The selective NADPH oxidase inhibitor apocynin has potential prophylactic effects on melamine-related nephrolithiasis in vitro and in vivo

2014 ◽  
Vol 399 (1-2) ◽  
pp. 167-178 ◽  
Author(s):  
Xiaoran Li ◽  
Jianzhong Lu ◽  
Panfeng Shang ◽  
Junsheng Bao ◽  
Zhongjin Yue
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Nadph Oxidase Inhibitor

scholarly journals Antioxidant protection by PECAM-targeted delivery of a novel NADPH-oxidase inhibitor to the endothelium in vitro and in vivo

2012 ◽  
Vol 163 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Elizabeth D. Hood ◽  
Colin F. Greineder ◽  
Chandra Dodia ◽  
Jingyan Han ◽  
Clementina Mesaros ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Targeted Delivery ◽  
Oxidase Inhibitor ◽  
Antioxidant Protection ◽  
Nadph Oxidase Inhibitor

scholarly journals DUOX2 is a Generator of ROS in the Ovary and a Potential Mediator of Ovulation

2020 ◽  
Author(s):  
Gil M Yerushalmi ◽  
Yuval Yung ◽  
Oranit Saiagh Dayan ◽  
Ettie Maman ◽  
Sarit Avraham ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Granulosa Cells ◽  
Fertility Control ◽  
Oxidase Inhibitor ◽  
Signaling Cascades ◽  
Nadph Oxidase Inhibitor ◽  
Ovulatory Process

Abstract Background: Ovulation is triggered by the preovulatory surge of the pituitary luteinizing hormone (LH). LH/hCG induction of reactive oxygen species (ROS) is required for successful ovulation. H2O2, one of ROS species, was shown to fully mimic the effect of LH/hCG in mice ovulation. However, the molecular process that generates H2O2 in the ovary during ovulation remains largely unknown. DUOX2, a member of the NOX/DUOX family of NADPH oxidase, is capable of generating H2O2. Results: Using global transcriptome RNAseq, we identified that DUOX2 is one of the transcripts that was markedly upregulated in granulosa cells during ovulation. Treatment with human chorionic gonadotropin (hCG), an ovulatory trigger, significantly increases the expression of DUOX2 mRNA and protein in human GCs both in vivo and in vitro. hCG-induced up-regulation of DUOX2 is mediated by the cAMP-PKA and the PKC pathway. A functional test reveals that DUOX2 chemical inhibitor, Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, decreased H2O2 levels in MGCs (Mural Granulosa Cells) treated with hCG. The inhibition of H2O2 by DPI suggests that DUOX2 activity is required for hCG-induced elevation of extracellular H2O2 in MGCs. In vivo treatment of mice with DPI significantly decreases the number of ovulated oocytes and markedly attenuates the expression of key ovulatory genes. These results support the putative role of DUOX2 in ovulation. Conclusions: DUOX2 is a ROS generator during the ovulatory process and is involved in the LH/hCG-induced signaling cascades leading to ovulation. Treatment with DUOX2 inhibitors may affect late folliculogenesis and ovulation and thus may serve for fertility control.

scholarly journals Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification

2021 ◽  
Vol 22 (22) ◽  
pp. 12277
Author(s):  
En-Shao Liu ◽  
Nai-Ching Chen ◽  
Tzu-Ming Jao ◽  
Chien-Liang Chen
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Calcification ◽  
Wistar Rats ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidase Inhibitor ◽  
In Vivo Studies ◽  
Ros Production

Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium–induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium–induced VSMC calcification process (p < 0.05). The protective effect of DXM in calcified-medium–induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.

scholarly journals Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 482
Author(s):  
Seul Gee Lee ◽  
Jaeok Lee ◽  
Kyung Min Kim ◽  
Kee-In Lee ◽  
Yun Soo Bae ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Oxidase Inhibitor ◽  
High Concentration ◽  
Time Curve ◽  
Suitable Candidate ◽  
Nadph Oxidase Inhibitor ◽  
Concentration Time ◽  
Zero Time

In a previous study, the specific NOX1/2/4 inhibitor Ewha-18278 was confirmed as a possible treatment for osteoporosis both in vitro and in vivo. Here, we investigated the pharmacokinetics (PK) of the compound by intravenous (IV) and oral administrations to rats. Dimethyl sulfoxide (DMSO)-based and diazepam injection-based formulations were used to dissolve the compound. In the latter formulation applicable to humans, the changes in PK parameters were monitored at two different concentrations (1 mg/mL and 2 mg/mL). The area under the plasma concentration-time curve from zero time to infinity (AUCinf) of Ewha-18278 was highest in the DMSO-based formulation (2 mg/mL). Also, the concentration was increased 1.6-fold at the low concentration of the diazepam injection-based formulation compared to the high concentration. There was no statistical significance in the AUCinf of the compound between DMSO-based formulation (2 mg/mL) and diazepam injection-based formulation (1 mg/mL). These results suggest that Ewha-18278 can be delivered to humans by both IV and oral routes. In addition, the diazepam injection-based formulation of Ewha-18278 appears to be a suitable candidate for dosage development for future toxicity test and clinical trial.

scholarly journals Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hongzhen Li ◽  
Chunyan Peng ◽  
Chenhui Zhu ◽  
Shuang Nie ◽  
Xuetian Qian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Nadph Oxidase ◽  
Western Blot ◽  
Cancer Progression ◽  
Histone Methylation ◽  
Invasion And Metastasis ◽  
Independent Manner ◽  
Nadph Oxidase 4

Abstract Background Hypoxia is a characteristic of the tumor microenvironments within pancreatic cancer (PC), which has been linked to its malignancy. Recently, hypoxia has been reported to regulate the activity of important carcinogenic pathways by changing the status of histone modification. NOX4, a member of NADPH oxidase (NOX), has been found to be activated by hypoxia and promote cancer progression in several cancers. But whether it is involved in the epigenetic changes of tumor cells induced by hypoxia is still unclear, and its biological roles in PC also need to be explored. Methods A hypoxic-related gene signature and its associated pathways in PC were identified by analyzing the pancreatic cancer gene expression data from GEO and TCGA database. Candidate downstream gene (NOX4), responding to hypoxia, was validated by RT-PCR and western blot. Then, we evaluated the relationship between NOX4 expression and clinicopathologic parameters in 56 PC patients from our center. In vitro and in vivo assays were preformed to explore the phenotype of NOX4 in PC. Immunofluorescence, western blot and chromatin immunoprecipitation assays were further applied to search for a detailed mechanism. Results We quantified hypoxia and developed a hypoxia signature, which was associated with worse prognosis and elevated malignant potential in PC. Furthermore, we found that NADPH oxidase 4 (NOX4), which was induced by hypoxia and upregulated in PC in a HIF1A-independent manner, caused inactivation of lysine demethylase 5A (KDM5A), increased the methylation modification of histone H3 and regulated the transcription of EMT-associated gene_ snail family transcriptional repressor 1 (SNAIL1). This served to promote the invasion and metastasis of PC. NOX4 deficiency repressed hypoxia-induced EMT, reduced expression of H3K4ME3 and impaired the invasion and metastasis of PC cells; however, knockdown of KDM5A reversed the poor expression of H3KEME3 induced by NOX4 deficiency, thereby promoting EMT. Conclusions This study highlights the prognostic role of hypoxia-related genes in PC and strong correlation with EMT pathway. Our results also creatively discovered that NOX4 was an essential mediator for hypoxia-induced histone methylation modification and EMT in PC cells.

scholarly journals Intermittent Hypoxia Affects the Spontaneous DifferentiationIn Vitroof Human Neutrophils into Long-Lived Giant Phagocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Larissa Dyugovskaya ◽  
Slava Berger ◽  
Andrey Polyakov ◽  
Peretz Lavie ◽  
Lena Lavie
Keyword(s):  
Nadph Oxidase ◽  
Intermittent Hypoxia ◽  
Oxidase Inhibitor ◽  
Human Neutrophils ◽  
Hypoxic Conditions ◽  
Oxygen Conditions ◽  
Extended Lifespan ◽  
First Time ◽  
Dose Dependent

Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ) which spontaneously developin vitrowithout additional growth factors or cytokines. Gϕare CD66b+/CD63+/MPO+/LC3B+and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS) production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕformation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH) (29 cycles/day for 5 days) completely abolished Gϕformation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles) decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phoxexpression, whereas under 24 h sustained hypoxia (SH) the size and expression of LC3B and gp91-phox/p22-phoxresembled Gϕformed in normoxia. Diphenyl iodide (DPI), a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕformation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC) abrogated the effects of IH by inducing large CD66b+/LC3B+Gϕand increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕdevelopment.

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