The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine

1990 ◽  
Vol 15 (11) ◽  
pp. 1101-1107 ◽  
Author(s):  
Clifford L. Eastman ◽  
Tomas R. Guilarte
Keyword(s):  
Hydrogen Peroxide ◽  
In Vitro Cytotoxicity

scholarly journals Role of polymorphic Fc gamma receptor IIIa and EGFR expression level in cetuximab mediated, NK cell dependent in vitro cytotoxicity of head and neck squamous cell carcinoma cells

2009 ◽  
Vol 58 (11) ◽  
pp. 1853-1862 ◽  
Author(s):  
Andrés López-Albaitero ◽  
Steve C. Lee ◽  
Sarah Morgan ◽  
Jennifer R. Grandis ◽  
William E. Gooding ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nk Cell ◽  
In Vitro Cytotoxicity ◽  
Carcinoma Cells ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Egfr Expression

Role of Il-2, Il-7, and IL-15 in T Cell Mediated Graft-vs-Leukemia Against Human Acute Lymphoblastic Leukemia in a NOD/scid Chimeric Mouse Model.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5256-5256
Author(s):  
Doug Cipkala ◽  
Kelly McQuown ◽  
Lindsay Hendey ◽  
Michael Boyer
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
Mouse Model ◽  
Scid Mouse ◽  
In Vitro Cytotoxicity ◽  
Scid Mouse Model

Abstract The use of cytotoxic T-lymphocytes (CTL) has been attempted experimentally with various tumors to achieve disease control. Factors that may influence GVT include CTL cytotoxicity, ability to home to disease sites, and survival of T cells in the host. The objective of our study is to evaluate the GVL effects of human alloreactive CTL against ALL in a chimeric NOD/scid mouse model. CTL were generated from random blood donor PBMCs stimulated with the 697 human ALL cell line and supplemented with IL-2, -7, or -15. CTL were analyzed for in vitro cytotoxicity against 697 cells, phenotype, and in vitro migration on day 14. NOD/scid mice were injected with 107 697 ALL cells followed by 5x106 CTL. Mice were sacrificed seven days following CTL injection and residual leukemia was measured in the bone marrow and spleen via flow cytometry. The ratios of CD8/CD4 positive T cells at the time of injection were 46/21% for IL-2, 52/31% for IL-7, and 45/14% for IL-15 cultured CTL (n=13). Control mice not receiving CTL had a baseline leukemia burden of 2.01% and 0.15% in the bone marrow and spleen, respectively (n=15). Mice treated with IL-15 cultured CTL had a reduction in tumor burden to 0.2% (n=13, p=0.01) and 0.05% (n=13, p=0.01) in bone marrow and spleen, respectively. Those treated with IL-2 or IL-7 cultured CTL showed no significant difference in leukemia burden in either the bone marrow (IL-2 1.28%, Il-7 5.97%) or spleen (IL-2 0.4%, IL-7 0.33%). No residual CTL could be identified in the bone marrow or spleen at the time of sacrifice in any CTL group. CTL grown in each cytokine resulted in similar in vitro cytotoxicity at an effector:target ratio of 10:1 (IL-2 41.3%, IL-7 37.7%, IL-15 45.3%, n=12–15, p>0.05 for all groups) and had statistically similar intracellular perforin and granzyme-B expression. In vitro CTL migration to a human mesenchymal stem cell line was greatest with IL-15 CTL (30.5%, n=4), followed by IL-7 CTL (18.9%, n=4), and least in IL-2 CTL (17.9%, n=4), though the differences were not significant. In vitro CTL migration was analyzed to an SDF-1α gradient as CXCR4/SDF-1α interactions are necessary for hematopoietic progenitor cell homing to the bone marrow. IL-15 cultured CTL showed the highest migration (48.8%, n=8) as compared to IL-2 (21.7%, n=6, p=0.048) or IL-7 CTL (35.9%, n=8, p>0.05). However, surface expression of CXCR4 measured by flow cytometry was significantly higher in IL-7 CTL (89.4%, n=9) compared to IL-2 CTL (52.2%, n=9, p<0.001) and IL-15 CTL (65.4%, n=10, p=0.002). Experiments are currently underway to further evaluate the role of CXCR4/SDF-1α in GVL. Preliminary in vivo experiments do not suggest any significant differences in CTL engraftment when evaluated at 24 hours post injection. Expression of the anti-apoptotic bcl-2 protein was greatest on IL-7 (MFI=5295, n=13) and IL-15 (MFI=4865, n=14) when compared to IL-2 CTL (MFI=3530, n=13, p=0.02 vs. IL-7, p=0.05 vs. IL-15), suggesting an increased in vivo survival ability. We hypothesize that IL-15 cultured CTL have greater GVL effects due to either higher in vivo survival, greater bone marrow homing efficiency, or both. Future experiments are planned to evaluate in vivo administration of IL-2 to enhance CTL survival in the host. In conclusion, IL-15 cultured CTL had significantly greater in vivo GVL effects compared to IL-2 and IL-7 CTL in the NOD/scid mouse model. This model can be utilized to evaluate the mechanism of T cell mediated GVL against ALL and potentially other human malignancies.

Role of cementoenamel junction on the radicular penetration of 30% hydrogen peroxide during intracoronal bleaching in vitro

1996 ◽  
Vol 12 (3) ◽  
pp. 146-150 ◽  
Author(s):  
E. Koulaouzidou ◽  
T. Lambrianidis ◽  
P. Beltes ◽  
K. Lyroudia ◽  
C. Papadopoulos
Keyword(s):  
Hydrogen Peroxide

In vitro toxicity of hydrogen peroxide against normal vs. tumor rat hepatocytes: Role of catalase and of the glutathione redox cycle

Hepatology ◽  
1988 ◽  
Vol 8 (6) ◽  
pp. 1673-1678 ◽  
Author(s):  
Philippe Mavier ◽  
Bernard Guigui ◽  
Anne-Marie Preaux ◽  
Jean Rosenbaum ◽  
Marie-Claude Lescs ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Rat Hepatocytes ◽  
In Vitro Toxicity ◽  
Redox Cycle ◽  
Glutathione Redox Cycle ◽  
Glutathione Redox

scholarly journals Role of polymorphic Fc gamma receptor IIIa and EGFR expression level in cetuximab mediated, NK cell dependent in vitro cytotoxicity of head and neck squamous cell carcinoma cells

2009 ◽  
Vol 58 (11) ◽  
pp. 1863-1864 ◽  
Author(s):  
Andrés López-Albaitero ◽  
Steve C. Lee ◽  
Sarah Morgan ◽  
Jennifer R. Grandis ◽  
William E. Gooding ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nk Cell ◽  
In Vitro Cytotoxicity ◽  
Carcinoma Cells ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Egfr Expression

scholarly journals Role of protein kinases JNK and p38 in regulation of mononuclear leucocytes apoptosis in oxidative stress

2008 ◽  
Vol 7 (3) ◽  
pp. 38-43 ◽  
Author(s):  
N. Yu. Chasovskikh
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Transmembrane Potential ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Stress Induction ◽  
Healthy Donors ◽  
Mononuclear Leucocytes

Programmed cell death of peripheral blood mononuclear leucocytes taken from healthy donors and cultivated with various concentration of Н2О2, selective inhibitors of JNK (SP600125), 38 (ML3403) and in case of pneumonia was investigated. Intensification of intracellular production of reactive oxy р МАРК - gen species was accompanied by the increase in number of apoptotic and TNFR1-presented cells and mononuclears with reduced value of mitochondrial transmembrane potential in a case of oxidative stress induction with 1 mM hydrogen peroxide and in blood taken from patients with pneumonia. Action of inhibitors SP600125 and ML3403 in vitro in oxidative stress conditions prevents the increase in number of annexin- positive mononuclear cells, that confirms the participation of JNK and 38 -kinases in mechanisms of oxidative stress-mediated apoptosis dysregulation.

scholarly journals Fibroblast Growth Factor 21 Ameliorates NaV1.5 and Kir2.1 Channel Dysregulation in Human AC16 Cardiomyocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiamin Li ◽  
Yuanshi Li ◽  
Yining Liu ◽  
Hang Yu ◽  
Ning Xu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Ventricular Arrhythmias ◽  
Sodium Current ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Serum Samples

Infarcted myocardium is predisposed to cause lethal ventricular arrhythmias that remain the main cause of death in patients suffering myocardial ischemia. Liver-derived fibroblast growth factor 21 (FGF21) is an endocrine regulator, which exerts metabolic actions by favoring glucose and lipids metabolism. Emerging evidence has shown a beneficial effect of FGF21 on cardiovascular diseases, but the role of FGF21 on ventricular arrhythmias following myocardial infarction (MI) in humans has never been addressed. This study was conducted to investigate the pharmacological effects of FGF21 on cardiomyocytes after MI in humans. Patients with arrhythmia in acute MI and healthy volunteers were enrolled in this study. Serum samples were collected from these subjects on day 1 and days 7–10 after the onset of MI for measuring FGF21 levels using ELISA. Here, we found that the serum level of FGF21 was significantly increased on day 1 after the onset of MI and it returned to normal on days 7–10, relative to the Control samples. In order to clarify the regulation of FGF21 on arrhythmia, two kinds of arrhythmia animal models were established in this study, including ischemic arrhythmia model (MI rat model) and nonischemic arrhythmia model (ouabain-induced guinea pig arrhythmia model). The results showed that the incidence and duration time of ischemic arrhythmias in rhbFGF21-treated MI rats were significantly reduced at different time point after MI compared with normal saline-treated MI rats. Moreover, the onset of the first ventricular arrhythmias was delayed and the numbers of VF and maintenance were attenuated by FGF21 compared to the rhbFGF21-untreated group in the ouabain model. Consistently, in vitro study also demonstrated that FGF21 administration was able to shorten action potential duration (APD) in hydrogen peroxide-treated AC16 cells. Mechanically, FGF21 can ameliorate the electrophysiological function of AC16 cells, which is characterized by rescuing the expression and dysfunction of cardiac sodium current (INa) and inward rectifier potassium (Ik1) in AC16 cells induced by hydrogen peroxide. Moreover, the restorative effect of FGF21 on NaV1.5 and Kir2.1 was eliminated when FGF receptors were inhibited. Collectively, FGF21 has the potential role of ameliorating transmembrane ion channels remodeling through the NaV1.5/Kir2.1 pathway by FGF receptors and thus reducing life-threatening postinfarcted arrhythmias, which provides new strategies for antiarrhythmic therapy in clinics.

Cytotoxic and Genotoxic Activities of Alkaloids from the Bulbs of Griffinia gardneriana and Habranthus itaobinus (Amaryllidaceae)

2019 ◽  
Vol 19 (5) ◽  
pp. 707-717 ◽  
Author(s):  
Eduardo R. Cole ◽  
Jean P. de Andrade ◽  
João F. Allochio Filho ◽  
Elisângela F. P. Schmitt ◽  
Anderson Alves-Araújo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Caspase 3 ◽  
Biological Activities ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Isolation And Identification ◽  
Wide Range

Background: Amaryllidaceae plants are known to be a great source of alkaloids, which are considered an extensive group of compounds encompassing a wide range of biological activities. The remarkable cytotoxic activities observed in most of the Amaryllidaceae alkaloids derivatives have prompt the chemical and biological investigations in unexplored species from Brazil. Objective: To evaluate the cytotoxic and genotoxic properties of alkaloids of Griffinia gardneriana and Habranthus itaobinus bulbs and study the role of caspase-3 as a molecular apoptosis mediator. Methods: Methanolic crude extracts of Griffinia gardneriana and Habranthus itaobinus bulbs were submitted to acid-base extraction to obtain alkaloid-enriched fractions. The obtained fractions were fractionated using chromatographic techniques leading to isolation and identification of some alkaloids accomplished via HPLC and 1H-NMR, respectively. Molecular docking studies assessed the amount of free binding energy between the isolated alkaloids with the caspase-3 protein and also calculated the theoretical value of Ki. Studies have also been developed to evaluate in vitro cytotoxicity and genotoxicity in such alkaloids and apoptosis activation via the caspase pathway using both tumor and normal cell lines. Results: Seven alkaloids were isolated and identified. Among these, 11-hydroxyvittatine and 2-α-7- dimethoxyhomolycorine were not cytotoxic, whereas tazettine, trisphaeridine, and sanguinine only showed activity against the fibroblast lineage. Lycorine and pretazettine were 10 to 30 folds more cytotoxic than the other alkaloids, including cancerous lines, and were genotoxic and capable of promoting apoptosis via the caspase-3 pathway. This result supports data obtained in docking studies wherein these two compounds exhibited the highest free energy values. Conclusion: The cytotoxicity assay revealed that, among the seven alkaloids isolated, only lycorine and pretazettine were active against different cell lines, exhibiting concentration- and time-dependent cytotoxic actions alongside genotoxic action and the ability to induce apoptosis by caspase-3, a result consistent with those obtained in docking studies.

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