scholarly journals Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Liang Zhang ◽  
Liwei Zhou ◽  
Jia Du ◽  
Mengxia Li ◽  
Chengyuan Qian ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Multiple Myeloma ◽  
Cell Lines ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
High Concentration ◽  
Cytochrome C Release ◽  
Apoptotic Pathway

Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

In Vitro Bacterial Cytotoxicity of CNTs: Reactive Oxygen Species Mediate Cell Damage Edges over Direct Physical Puncturing

Langmuir ◽  
2013 ◽  
Vol 30 (2) ◽  
pp. 592-601 ◽  
Author(s):  
Krishnamoorthy Rajavel ◽  
Rajkumar Gomathi ◽  
Sellamuthu Manian ◽  
Ramasamy Thangavelu Rajendra Kumar
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mediate Cell

scholarly journals Reactive Oxygen Species Are Involved in the Development of Gastric Cancer and Gastric Cancer-Related Depression through ABL1-Mediated Inflammation Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Tianhe Huang ◽  
Fuling Zhou ◽  
Xiaohan Yuan ◽  
Tian Yang ◽  
Xuan Liang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
The Cancer Genome Atlas ◽  
Mild Stress ◽  
Oxygen Species ◽  
Mice Model ◽  
Inflammatory Signaling

Background. The mechanisms of crosstalk between depression and gastric cancer (GC) remain ill defined. Given that reactive oxygen species (ROS) is involved in the pathophysiology of both GC and depression, we try to explore the activities of ROS in the development of GC and GC-related depression. Methods. 110 patients with newly diagnosed GC were recruited in our study. The clinical characteristics of these patients were recorded. Inflammation and oxidative stress markers were detected by ELISA. The depression status of patients with GC was assessed during follow-up. The association between ROS, ABL1, and inflammation factors was evaluated in H2O2-treated GC cell lines and The Cancer Genome Atlas (TCGA) database. The effect of ABL1 on inflammation was detected with Imatinib/Nilotinib-treated GC cell lines. A chronic mild stress- (CMS-) induced patient-derived xenograft (PDX) mice model was established to assess the crosstalk between depression and GC. Results. Depression was correlated with poor prognosis of patients with GC. GC patients with depression were under a high level of oxidative status as well as dysregulated inflammation. In the CMS-induced GC PDX mice model, CMS could facilitate the development of GC. Additionally, tumor bearing could induce depressive-like behaviors of mice. With the treatment of ROS, the activities of ABL1 and inflammatory signaling were enhanced both in vitro and in vivo, and blocking the activities of ABL1 inhibited inflammatory signaling. Conclusions. ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression.

scholarly journals Ghrelin Ameliorates Diabetic Retinal Injury: Potential Therapeutic Avenues for Diabetic Retinopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jie Bai ◽  
Fan Yang ◽  
Ruiqi Wang ◽  
Qinghui Yan
Keyword(s):  
Reactive Oxygen Species ◽  
Diabetic Retinopathy ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ros Generation ◽  
Oxygen Species

Ghrelin has anti-inflammatory, antioxidant, and antiapoptotic effects, and it may be beneficial for the treatment of many ophthalmic diseases, such as cataract, uveitis, and glaucoma. Our previous work proved that ghrelin pretreatment reduced the apoptosis of lens epithelial cells induced by hydrogen peroxide, reduced the accumulation of reactive oxygen species (ROS), and effectively maintained the transparency of lens tissue. However, no study has yet investigated the effect of ghrelin on retina. In this study, we conducted in vitro and in vivo experiments to explore the effect of ghrelin on high-glucose- (HG-) induced ARPE-19 cell damage and diabetic retinopathy in streptozotocin-induced diabetic rats. ARPE-19 cells were incubated in a normal or an HG (30 mM glucose) medium with or without ghrelin. Cell viability was measured by 3-(4, 5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide assay, and apoptosis was detected by the Hoechst–PI staining assay. Intracellular reactive oxygen species (ROS) production levels within cells were measured using 2 ′ ,7 ′ -dichlorofluorescein diacetate staining, and the contents of superoxide dismutase and malondialdehyde were measured using relevant detection kits. The expression levels of IL-1β and IL-18 were measured using an enzyme-linked immunosorbent assay, and those of NLRP3, IL-1β, and IL-18 were measured using Western blotting. The rat diabetes models were induced using a single intraperitoneal injection of streptozotocin (80 mg/kg). The morphological and histopathological changes in the retinal tissues were examined. The results indicated that ghrelin reduced ROS generation, inhibited cell apoptosis and the activation of NLRP3 inflammasome, inhibited the apoptosis of retinal cells in diabetic rats, and protected the retina against HG-induced dysfunction. In conclusion, ghrelin may play a role in the treatment of ocular diseases involving diabetic retinopathy.

Effect of melatonin treatment on the developmental potential of parthenogenetic and somatic cell nuclear-transferred porcine oocytes in vitro

Zygote ◽  
2011 ◽  
Vol 20 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Mayu Nakano ◽  
Yoko Kato ◽  
Yukio Tsunoda
Keyword(s):  
Reactive Oxygen Species ◽  
Somatic Cell ◽  
Culture Medium ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Melatonin Treatment ◽  
Developmental Potential

SummaryMelatonin secreted from the mammalian pineal gland is a free-radical scavenger that protects tissues from cell damage. The present study examined the effects of addition of melatonin to the culture medium on the developmental potential of parthenogenetic and somatic cell nuclear-transferred (SCNT) porcine oocytes. Supplementation of the maturation medium with melatonin did not increase the maturation rate, the proportion of oocytes that cleaved and developed into blastocysts after parthenogenetic activation, or the blastocyst cell number compared to controls. When 10−7 M melatonin was added to the culture medium, the proportion of parthenogenetic oocytes that developed to the 2-cell and 4-cell stages was significantly higher than that of controls. The potential of melatonin-treated oocytes to develop into blastocysts was high but not significantly different from that of controls. The addition of 10−7 M melatonin to the culture medium did not increase the preimplantation development of SCNT oocytes. Melatonin treatment significantly reduced the levels of reactive oxygen species in 4-cell parthenogenetic and SCNT embryos, but did not reduce the proportion of apoptotic cells in parthenogenetic and SCNT blastocysts. Although the results indicated that parthenogenetic and SCNT melatonin -treated embryos had significantly lower levels of reactive oxygen species than controls, the potential of melatonin-treated embryos to develop into blastocysts was not significantly higher than that of controls, in contrast to previous reports. The beneficial effects of melatonin on the developmental potential of oocytes might depend on the culture conditions.

scholarly journals Therapeutic Myeloperoxidase Inhibition Attenuates Neutrophil Activation, ANCA-Mediated Endothelial Damage, and Crescentic GN

2019 ◽  
Vol 31 (2) ◽  
pp. 350-364 ◽  
Author(s):  
Marilina Antonelou ◽  
Erik Michaëlsson ◽  
Rhys D.R. Evans ◽  
Chun Jing Wang ◽  
Scott R. Henderson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cell ◽  
T Cell ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Neutrophil Extracellular Trap ◽  
Oxygen Species ◽  
Endothelial Cell Damage ◽  
Anca Associated Vasculitis

BackgroundMyeloperoxidase released after neutrophil and monocyte activation can generate reactive oxygen species, leading to host tissue damage. Extracellular glomerular myeloperoxidase deposition, seen in ANCA-associated vasculitis, may enhance crescentic GN through antigen-specific T and B cell activation. Myeloperoxidase-deficient animals have attenuated GN early on, but augmented T cell responses. We investigated the effect of myeloperoxidase inhibition, using the myeloperoxidase inhibitor AZM198, to understand its potential role in treating crescentic GN.MethodsWe evaluated renal biopsy samples from patients with various forms of crescentic GN for myeloperoxidase and neutrophils, measured serum myeloperoxidase concentration in patients with ANCA-associated vasculitis and controls, and assessed neutrophil extracellular trap formation, reactive oxygen species production, and neutrophil degranulation in ANCA-stimulated neutrophils in the absence and presence of AZM198. We also tested the effect of AZM198 on ANCA-stimulated neutrophil-mediated endothelial cell damage in vitro, as well as on crescentic GN severity and antigen-specific T cell reactivity in the murine model of nephrotoxic nephritis.ResultsAll biopsy specimens with crescentic GN had extracellular glomerular myeloperoxidase deposition that correlated significantly with eGFR and crescent formation. In vitro, AZM198 led to a significant reduction in neutrophil extracellular trap formation, reactive oxygen species production, and released human neutrophil peptide levels, and attenuated neutrophil-mediated endothelial cell damage. In vivo, delayed AZM198 treatment significantly reduced proteinuria, glomerular thrombosis, serum creatinine, and glomerular macrophage infiltration, without increasing adaptive T cell responses.ConclusionsMyeloperoxidase inhibition reduced neutrophil degranulation and neutrophil-mediated endothelial cell damage in patients with ANCA-associated vasculitis. In preclinical crescentic GN, delayed myeloperoxidase inhibition suppressed kidney damage without augmenting adaptive immune responses, suggesting it might offer a novel adjunctive therapeutic approach in crescentic GN.

scholarly journals Antioxidant and Anticancer Activities and Protein Interaction of the Oxidovanadium(IV) Naringin Complex

Inorganics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 13
Author(s):  
Andrés Gonzalo Restrepo-Guerrero ◽  
Helen Goitia-Semenco ◽  
Luciana G. Naso ◽  
Marilin Rey ◽  
Pablo J. Gonzalez ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrophobic Interactions ◽  
Biological Activities ◽  
Physicochemical Characterization ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Synthetic Procedure

The complex of oxidovanadium(IV) with naringin (Narg) [VO(Narg)2] 8H2O (VONarg) was prepared according to the literature improving the synthetic procedure and physicochemical characterization. In addition, biological activities (cytotoxic, antioxidant, and BSA interaction) were determined. The metal coordinated through the 5-hydroxy and 4-carbonyl groups of rings A and C of naringin, respectively. The antioxidant activity of VONarg, determined in vitro, was higher than those of the flavonoid against superoxide and peroxyl reactive oxygen species (ROS) and DPPH radical. The cytotoxic properties were determined by a MTT assay on adenocarcinoma human alveolar basal epithelial cells (A549). VONarg exerted a 20% decrease in cancer cells viability at 24 h incubation, while naringin and oxidovanadium(IV) cation did not show cytotoxicity. Measurements with the normal HEK293 cell line showed that the inhibitory action of the complex is selective. VONarg generated intracellular reactive oxygen species (ROS), depletion of reduced glutathione and depolarization of mitochondrial membrane potential, typical for apoptotic pathway, producing cell death by oxidative stress mechanism. Moreover, naringin interacted with bovine serum albumin (BSA) through hydrophobic interactions in a spontaneous process, and VONarg showed greater affinity for the protein but can still be transported and delivered by it (Ka 104 L·mol−1 order).

scholarly journals Role of antioxidant to protect Leydig cells induced by reactive oxygen species: a literature review

2021 ◽  
Vol 5 (1) ◽  
pp. 49
Author(s):  
Anak Agung Istri Dalem Cinthya Riris ◽  
Reny I'tishom ◽  
Siti Khaerunnisa
Keyword(s):  
Reactive Oxygen Species ◽  
Literature Review ◽  
Leydig Cells ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Reproductive Function ◽  
Protective Agent ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Male Reproductive Function

The Leydig cells play crucial role in steroidogenesis and spermatogenesis. Those processes need complex communication in hormonal and testicular to maintain male reproductive function. Abnormal condition induced by reactive oxygen species reduce cell viability through lipid peroxidation and apoptotic pathway. Antioxidant ameliorate ROS elevation and prevent cell damage. Specifically, Leydig cells are vulnerable to ROS exposure and decline its function in mediating spermatogenesis. Therefore, it is needed to improve Leydig cells viability within antioxidant supplementation. This study aimed to determine the protective effect of antioxidant on Leydig cells induced by reactive oxygen species. This type of study is a literature review. Various studies have been reviewed through critical appraisal tool Olsen-Baisch Scoring for integrated review. Furthermore, this study highlighted the importance of the mechanism of antioxidant as protective agent of Leydig cells. Supplementation of antioxidant with the correct administration, dosage, and duration is potential to balance reactive oxygen species level and protect Leydig cells.    Keywords             : Leydig cell, antioxidant, reactive oxygen species, infertility

scholarly journals XANTHENE DYES-MEDIATED IN VITRO PHOTODYNAMIC TREATMENT OF CANCER AND NON-CANCER CELL LINES

2021 ◽  
Vol 50 (3) ◽  
pp. 114-121
Author(s):  
Lukáš Malina ◽  
Kateřina Bartoň Tománková ◽  
Barbora Hošíková ◽  
Jana Jiravová ◽  
Jakub Hošík ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Rose Bengal ◽  
Antimicrobial Agents ◽  
Reactive Oxygen ◽  
In Vitro Tests ◽  
Oxygen Species ◽  
Xanthene Dyes ◽  
Erythrosin B

Rose bengal and erythrosin B are xanthene dyes mainly known and used as antimicrobial agents, but due to their photodynamic activity they are also potential photosensitizers for cancer photodynamic therapy. The aim of this work is to study a photodynamic efficacy of rose bengal and erythrosin B against human skin melanoma and mouse fibroblast cell lines, compare them with each other and find out their photodynamic properties induced by light emitting diodes with total light dose of 5 J/cm2. To fully identify and understand photodynamic properties of both potentially effective photosensitizers, a set of complex in vitro tests such as cell cytotoxic assay, measurement of reactive oxygen species production, mitochondrial membrane potential change assay, mode of cell death determination or comet assay were made. Although both photosensitizers proved to have similar properties such as increasing production of reactive oxygen species with the higher concentration, predominance of necrotic mode of death or genotoxicity, the more effective photosensitizer was rose bengal because its EC50 was over 20 times lower for both cell lines than in case of erythrosin B.  

scholarly journals 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells

2016 ◽  
Vol 113 (36) ◽  
pp. E5271-E5280 ◽  
Author(s):  
Matthias R. Bauer ◽  
Andreas C. Joerger ◽  
Alan R. Fersht
Keyword(s):  
Reactive Oxygen Species ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Target Genes ◽  
Alkylating Agents ◽  
Reactive Oxygen ◽  
Glutathione Depletion ◽  
Target Cells ◽  
Oxygen Species

The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53’s oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1MET(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

Synergistic Effect Of Nifurtimox and Inhibition Of Hsp70/Hsp90 In Treatment Of Neuroblastoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5567-5567
Author(s):  
Karin Melanie Rohrer ◽  
Gernot Bruchelt ◽  
Rupert Handgretinger ◽  
Ursula Holzer
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Heat Shock ◽  
Cell Viability ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neuroblastoma Cell Lines

Abstract Neuroblastoma is the most common solid cancer in childhood with high relapse and mortality rates. Furthermore, high risk neuroblastoma is often accompanied by an infaust prognosis. The 5-nitrofuran nifurtimox, usually used in the treatment of Chagas disease, showed cytotoxic effects against neuroblastoma in vitro and in experimental therapy, which is presumably due to the formation of oxidative stress. Inducing oxidative stress is a well investigated and suitable strategy in the treatment of malignant diseases in vitro but often encounters difficulties in clinical administration. Thus, nifurtimox as a well-established drug represents a promising new approach in treating neuroblastoma. Combining the induction of reactive oxygen species by application of nifurtimox with a blockade of the cells’ own stress response might even increase the cytotoxic effects. The chaperones heat shock protein 70 and 90 (Hsp70/Hsp90) are responsible for refolding or degrading damaged proteins, especially after stress situations such as heat or oxidative stress. Therefore, the roles of Hsp70 and Hsp90 were investigated in more detail. The commercially available human neuroblastoma cell lines IMR-32, LA-N-1 and the cell line LS, which has been established in the children’s hospital Tuebingen, were exposed to increasing doses of nifurtimox (0.070 mM to 0.348 mM) and incubated for 1, 2 or 3 days. It could be observed that cell viability of all cell lines was significantly and dose-dependently reduced (p<0.01) after nifurtimox treatment. An average reduction of cell viability by 50% was achieved after 24h incubation with 0.348 mM nifurtimox (LS and IMR-32). The assumption that nifurtimox induces the formation of reactive oxygen species could be confirmed. The amount of intracellular reactive oxygen species was significantly increased (p<0.05) in a dose-dependent manner in all cell lines after 24h. Furthermore, expression levels of heat shock proteins Hsp70 and Hsp90 were investigated. Western blot analysis revealed increased intracellular expression levels for both heat shock proteins after 24h nifurtimox treatment. Concluding that Hsp70 and Hsp90 have important roles in tumor cell survival, it was decided to specifically inhibit Hsp90. For this purpose, the neuroblastoma cell lines were treated with the geldanamycin analog 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). After inhibition of Hsp90 cells were additionally incubated with the previously used dosages of nifurtimox. A significant higher reduction of the cell viability (p<0.001) could be observed for all neuroblastoma cell lines compared to the application of nifurtimox or 17-DMAG alone. In conclusion, nifurtimox increases oxidative stress in neuroblastoma cell lines leading to significantly decreased cell viability. The specific inhibition of Hsp90 additionally intensifies this effect. The findings suggest that the combined administration of nifurtimox and the specific Hsp90 inhibitor 17-DMAG leads to a synergistic and favorable effect in the treatment of neuroblastoma. More importantly, being an approved medication and well investigated in a wide variety of clinical trials, nifurtimox and 17-DMAG are easy accessible and create a promising new approach not only in neuroblastoma treatment. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document