High oxygen tension constricts epineurial arterioles of the rat sciatic nerve via reactive oxygen species

Microcirculation of the sheath of the rat sciatic nerve fiber was investigated by using an intravital microscope, and changes in the diameter of the epineurial arterioles in response to highly oxygenated Krebs-bicarbonate solution were evaluated. Superfusion of low-oxygen (0%) Krebs-bicarbonate solution (LKS) onto rat sciatic nerves did not affect changes in the diameter of the arterioles. Nifedipine, a Ca2+-channel blocker, caused a dose-dependent dilation of the epineurial arterioles in LKS. In contrast, superfusion of high-oxygen (21%) Krebs-bicarbonate solution (HKS) onto rat sciatic nerves significantly constricted the epineurial arterioles in a time-dependent manner. The HKS-induced constriction of the epineurial arterioles was significantly reduced by treatment with 120 U/ml superoxide dismutase (SOD) alone or 5,000 U/ml catalase alone. In the presence of 120 U/ml SOD plus 5,000 U/ml catalase, 10−4 M tempol, 10−6 M diphenyleneiodium, 2 × 10−4 M apocynin, or 10−6 M allopurinol, the HKS-induced constriction of the epineurial arterioles completely disappeared. These results suggest that superfusion of highly oxygenated solution onto rat sciatic nerves constricts the epineurial arterioles through reactive oxygen species (ROS), including superoxide and hydrogen peroxide, and that production of superoxide involves a NADPH oxidase- or xanthine oxidase-dependent pathway. In conclusion, ROS play significant roles in the regulation of microcirculation of rat sciatic nerves in vivo.

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Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish

Marine Drugs ◽

10.3390/md18060316 ◽

2020 ◽

Vol 18 (6) ◽

pp. 316 ◽

Cited By ~ 2

Author(s):

Wanchun Su ◽

Lei Wang ◽

Xiaoting Fu ◽

Liying Ni ◽

Delin Duan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Protective Effect ◽

Reactive Oxygen ◽

Saccharina Japonica ◽

Intracellular Reactive Oxygen Species ◽

Dependent Manner ◽

Hacat Cells ◽

Oxygen Species

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.

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Scavenging of Reactive Oxygen Species and Inhibition of the Oxidation of Low Density Lipoprotein by the Aqueous Extraction ofAnoectochilus formosanus

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03000692 ◽

2003 ◽

Vol 31 (01) ◽

pp. 25-36 ◽

Cited By ~ 15

Author(s):

Chun-Ching Shih ◽

Yueh-Wern Wu ◽

Wen-Chuan Lin

Keyword(s):

Reactive Oxygen Species ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Reactive Oxygen ◽

In Vivo Studies ◽

Ldl Oxidation ◽

Low Density ◽

Dependent Manner ◽

Oxygen Species

The ability of Anoectochilus formosanus extract (AFE) to react with relevant biological oxidants was evaluated in this study. In addition, its effect on oxidation of low density lipoprotein (LDL) was investigated in vitro and in vivo. AFE could scavenge reactive oxygen species, such as superoxide anion and hydroxyl radical. The study of human LDL oxidation showed that AFE delayed oxidation in a concentration-dependent manner. In vivo studies also showed that oral administration of AFE delayed the oxidation of LDL from hyperlipidemic hamsters. The ability of AFE to scavenge free radicals suggests that it may be a promising anti-atherogenic agent.

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Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90590.2008 ◽

2009 ◽

Vol 297 (5) ◽

pp. L846-L855 ◽

Cited By ~ 51

Author(s):

Shubha Murthy ◽

Andrea Adamcakova-Dodd ◽

Sarah S. Perry ◽

Linda A. Tephly ◽

Richard M. Keller ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Pulmonary Fibrosis ◽

Alveolar Macrophages ◽

Reactive Oxygen ◽

Ros Generation ◽

Dependent Manner ◽

Oxygen Species ◽

Tnf Α

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-α and ROS in a Rac1-dependent manner. TNF-α was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro . More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.

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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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