scholarly journals K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques

2021 ◽  
Author(s):  
Xiaolei Wang ◽  
Zhe Sun ◽  
Ruosen Yuan ◽  
Weifeng Zhang ◽  
Yejiao Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Necrotic Core ◽  
Control Group ◽  
Autophagic Flux ◽  
Plaque Progression ◽  
Core Formation ◽  
Vulnerable Plaques ◽  
Macrophage Apoptosis ◽  
Cellular Apoptosis

Abstract Purpose Macrophage apoptosis coupled with a defective phagocytic clearance of the apoptotic cells promotes plaque necrosis in advanced atherosclerosis, which causes acute atherothrombotic vascular disease. Nonsteroidal anti-inflammatory drug sulindac derivative K-80003 treatment was previously reported to dramatically attenuate atherosclerotic plaque progression and destabilization. However, the underlying mechanisms are not fully understood. This study aimed to determine the role of K-80003 on macrophage apoptosis and elucidate the underlying mechanism. Methods The mouse model of vulnerable carotid plaque in ApoE−/− mice was developed in vivo. Consequently, mice were randomly grouped into two study groups: the control group and the K-80003 group (30 mg/kg/day). Samples of carotid arteries were collected to determine atherosclerotic necrotic core area, cellular apoptosis, and oxidative stress. The effects of K-80003 on RAW264.7 macrophage apoptosis, oxidative stress, and autophagic flux were also examined in vitro. Results K-80003 significantly suppressed necrotic core formation and inhibited cellular apoptosis of vulnerable plaques. K-80003 can also inhibit 7-ketocholesterol-induced macrophage apoptosis in vitro. Furthermore, K-80003 inhibited intraplaque cellular apoptosis mainly through the suppression of oxidative stress, which is a key cause of advanced lesional macrophage apoptosis. Mechanistically, K-80003 prevented 7-ketocholesterol-induced impairment of autophagic flux in macrophages, evidenced by the decreased LC3II and SQSTM1/p62 expression, GFP-RFP-LC3 cancellation upon K-80003 treatment. Conclusion Inhibition of macrophage apoptosis and necrotic core formation by autophagy-mediated reduction of oxidative stress is one mechanism of the suppression of plaque progression and destabilization by K-80003.

scholarly journals proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bangkun Yang ◽  
Lesheng Wang ◽  
Ying Nie ◽  
Wei Wei ◽  
Wenping Xiong
Keyword(s):  
Neural Plasticity ◽  
Cell Model ◽  
Neurotrophin Receptor ◽  
Control Group ◽  
P75 Neurotrophin Receptor ◽  
Post Stroke ◽  
Post Stroke Depression ◽  
Cellular Apoptosis ◽  
Related Proteins

AbstractBrain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.

scholarly journals Macrophage autophagy regulates mitochondria‐mediated apoptosis and inhibits necrotic core formation in vulnerable plaques

2020 ◽  
Vol 24 (1) ◽  
pp. 260-275 ◽  
Author(s):  
Qingqing Xiao ◽  
Xinyu Che ◽  
Bin Cai ◽  
Zhenyu Tao ◽  
Hengyuan Zhang ◽  
...  
Keyword(s):  
Necrotic Core ◽  
Core Formation ◽  
Vulnerable Plaques

scholarly journals mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yiru Xia ◽  
Mengjun Sun ◽  
Yufeng Xie ◽  
Rong Shu
Keyword(s):  
Oxidative Stress ◽  
Poor Response ◽  
Control Group ◽  
Oxygen Species ◽  
Gingival Fibroblasts ◽  
Periodontal Pathogens ◽  
Mtor Inhibition ◽  
Mechanistic Target Of Rapamycin ◽  
Beta Galactosidase

The aging periodontium may be vulnerable to periodontal pathogens and poor response to inflammation and susceptible to tumorigenesis. Human gingival fibroblasts (hGFs) through continuously replicative culture served as an in vitro surrogate for aging. To investigate the effects of the mechanistic target of rapamycin (mTOR) inhibition on the aging gingiva, we stimulated the high-passage hGFs with rapamycin (20 nmol/L) for 3 days and 30 days. The cellular and biological changes were examined by immunofluorescence, real-time PCR, ELISA, Western blotting, and flow cytometry. The data demonstrated that the inhibition of mTOR signaling led to fewer senescence-associated beta-galactosidase- (SA-β-Gal-) positive cells, delayed the onset of senescence, preserved the capability of proliferation, and lowered the expression levels of relevant senescence-associated markers, such as p16INK4a, p21CIP1a, interleukin-6 (IL-6), and IL-8. In addition, when infected by prominent periodontal pathogens, Porphyromonas gingivalis (ATCC 33277), rapamycin-pretreated groups decreased the expression of inflammatory cytokines (IL-6 and IL-8) compared with the control group. mTOR inhibition upregulated the gene expression of antioxidant components (Cat, Sod2, and Prdx3; P<0.05) and consequently neutralized the excessive reactive oxygen species (ROS). In conclusion, our results indicated that mTOR inhibition might rejuvenate the aging gingiva to some extent and relieve inflammation through eliminating oxidative stress.

scholarly journals Protective Effect of Decursin Extracted fromAngelica gigasin Male Infertility via Nrf2/HO-1 Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Woong Jin Bae ◽  
U. Syn Ha ◽  
Jin Bong Choi ◽  
Kang Sup Kim ◽  
Su Jin Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Semen Quality ◽  
Antioxidant Activities ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Testicular Weight ◽  
Unilateral Cryptorchidism

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted fromAngelica gigasNakai on antioxidant activityin vitroand in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg ofA. gigasextract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment withA. gigasextract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted fromA. gigasis a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

Supplementation of kaempferol to in vitro maturation medium regulates oxidative stress and enhances subsequent embryonic development in vitro

Zygote ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 59-64
Author(s):  
Yuhan Zhao ◽  
Yongnan Xu ◽  
Yinghua Li ◽  
Qingguo Jin ◽  
Jingyu Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Treated Group ◽  
Control Group ◽  
Oxygen Species

SummaryKaempferol (KAE) is one of the most common dietary flavonols possessing biological activities such as anticancer, anti-inflammatory and antioxidant effects. Although previous studies have reported the biological activity of KAE on a variety of cells, it is not clear whether KAE plays a similar role in oocyte and embryo in vitro culture systems. This study investigated the effect of KAE addition to in vitro maturation on the antioxidant capacity of embryos in porcine oocytes after parthenogenetic activation. The effects of kaempferol on oocyte quality in porcine oocytes were studied based on the expression of related genes, reactive oxygen species, glutathione and mitochondrial membrane potential as criteria. The rate of blastocyst formation was significantly higher in oocytes treated with 0.1 µm KAE than in control oocytes. The mRNA level of the apoptosis-related gene Caspase-3 was significantly lower in the blastocysts derived from KAE-treated oocytes than in the control group and the mRNA expression of the embryo development-related genes COX2 and SOX2 was significantly increased in the KAE-treated group compared with that in the control group. Furthermore, the level of intracellular reactive oxygen species was significantly decreased and that of glutathione was significantly increased after KAE treatment. Mitochondrial membrane potential (ΔΨm) was increased and the activity of Caspase-3 was significantly decreased in the KAE-treated group compared with that in the control group. Taken together, these results suggested that KAE is beneficial for the improvement of embryo development by inhibiting oxidative stress in porcine oocytes.

scholarly journals Solid Lipid Nanoparticles of Myricitrin Have Antioxidant and Antidiabetic Effects on Streptozotocin-Nicotinamide-Induced Diabetic Model and Myotube Cell of Male Mouse

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Akram Ahangarpour ◽  
Ali Akbar Oroojan ◽  
Layasadat Khorsandi ◽  
Maryam Kouchak ◽  
Mohammad Badavi
Keyword(s):  
Oxidative Stress ◽  
C2c12 Cell ◽  
In Vitro Study ◽  
Homogenization Method ◽  
Solid Lipid ◽  
Muscle Tissues ◽  
Diabetic Model ◽  
Cellular Apoptosis

Type 2 diabetes mellitus (T2DM) may occur via oxidative stress. Myricitrin is a plant-derived antioxidant, and its solid lipid nanoparticle (SLN) may be more potent. Hence, the present study was conducted to evaluate the effects of myricitrin SLN on streptozotocin-nicotinamide- (STZ-NA-) induced T2DM of the mouse and hyperglycemic myotube. In this experimental study, cold homogenization method was used to prepare SLN. Then, 120 adult male NMRI mice were divided into 7 groups: control, vehicle, diabetes (received STZ 65 mg/kg 15 min after injected NA 120 mg/kg), diabetes + SLN containing myricitrin 1, 3, and 10 mg/kg, and diabetes + metformin. For in vitro study, myoblast (C2C12) cell line was cultured and divided into 6 groups (n=3): control, hyperglycemia, hyperglycemia + SLN containing myricitrin 1, 3, and, 10 μM, and hyperglycemia + metformin. After the last nanoparticle treatment, plasma samples, pancreas and muscle tissues, and myotubes were taken for experimental assessments. Diabetes increased lipid peroxidation and reduced antioxidant defense along with the hyperglycemia, insulin resistance, and pancreas apoptosis. Hyperglycemia induced oxidative stress, antioxidant impairment, and cellular apoptosis. Myricitrin SLN improved diabetes and hyperglycemia complications in the in vivo and in vitro studies. Therefore, SLN of myricitrin showed antioxidant, antidiabetic, and antiapoptotic effects in the mouse and myotube cells.

Antioxidant potential of thyme extract: alleviation of N-nitrosodiethylamine-induced oxidative stress

2008 ◽  
Vol 27 (3) ◽  
pp. 215-221 ◽  
Author(s):  
P Rana ◽  
G Soni
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Test Group ◽  
Normal Diet ◽  
Lower Degree ◽  
Control Group ◽  
Albino Rats ◽  
Stress Induction ◽  
And Control

Protective role of thyme extract against N-nitrosodiethylamine (NDEA)-induced oxidative stress has been evaluated in albino rats. For this, one group of rats were fed diet supplemented with thyme extract (0.5%) and served as the test group, whereas animals of the other group fed on normal diet served as the control group. The rats were fed on respective diets for a period of 2 weeks after which stress was induced to half the animals of each group by i.p. administration of NDEA at 200 mg/kg body weight. Animals were killed 48 h post stress-induction period. Feed intake and body weight decreased significantly in both test and control groups, the effect being less in test group. Increase in osmotic fragility and in-vitro lipid peroxidation (LPO) on stress induction was of lower degree in the test group. NDEA toxicity was mainly reflected in liver as evidenced by increased activities of plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. The effect was of lower degree in test group as compared with that in the control group. Increase in urea levels observed following NDEA administration was also of lower degree in test groups. Blood glutathione (GSH) levels increased more so in test group compared with control group on stress induction. The activities of superoxide dismutase (SOD), peroxidase (Px), and catalase (CAT) activities decreased significantly on stress induction in erythrocytes. LPO increased in all the tissues through varying degree, and the increase was appreciably of lower degree in test group. The activity of SOD increased significantly in both test and control group on stress induction, whereas activities of Px and CAT decreased following NDEA treatment, and the effects were of lower degree in test group. Thus, supplementation of diet with thyme extract can improve antioxygenic potential and hence help to prevent oxidative stress.

scholarly journals Octreotide ameliorates hypoxia/reoxygenation-induced cerebral infarction by inhibiting oxidative stress, inflammation and apoptosis, and via inhibition of TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
Vol 20 (11) ◽  
pp. 2261-2266
Author(s):  
Yanbin Hou ◽  
Zhongze Lou ◽  
Yunxin Ji ◽  
Liemin Ruan ◽  
He Gao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Control Group ◽  
N2a Cells ◽  
Tnf Α ◽  
Octreotide Treatment ◽  
Vitro Model ◽  
Hypoxia Reoxygenation

Purpose: To explore the effects of octreotide (OCT) on oxidative stress, inflammation and apoptosis in hypoxia/reoxygenation (H/R)-induced cerebral infarction.Methods: The in vitro model of cerebral infarction was established by treating N2A cells with hypoxia for 4 h and reoxygenation for 24 h. The viability of N2A cells was determined by CCK-8 assay. The cells were divided into 3 groups: control group, H/R group, and H/R+OCT group. The cells in H/R+OCT group were pretreated with OCT (60 ng/mL) before H/R treatment. The oxidative stress of N2A cells were assessed by determining the levels of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), reactive oxygen species (ROS) and malondialdehyde (MDA). Inflammation of N2A cells was evaluated by evaluating the levels of TNF-α, IL-1β, IL-6, and IL-8, while the apoptosis of N2A cells was assessed by flow cytometry. Western blot analysis was used to determine the expression of Bcl-2, Bax, TLR4, MyD88, and NF-κB.Results: Octreotide treatment significantly reduced the level of oxidative stress. The inflammation of N2A cells caused by hypoxia/reoxygenation was inhibited by treatment with octreotide. Apoptosis of N2A cells was also inhibited by octreotide treatment. Hypoxia/reoxygenation activated TLR4/MyD88/NF-κB signaling pathway, while octreotide inhibits the activation of this pathway.Conclusion: The results reveal that octreotide inhibits hypoxia/reoxygenation-induced oxidative stress,as well as the inflammation, and apoptosis of N2A cells by inhibiting TLR4/MyD88/NF-κB signaling pathway. Thus, these findings may provide new insights into the treatment of cerebral infarction.

scholarly journals Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Xing Liu ◽  
Zhuoshan Huang ◽  
Yuanyuan Zhang ◽  
Xing Shui ◽  
Fanmao Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Signaling Pathway ◽  
Cell Activity ◽  
Protective Role ◽  
Cell Counting ◽  
Control Group ◽  
Inflammatory Injury ◽  
Beneficial Effects

Background: Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive.Methods: Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial cells (ECs) were pretreated with Lacidipine prior to being stimulated with H2O2, bleomycin, or Lipopolysaccharides (LPS) in vitro. Then, cell activity, migration, and senescence were measured by Cell Counting Kit-8 assay, transwell assay, and β-galactosidase staining, respectively. The fluorescent probe 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) was used to assess the intracellular reactive oxygen species (ROS). Related protein expression was detected by Western blotting and immunofluorescence.Results: Our data showed that Lacidipine treatment lowered the blood pressure of SHRs accompanied by the elevation of CXCR7 expression and suppression of P38 and CCAAT/enhancer-binding protein beta (C/EBP-β) compared with the control group. In vitro experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence, and inflammatory activation via the CXCR7/P38/signaling pathway.Conclusions: Our results suggested that Lacidipine plays a protective role in EC senescence, oxidative stress, and inflammatory injury through the regulation of CXCR7/P38/C/EBP-β signaling pathway.

scholarly journals Resveratrol Hinders Postovulatory Aging by Modulating Oxidative Stress in Porcine Oocytes

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6346
Author(s):  
Benazir Abbasi ◽  
Yan Dong ◽  
Rong Rui
Keyword(s):  
Oxidative Stress ◽  
Polar Body ◽  
Treated Group ◽  
Control Group ◽  
Relative Level ◽  
Antioxidant Genes ◽  
First Polar Body ◽  
Postovulatory Aging ◽  
Relative Mrna Expression

Postovulatory aging of the mammalian oocytes causes deterioration of oocytes through several factors including oxidative stress. Keeping that in mind, we aimed to investigate the potential of a well-known antioxidant, resveratrol (RV), to evaluate the adverse effects of postovulatory aging in porcine oocytes. After in vitro maturation (IVM), a group of (25–30) oocytes (in three replicates) were exposed to 0, 1, 2, and 4 μmol/L of RV, respectively. The results revealed that the first polar body (PB1) extrusion rate of the oocytes significantly increased when the RV concentration reached up to 2 μmol/L (p < 0.05). Considering optimum RV concentration of 2 μmol/L, the potential of RV was evaluated in oocytes aged for 24 and 48 h. We used fluorescence microscopy to detect the relative level of reactive oxygen species (ROS), while GHS contents were measured through the enzymatic method. Our results revealed that aged groups (24 h and 48 h) treated with RV (2 μmol/L) showed higher (p < 0.05) ROS fluorescence intensity than the control group, but lower (p < 0.05) than untreated aged groups. The GSH content in untreated aged groups (24 h and 48 h) was lower (p < 0.05) than RV-treated groups, but both groups showed higher levels than the control. Similarly, the relative expression of the genes involved in antioxidant activity (CAT, GPXGSH-Px, and SOD1) in RV-treated groups was lower (p < 0.05) as compared to the control group but higher than that of untreated aged groups. Moreover, the relative mRNA expression of caspase-3 and Bax in RV-treated groups was higher (p < 0.05) than the control group but lower than untreated groups. Furthermore, the expression of Bcl-2 in the RV-treated group was significantly lower than control but higher than untreated aged groups. Taken together, our findings revealed that the RV can increase the expression of antioxidant genes by decreasing the level of ROS, and its potent antiapoptotic effects resisted against the decline in mitochondrial membrane potential in aged oocytes.

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