scholarly journals Proanthocyanidins Protect against β-Hydroxybutyrate-Induced Oxidative Damage in Bovine Endometrial Cells

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 400 ◽  
Author(s):  
Xi Cheng ◽  
Shuhua Yang ◽  
Chuang Xu ◽  
Lanzhi Li ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Signaling Pathway ◽  
Manganese Superoxide Dismutase ◽  
Metabolic Diseases ◽  
Heme Oxygenase 1 ◽  
Endometrial Cells ◽  
Manganese Superoxide ◽  
Nrf2 Signaling Pathway ◽  
Mrna And Protein Expression ◽  
Stress Damage

Metabolic diseases, such as ketosis, are closely associated with decreased reproductive performance (such as delayed estrus and decreased pregnancy rate) in dairy cows. The change of β-hydroxybutyrate (BHBA) concentration in dairy cattle is an important mechanism leading to ketosis, and its blood concentration in ketotic cows is always significantly higher than in nonketotic cows. Many studies indicated that BHBA can induce oxidative damage in liver and other organs. Proanthocyanidins (PCs) have gained substantial attention in the last decade as strong antioxidative substances. This study aimed to demonstrate a protective effect of PCs against BHBA-induced oxidative stress damage in bovine endometrial (BEND) cells by activating the nuclear erythroid2-related factor2 (Nrf2) signaling pathway. Our research show that PCs could significantly increase activities of catalase (CAT) and glutathione peroxidase (GSH-PX), glutathione (GSH) content, and antioxidant capacity (T-AOC), while significantly decreasing malondialdehyde (MDA) content in BEND cells. Both mRNA and protein expression levels of Nrf2 were significantly increased in BEND cells, and glutamate–cysteine ligase catalytic subunit (GCLC), heme oxygenase 1 (HO-1), manganese superoxide dismutase (Mn-SOD), and NAD(P)H quinone dehydrogenase 1 (NQO-1) were also significantly increased. These results indicate that PCs can antagonize BHBA-induced oxidative damage by activating the Nrf2 signaling pathway to exert an antioxidant effect.

scholarly journals Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Mengchuan Xu ◽  
Qiang Niu ◽  
Yunhua Hu ◽  
Gangling Feng ◽  
Haixia Wang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Oxidative Stress Marker ◽  
Average Growth ◽  
Methylation Index ◽  
Arsenic Methylation ◽  
Nrf2 Signaling Pathway ◽  
Mrna And Protein Expression

Purpose. To investigate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative damage and arsenic (As) methylation and to clarify the role of Nrf2 in the process. Methods. L-02 cells were treated with arsenic (25 μM) and GSPE (10, 25, and 50 mg/L) for 24 h. Cell viability was analyzed by MTT assay. Cell apoptosis and ROS fluorescence were detected by flow cytometry. Oxidative stress marker levels were measured using commercial kits. mRNA and protein expression were detected by qRT-PCR and western blotting. The cellular concentrations of methylation products were measured by HPLC-HGAFS. Arsenic methylation ability of cells was determined. Results. Cell survival rate was significantly lower in the As group than in the control group (P<0.05), while cell apoptosis increased and the number of apoptotic cells decreased gradually after GSPE intervention. Superoxide dismutase, glutathione, and sulfhydryl levels in the intervention group were significantly higher (P<0.05), while MDA and ROS levels were significantly lower (P<0.05) than those in the As group. The mRNA and protein expression of Nrf2, HO-1, NQO1, and glutathione-S-transferase increased in the As + GSPE group compared with that in the As group (P<0.05). GSPE significantly increased methylated As level, primary methylation index, secondary methylation index, average growth rate of methylation, and average methylation speed compared with the GSPE untreated group (P<0.05). After Nrf2 inhibition, the effect of GSPE decreased significantly. Conclusion. GSPE activates the Nrf2 signaling pathway to antagonize As-induced oxidative damage and to promote As methylation metabolism. Therefore, GSPE may be a potential agent for relieving As-induced hepatotoxicity.

scholarly journals Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 158
Author(s):  
Li Kong ◽  
Lijuan Zhu ◽  
Xianglian Yi ◽  
You Huang ◽  
Haoqiang Zhao ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Erythroid Cell ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

T-2 toxin, which is mainly produced by specific strains of Fusarium in nature, can induce immunotoxicity and oxidative stress, resulting in immune organ dysfunction and apoptosis. Betulinic acid (BA), a pentacyclic triterpenoids from nature plants, has been demonstrated to possess immunomodulating and antioxidative bioactivities. The purpose of the study was to explore the effect of BA on T-2 toxin-challenged spleen oxidative damage and further elucidate the underlying mechanism. We found that BA not only ameliorated the contents of serum total cholesterol (TC) and triglyceride (TG) but also restored the number of lymphocytes in T-2 toxin-induced mice. BA dose-dependently reduced the accumulation of reactive oxygen species (ROS), enhanced superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content, as well as increased the total antioxidant capacity (T-AOC) in the spleen of T-2-toxin-exposed mice. Moreover, BA reduced inflammatory cell infiltration in the spleen, improved the morphology of mitochondria and enriched the number of organelles in splenocytes, and dramatically attenuated T-2 toxin-triggered splenocyte apoptosis. Furthermore, administration of BA alleviated the protein phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERK); decreased the protein expression of kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein1 (Keap1); and increased the protein expression of nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the spleen. These findings demonstrate that BA defends against spleen oxidative damage associated with T-2 toxin injection by decreasing ROS accumulation and activating the Nrf2 signaling pathway, as well as inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.

scholarly journals Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Guosheng Lin ◽  
Dandan Luo ◽  
Jingjing Liu ◽  
Xiaoli Wu ◽  
Jinfen Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Hepatoprotective Effect ◽  
Dendrobium Officinale ◽  
Regulatory Subunit ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

scholarly journals Bovine Herpesvirus 1 Productive Infection Led to Inactivation of Nrf2 Signaling through Diverse Approaches

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Xiaotian Fu ◽  
Dongmei Chen ◽  
Yan Ma ◽  
Weifeng Yuan ◽  
Liqian Zhu
Keyword(s):  
Signaling Pathway ◽  
Bovine Herpesvirus ◽  
Productive Infection ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Herpesvirus Type ◽  
Nrf2 Signaling Pathway ◽  
Mdbk Cells ◽  
Bovine Herpesvirus Type 1

Bovine herpesvirus type 1 (BoHV-1) is a significant cofactor for bovine respiratory disease complex (BRDC), the most important inflammatory disease in cattle. BoHV-1 infection in cell cultures induces overproduction of pathogenic reactive oxygen species (ROS) and the depletion of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a master transcriptional factor regulating a panel of antioxidant and cellular defense genes in response to oxidative stress. In this study, we reported that the virus productive infection in MDBK cells at the later stage significantly decreased the expression levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) proteins, the canonical downstream targets regulated by Nrf2, inhibited Nrf2 acetylation, reduced the accumulation of Nrf2 proteins in the nucleus, and relocalized nuclear Nrf2 proteins to form dot-like staining patterns in confocal microscope assay. The differential expression of Kelch-like ECH associated protein 1 (KEAP1) and DJ-1 proteins as well as the decreased association between KEAP1 and DJ-1 promoted Nrf2 degradation through the ubiquitin proteasome pathway. These data indicated that the BoHV-1 infection may significantly suppress the Nrf2 signaling pathway. Moreover, we found that there was an association between Nrf2 and LaminA/C, H3K9ac, and H3K18ac, and the binding ratios were altered following the virus infection. Taken together, for the first time, we provided evidence showing that BoHV-1 infection inhibited the Nrf2 signaling pathway by complicated mechanisms including promoting Nrf2 degradation, relocalization of nuclear Nrf2, and inhibition of Nrf2 acetylation.

scholarly journals Brain Vessels Normally Undergo Cyclic Activation and Inactivation: Evidence from Tumor Necrosis Factor-α, Heme Oxygenase-1, and Manganese Superoxide Dismutase Immunostaining of Vessels and Perivascular Brain Cells

2001 ◽  
Vol 21 (3) ◽  
pp. 244-252 ◽  
Author(s):  
Christl A. Ruetzler ◽  
Kazuhide Furuya ◽  
Hidetaka Takeda ◽  
John M. Hallenbeck
Keyword(s):  
Superoxide Dismutase ◽  
Tumor Necrosis ◽  
Manganese Superoxide Dismutase ◽  
Heme Oxygenase 1 ◽  
Cyclic Activation ◽  
Brain Vessels ◽  
Spontaneously Hypertensive ◽  
Manganese Superoxide ◽  
Tnf Α ◽  
Necrosis Factor

Studies of vascular biology during the past decade have identified an expanding list of agonists and antagonists that regulate local hemostasis, inflammation, and reactivity in blood vessels. Interactions at the blood-endothelial interface are intricate and complex and have been postulated to play a role in the initiation of stroke and the progression of brain injury during early hours of ischemia, particularly in conjunction with reperfusion injury ( Hallenbeck, 1996 ). In the current study of normal and activated vessels in rat brain, immunoreactive tumor necrosis factor-alpha (TNF-α), heme oxygenase-1 (HO-1), and manganese superoxide dismutase (MnSOD) exhibit concentric perivascular rings involving vessel wall and surrounding parenchyma that appear to coincide with one another in serial sections. The ring patterns suggest periodic radial expansion of these molecules released through a process of cyclic activation and inactivation of brain vessel segments. In this process, the rings appear randomly scattered instead of affecting all vessels within a high power field (HPF) synchronously. The average number of vessels per HPF (mean ± SD) with perivascular cuffs of immunoreactive MnSOD increased from 51 ± 28 in Wistar, 72 ± 46 in Wistar-Kyoto, and 84 ± 30 in Sprague Dawley rats (no spontaneous strokes) to 184 ± 72 in spontaneously hypertensive stroke-prone rats (spontaneous strokes). Perivascular immunoreactive cuffs are also increased in spontaneously hypertensive rats by induction of cytokine expression by lipopolysaccharide (64 ± 15 vs. 131 ± 32 /HPF). The patterns of TNF-α, HO-1, and MnSOD in naïve animals are interpreted to indicate that focal hemostatic balance normally fluctuates in brain vessels and influences surrounding parenchymal cells. Perivascular immunoreactive cuffs representing this process are more frequent in animals with lipopolysaccharide-induced endothelial activation or genetic stroke proneness.

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway

2016 ◽  
Vol 94 (5) ◽  
pp. 517-525 ◽  
Author(s):  
Jinlian Li ◽  
Yanli Zhang ◽  
Haiyun Luan ◽  
Xuehong Chen ◽  
Yantao Han ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Damage ◽  
Binding Activity ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Akt Inhibitor ◽  
Nrf2 Signaling Pathway

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.

Effect of melatonin on attenuating the isoflurane-induced oxidative damage is related to PKCα/Nrf2 signaling pathway in developing rats

2018 ◽  
Vol 143 ◽  
pp. 9-18 ◽  
Author(s):  
Bei Li ◽  
Xiu Jing Feng ◽  
Xue Yuan Hu ◽  
Yong Ping Chen ◽  
Ji Chen Sha ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Signaling Pathway ◽  
Nrf2 Signaling Pathway
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