Administration of rHuGM-CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high-dose chemotherapy

Bile acids are synthesized in the liver, stored in gallbladder, and secreted into the intestine to aid in the absorption of lipid-soluble nutrients. In addition, bile acids also actively participate in regulation of gene expression through their ability to act as ligands for the nuclear receptor farnesoid X receptor or by activating kinase signaling pathways. Under cholestatic conditions, elevated levels of bile acids in the liver induce hepatic inflammation, and because bile acid levels are also elevated in the circulation, they might also induce vascular inflammation. To test this hypothesis, primary human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells were treated with bile acids, and the expression of ICAM-1, VCAM-1, and E-selectin were monitored. The three major bile acids found in the circulation, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, all strongly induced both the mRNA and protein expression of ICAM-1 and VCAM-1. To delineate the mechanism, the experiments were conducted in the presence of various kinase inhibitors. The results demonstrate that the bile acid-mediated induction of adhesion molecule expression occurs by stimulation of NF-κB and p38 MAPK signaling pathways through the elevation in reactive oxygen species. The bile acid-induced cell surface expression of ICAM-1 and VCAM-1 was sufficient to result in the increased adhesion of THP-1 monocytes to the HUVEC, suggesting that elevated levels of bile acids in the circulation may cause endothelium dysfunction and contribute to the initiation of early events associated with vascular lesion formation.

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Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

Cell Death and Disease ◽

10.1038/s41419-021-03449-6 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Zhuochao Liu ◽

Hongyi Wang ◽

Chuanzhen Hu ◽

Chuanlong Wu ◽

Jun Wang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Antitumor Immunity ◽

Reactive Oxygen ◽

Oxygen Species ◽

Specific Monoclonal Antibody ◽

Osteosarcoma Cells ◽

Jnk Pathway ◽

In Vivo Experiments

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

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Plant Extracts and Reactive Oxygen Species as Two Counteracting Agents with Anti- and Pro-Obesity Properties

International Journal of Molecular Sciences ◽

10.3390/ijms20184556 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4556 ◽

Cited By ~ 6

Author(s):

Hanna Zielinska-Blizniewska ◽

Przemyslaw Sitarek ◽

Anna Merecz-Sadowska ◽

Katarzyna Malinowska ◽

Karolina Zajdel ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Plant Extracts ◽

Complex Disease ◽

Reactive Oxygen ◽

Complementary Therapy ◽

Biologically Active ◽

Mitochondrial Activity ◽

Oxygen Species

Obesity is a complex disease of great public health significance worldwide: It entails several complications including diabetes mellitus type 2, cardiovascular dysfunction and hypertension, and its prevalence is increasing around the world. The pathogenesis of obesity is closely related to reactive oxygen species. The role of reactive oxygen species as regulatory factors in mitochondrial activity in obese subjects, molecules taking part in inflammation processes linked to excessive size and number of adipocytes, and as agents governing the energy balance in hypothalamus neurons has been examined. Phytotherapy is the traditional form of treating health problems using plant-derived medications. Some plant extracts are known to act as anti-obesity agents and have been screened in in vitro models based on the inhibition of lipid accumulation in 3T3-L1 cells and activity of pancreatic lipase methods and in in vivo high-fat diet-induced obesity rat/mouse models and human models. Plant products may be a good natural alternative for weight management and a source of numerous biologically-active chemicals, including antioxidant polyphenols that can counteract the oxidative stress associated with obesity. This review presents polyphenols as natural complementary therapy, and a good nutritional strategy, for treating obesity without serious side effects.

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A fluorogenic H2S donor activated by reactive oxygen species for real-time monitoring in cells and in vivo

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2021.120243 ◽

2021 ◽

pp. 120243

Author(s):

Li Li ◽

Ziqian Zhang

Keyword(s):

Reactive Oxygen Species ◽

Real Time ◽

Reactive Oxygen ◽

Oxygen Species ◽

Real Time Monitoring ◽

In Cells

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Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22147509 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7509

Author(s):

Hai Huang ◽

Jun-Koo Yi ◽

Su-Geun Lim ◽

Sijun Park ◽

Haibo Zhang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Cycle ◽

Flow Cytometry ◽

Oral Cancer ◽

Cancer Cells ◽

Reactive Oxygen ◽

Migration And Invasion ◽

Oxygen Species ◽

Oral Cancer Cells

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.

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CSIG-21. 5-ALA PDT AND TARGETING MEK/ERK SIGNALING ELICITS SYNERGISTIC ANTITUMOR EFFECTS IN DIFFUSE MIDLINE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.147 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi37-vi37

Author(s):

Gabrielle Price ◽

Daniel Rivera ◽

Alexandros Bouras ◽

Constantinos Hadjipanayis

Keyword(s):

Reactive Oxygen Species ◽

Cell Proliferation ◽

Aminolevulinic Acid ◽

Tumor Therapy ◽

Unmet Need ◽

Reactive Oxygen ◽

Oxygen Species ◽

Antitumor Effects ◽

Genetically Engineered Mouse Model

Abstract Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.

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Synthesis and evaluation of 13C-labeled 5-5-dimethyl-1-pyrroline-N-oxide aimed at in vivo detection of reactive oxygen species using hyperpolarized 13C-MRI

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2018.11.013 ◽

2019 ◽

Vol 131 ◽

pp. 18-26 ◽

Cited By ~ 2

Author(s):

Keita Saito ◽

Deepak Sail ◽

Kazutoshi Yamamoto ◽

Shingo Matsumoto ◽

Burchelle Blackman ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species ◽

Hyperpolarized 13C ◽

In Vivo Detection

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Mitochondrial Adenosine Triphosphate–regulated Potassium Channel Opening Acts as a Trigger for Isoflurane-induced Preconditioning by Generating Reactive Oxygen Species

Anesthesiology ◽

10.1097/00000542-200304000-00021 ◽

2003 ◽

Vol 98 (4) ◽

pp. 935-943 ◽

Cited By ~ 78

Author(s):

Katsuya Tanaka ◽

Dorothee Weihrauch ◽

Lynda M. Ludwig ◽

Judy R. Kersten ◽

Paul S. Pagel ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Infarct Size ◽

Adenosine Triphosphate ◽

Superoxide Anion ◽

Reactive Oxygen ◽

Oxygen Species ◽

Superoxide Anion Production ◽

Channel Opening ◽

Anion Production

Background Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo. Methods Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. Results Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent. Conclusions The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.

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