scholarly journals N-acetylcysteine alleviates PCB52-induced hepatotoxicity by repressing oxidative stress and inflammatory responses

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9720
Author(s):  
Wen-Tao Zhou ◽  
Li-Bin Wang ◽  
Hao Yu ◽  
Kai-Kai Zhang ◽  
Li-Jian Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Inflammatory Responses ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Nrf2 Pathway ◽  
Protein Levels ◽  
Saline Pretreatment

Polychlorinated biphenyls (PCBs), particularly low chlorinated congeners in our environment, can induce human hepatotoxicity. However, the mechanisms by which PCBs cause hepatotoxicity remain elusive. Moreover, there are no effective treatments for this condition. In this study, 40 μM PCB52 was administered to rat (Brl-3A) and human hepatocytes (L-02) for 48 h following the N-acetylcysteine (NAC)/saline pretreatment. A significant decrease in cell viability was observed in PCB52-treated cells relative to the control. Besides, PCB52 significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents, suggesting induction of oxidative stress. The expression of Traf6, MyD88, and Tnf in Brl-3A cells and that of MYD88, TNF, and IL1B in L-02 cells were significantly upregulated by PCB52. Consistently, overexpression of TLR4, MyD88, Traf6, and NF-κB p65 proteins was observed in PCB52-treated cells, indicating activation of inflammatory responses. Nevertheless, no changes in kelch-like ECH-associated protein 1 (keap1), nuclear factor-erythroid 2-related factor (nrf2), and heme oxygenase-1 proteins were observed in PCB52-treated cells, indicating non-activation of the keap1/nrf2 pathway. Pretreatment with NAC significantly ameliorated PCB52 effects on cell viability, ROS levels, MDA contents and expression of inflammatory elements at both RNA and protein levels. However, no changes in keap1, nrf2 and HO-1 protein levels were detected following NAC pretreatment. Taken together, with non-activated keap1/nrf2 pathway, PCB52-induced oxidative stress and inflammatory responses could be responsible for its hepatotoxicity. These effects were effectively attenuated by NAC pretreatment, which scavenges ROS and dampens inflammatory responses. This study might provide novel strategies for the treatment of the PCBs-associated hepatotoxic effects.

Nuclear factor erythroid 2-related factor 2 rescues the oxidative stress induced by di-N-butylphthalate in testicular Leydig cells

2014 ◽  
Vol 34 (2) ◽  
pp. 145-152 ◽  
Author(s):  
B Shen ◽  
W Wang ◽  
L Ding ◽  
Y Sao ◽  
Y Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cells ◽  
Target Genes ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes ◽  
Protein Levels

Aim: This study aimed to determine whether nuclear factor erythroid 2-related factor 2 antagonized the oxidative stress induced by di- N-butylphthalate (DBP) in testicular Leydig cells. Methods: Mouse TM3 testicular Leydig cells were treated with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP. Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and the effects of Nrf2 inducer sulphoraphane (SFN) were tested. Results: DBP induced intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and protein levels of Nrf2 were increased together with its target genes, namely heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP. Conclusion: Increased Nrf2 activity, for example, by SFN can effectively antagonize the oxidative stress in testicular Leydig cells caused by DBP.

scholarly journals Prodigiosin Promotes Nrf2 Activation to Inhibit Oxidative Stress Induced by Microcystin-LR in HepG2 Cells

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 403 ◽  
Author(s):  
Jihua Chen ◽  
Yuji Li ◽  
Fuqiang Liu ◽  
De-Xing Hou ◽  
Jingjing Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Anticancer Properties ◽  
Nrf2 Activation ◽  
Nrf2 Protein ◽  
Related Phase

Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future.

scholarly journals Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

2020 ◽  
Vol 19 (7) ◽  
pp. 1359-1364
Author(s):  
Xu Chen ◽  
Yingjie Cao ◽  
Naifeng Guo ◽  
Guoyuan Lu
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Underlying Mechanism ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Protein Levels ◽  
Proximal Tubular Epithelial Cells ◽  
Ldh Release ◽  
Induced Apoptosis

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 μM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used todetermine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzymelinked immunosorbent assay (ELISA).Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin. Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1

scholarly journals Clusterin Protects Against Cr(VI)-Induced Oxidative Stress-Associated Hepatotoxicity By Mediating The Akt-Keap1-Nrf2 Signaling Pathway

2021 ◽  
Author(s):  
Yu Ma ◽  
Siwen Li ◽  
Sixuan Tang ◽  
Shuzi Ye ◽  
Ningjuan Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Environmental Pollutant ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Intervention Measures ◽  
Exposed Population ◽  
Nrf2 Signaling Pathway

Abstract Hexavalent chromium [Cr(VI)] is a serious environmental pollutant and threatens human health. Although it has been confirmed that oxidative stress is the main mechanism of liver injury caused by Cr(VI) exposure, the related toxic target and effective intervention measures have not been found. Clusterin (CLU) is an acute phase response protein with cytoprotective and apoptosis delaying effects, and its expression has been confirmed to increase significantly after exposure to Cr(VI). In this study, we demonstrate that CLU acts on the Protein Kinase B (PKB/Akt)-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway to release Nrf2 into the nucleus. This to initiates the expression of a downstream protein, heme oxygenase 1 (HO-1), thereby attenuating the ubiquitination ability of Keap1 with Nrf2. We also demonstrated that CLU can affect oxidative stress through the Akt/Nrf2 pathway, which reduces the production of reactive oxygen species (ROS) induced by Cr(VI) and protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity. This study demonstrates a the mechanism of Cr(VI)-induced hepatotoxicity, and indicates that CLU as an intervention target of oxidative stress can provide valuable experimental basis for the prevention and treatment of occupational diseases in Cr(VI)-exposed population.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

scholarly journals Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3174
Author(s):  
Nhung Quynh Do ◽  
Shengdao Zheng ◽  
Bom Park ◽  
Quynh T. N. Nguyen ◽  
Bo-Ram Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
High Glucose ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Related Factor ◽  
Nuclear Factor ◽  
Fruit Extract ◽  
Activated T Cells

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

scholarly journals (–)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 856
Author(s):  
Eui-Jeong Han ◽  
Ilekuttige Priyan Shanura Fernando ◽  
Hyun-Soo Kim ◽  
Dae-Sung Lee ◽  
Areum Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Κb ◽  
Sargassum Horneri ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Hacat Keratinocytes ◽  
Tnf Α ◽  
Ifn Γ

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

scholarly journals The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 610 ◽  
Author(s):  
Yanzhuo Kong ◽  
Kenneth J. Olejar ◽  
Stephen L. W. On ◽  
Venkata Chelikani
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Pathogenic Microorganisms ◽  
Gi Tract ◽  
Lactobacillus Spp

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI tract is usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms and dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role in modulating oxidative stress in cells and tissues, especially in the GI tract. Oxidative stress is linked with excessive reactive oxygen species (ROS) that can be formed by a few enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). The redox mechanisms of Lactobacillus spp. may contribute to the downregulation of these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf-2) and nuclear factor kappa B (NF-κB) are two common transcription factors, through which Lactobacillus spp. modulate oxidative stress as well. As oxidative stress is closely associated with inflammation and certain diseases, Lactobacillus spp. could potentially be applied for early treatment and amelioration of these diseases, either individually or together with prebiotics. However, further research is required for revealing their mechanisms of action as well as their extensive application in the future.

scholarly journals (10Z)-Debromohymenialdisine from Marine Sponge Stylissa sp. Regulates Intestinal Inflammatory Responses in Co-Culture Model of Epithelial Caco-2 Cells and THP-1 Macrophage Cells

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3394 ◽  
Author(s):  
Seon Min Lee ◽  
Na-Hyun Kim ◽  
Sangbum Lee ◽  
Yun Na Kim ◽  
Jeong-Doo Heo ◽  
...  
Keyword(s):  
Marine Sponge ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Subsequent Increase ◽  
Vitro Model ◽  
Factor Α

Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1β, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1–5 μM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.

scholarly journals Activation of the Nrf2/HO-1 Pathway by Amomum villosum Extract Suppresses LPS-Induced Oxidative Stress In Vitro and Ex Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Dong-Woo Lim ◽  
Hee-Jin Choi ◽  
Sun-Dong Park ◽  
Hyuck Kim ◽  
Ga-Ram Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Ethanol Extract ◽  
Peritoneal Macrophages ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Anti Inflammatory

Despite its deleterious effects on living cells, oxidative stress plays essential roles in normal physiological processes and provides signaling molecules for cell growth, differentiation, and inflammation. Macrophages are equipped with antioxidant mechanisms to cope with intracellular ROS produced during immune response, and Nrf2 (NF-E2-related factor 2)/HO-1 (heme oxygenase-1) pathway is an attractive target due to its protective effect against ROS-induced cell damage in inflamed macrophages. We investigated the effects of ethanol extract of A. villosum (AVEE) on lipopolysaccharide- (LPS-) stimulated inflammatory responses generated via the Nrf2/HO-1 signaling pathway in murine peritoneal macrophages and RAW 264.7 cells. AVEE was found to suppress the NF-κB signaling pathway, thus, to reduce proinflammatory cytokine, nitric oxide, and prostaglandin levels in peritoneal macrophages and Raw 264.7 cells treated with LPS, and to enhance HO-1 expression by activating Nrf2 signaling. Furthermore, these anti-inflammatory effects of AVEE were diminished when cells were pretreated with SnPP (a HO-1 inhibitor). HPLC analysis revealed AVEE contained quercetin, a possible activator of the Nrf2/HO-1 pathway. These results show A. villosum ethanol extract exerts anti-inflammatory effects by activating the Nrf2/HO-1 pathway in LPS-stimulated macrophages.

Sign in / Sign up

Export Citation Format

Share Document