrected the glycometabolic reprogramming and oxidative stress partly via suppressing the TLR4/NF-κB signaling and blocking transcription factor NF-κB1 binding on the promoter PFKFB3, a potent glycolytic accelerator. Furthermore, PFKFB3 can also enhance the NF-κB signaling, reduce NLRP3 ubiquitination, and aggravate pyroptosis. However, MET suppressed pyroptosis partly via inhibiting PFKFB3 as well. These results provided that the TLR4/NF-κB/PFKFB3 pathway may be a novel link between metabolism reprogramming and NLRP3 inflammasome-induced pyroptosis in trophoblasts. Further, MET alleviates the NLRP3 inflammasome-induced pyroptosis, which partly relies on the regulation of TLR4/NF-κB/PFKFB3-dependent glycometabolism reprogramming and redox disorders. Hence, our results provide novel insights into the pathogenesis of preeclampsia and propose MET as a potential therapy.

scholarly journals NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Merry W. Ma ◽  
Jing Wang ◽  
Krishnan M. Dhandapani ◽  
Darrell W. Brann
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nadph Oxidase ◽  
Nlrp3 Inflammasome ◽  
Healing Process ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Nadph Oxidase 2

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. After the initial primary mechanical injury, a complex secondary injury cascade involving oxidative stress and neuroinflammation follows, which may exacerbate the injury and complicate the healing process. NADPH oxidase 2 (NOX2) is a major contributor to oxidative stress in TBI pathology, and inhibition of NOX2 is neuroprotective. The NLRP3 inflammasome can become activated in response to oxidative stress, but little is known about the role of NOX2 in regulating NLRP3 inflammasome activation following TBI. In this study, we utilized NOX2 knockout mice to study the role of NOX2 in mediating NLRP3 inflammasome expression and activation following a controlled cortical impact. Expression of NLRP3 inflammasome components NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC), as well as its downstream products cleaved caspase-1 and interleukin-1β (IL-1β), was robustly increased in the injured cerebral cortex following TBI. Deletion of NOX2 attenuated the expression, assembly, and activity of the NLRP3 inflammasome via a mechanism that was associated with TXNIP, a sensor of oxidative stress. The results support the notion that NOX2-dependent inflammasome activation contributes to TBI pathology.

Plantamajoside Ameliorates Inflammatory Response of Chondrocytes via Regulating NF-κB/NLRP3 Inflammasome Pathway

2021 ◽  
Vol 11 (5) ◽  
pp. 997-1002
Author(s):  
Chi Zhang ◽  
Yuanhe Wang ◽  
Chuan Hu ◽  
Kang Sun ◽  
Dingzhu Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cell Viability ◽  
Nlrp3 Inflammasome ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apoptotic Cells ◽  
Protein Levels

The damage of articular cartilage in osteoarthritis involves the oxidative stress and inflammation. The aim of the present study was to explore the role of plantamajoside (PM) in chondrocytes and elucidate the underlying mechanism. The cell viability following treatment with PM or lipopolysac-charide (LPS) was assessed by cell counting kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was supplied to determine the levels of pro-inflammatory cytokines. Moreover, the oxidative stress-related markers were evaluated via assay kits. TUNEL assay was employed to stain the apoptotic cells. The components of nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome were estimated by western blot analysis. LPS-insulted cell viability of ATDC5 was restored by PM. PM alleviated the inflammatory response and oxidative stress of ATDC5 cells induced by LPS. Furthermore, it was found that the apoptotic cells were reduced following PM treatment. The protein levels of NF-κB, IκB kinase β (IKKβ) and NLRP3 inflammasome were decreased by PM. These results suggested that PM protected the ATDC5 cells from LPS stimulation, alleviated the inflammatory response may through regulating the NF-κB and NLRP3 inflammasome.

Activation of NLRP3 inflammasome in hepatocytes after exposure to cobalt nanoparticles: The role of oxidative stress

2020 ◽  
Vol 69 ◽  
pp. 104967 ◽  
Author(s):  
Sisi Feng ◽  
Zhenyu Zhang ◽  
Yiqing Mo ◽  
Ruirui Tong ◽  
Zexiang Zhong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Cobalt Nanoparticles

scholarly journals NLRP3 inflammasome mediates oxidative stress-induced pancreatic islet dysfunction

2018 ◽  
Vol 315 (5) ◽  
pp. E912-E923 ◽  
Author(s):  
Marina Sokolova ◽  
Afaf Sahraoui ◽  
Merete Høyem ◽  
Jonas Øgaard ◽  
Egil Lien ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Ex Vivo ◽  
Cell Damage ◽  
Macrophage Infiltration ◽  
Β Cell ◽  
Beneficial Effects ◽  
Islet Dysfunction

Inflammasomes are multiprotein inflammatory platforms that induce caspase-1 activation and subsequently interleukin (IL)-1β and IL-18 processing. The NLRP3 inflammasome is activated by different forms of oxidative stress, and, based on the central role of IL-1β in the destruction of pancreatic islets, it could be related to the development of diabetes. We therefore investigated responses in wild-type C57Bl/6 (WT) mice, NLRP3−/− mice, and mice deficient in apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) after exposing islets to short-term hypoxia or alloxan-induced islet damage. NLRP3-deficient islets compared with WT islets had preserved function ex vivo and were protected against hypoxia-induced cell death. Furthermore, NLRP3 and ASC-deficient mice were protected against oxidative stress-induced diabetes caused by repetitive low-dose alloxan administration, and this was associated with reduced β-cell death and reduced macrophage infiltration. This suggests that the beneficial effect of NLRP3 inflammasome deficiency on oxidative stress-mediated β-cell damage could involve reduced macrophage infiltration and activation. To support the role of macrophage activation in alloxan-induced diabetes, we injected WT mice with liposomal clodronate, which causes macrophage depletion before induction of a diabetic phenotype by alloxan treatment, resulting in improved glucose homeostasis in WT mice. We show here that the NLRP3 inflammasome acts as a mediator of hypoxia and oxidative stress in insulin-producing cells, suggesting that inhibition of the NLRP3 inflammasome could have beneficial effects on β-cell preservation.

scholarly journals Momordica charantia L. Fruit Fractions inhibit Malondialdehyde Level and Regenerate Hepatic Damage of Hyperglycemic Rats

2020 ◽  
Vol 12 (1) ◽  
pp. 57-61
Author(s):  
Parawansah Parawansah ◽  
I Putu Sudayasa ◽  
Andi Noor Kholidha Syarifin ◽  
Amirudin Eso ◽  
Nuralifah Nuralifah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ethyl Acetate ◽  
Histopathological Examination ◽  
Momordica Charantia ◽  
Hepatic Damage ◽  
Hexane Fraction ◽  
Central Vein ◽  
White Rats ◽  
Chronic Hyperglycemia

BACKGROUND: Chronic hyperglycemia causes an increase of free radical production and in longterm, the hyperglycemia increases oxidative stress. Among medicinal plants, Momordica charantia L. fruit has been known to overcome hyperglycemia. However, role of M. charantia L. fruit on oxidative stress is not well understood. Therefore, current study was conducted to investigate the effect of M. charantia L. fruit extract on malondialdehyde (MDA) level and hepatic damage in hyperglicemic rat model.METHODS: Twenty five white rats (Rattus novergicus) were induced with Streptozotocin (STZ) and treated with/without glibenclamide, sodium carboxymethyl cellulose (Na-CMC), or M. charantia L. fruit ethanol/ethyl acetate/ n-hexane fraction. After the treatment, rat’s livers were collected and separated for histopathological examination and MDA analysis.RESULTS: The MDA level average of rats before the STZ induction was 1.37 μg/mL. MDA level average was markedly increased (23.85 μg/mL) in rats induced with STZ and treated with Na-CMC merely. The MDA level average of STZ-induced glibenclamide-treated rats was 3.12 μg/mL. Meanwhile, the MDA level averages of STZ-induced M. charantia L. fruit ethanol, ethyl acetate and n-hexane fractions-treated rats were 14.95, 8.98 and 5.37 μg/mL, respectively. The histopathology results of this study showed that adipocytes, dilated sinusoids and central vein thickening were mostly observed in STZ-induced Na-CMC-treated rats. Meanwhile, the STZ-induced ethanol/ethyl acetate/n-hexane fraction-treated rats did not exhibitthose expressions.CONCLUSION: M. charantia L. fruit fractions inhibit the MDA level average in liver tissue and regenerate hepatic damage of STZ-induced rats, especially the n-hexane fraction which could be a potential hepatic antioxidant and regenerative agent.KEYWORDS: Momordica charantia L., malondialdehyde, oxidative stress, hyperglycemia, diabetes mellitus

792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Tumorigenic Potential ◽  
Bladder Cancer Cells
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