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Priscila de Souza, Karla Lorena Guarido, Karin Scheschowitsch, Luísa Mota da Silva, Maria Fernanda Werner, Jamil Assreuy, José Eduardo da Silva-Santos
We investigated long-lasting changes in endothelial and vascular function in adult rat survivors of severe sepsis induced by cecal ligation and puncture (CLP) model. For this, male Wistar rats (200-350g) had their cecum punctured once (non-transfixing hole) with a 14-gauge needle. Performed in this way, a mortality rate around 30% was achieved in the first 72h. The survivors, together with age-matched control rats (not subjected to CLP), were maintained in our holding room for 60 days (S60 group) and had the descending thoracic aorta processed for functional, histological, biochemical or molecular analyses...
September 30, 2016: Redox Biology
Shuang Chu, Xiao-Dong Mao, Li Wang, Wen Peng
Vascular endothelial dysfunction can be induced by homocysteine (Hcy) through promoted oxidative stress. Huang Qi decoction (HQD) is a traditional Chinese medical formula and its components possess antioxidant effect. The study herein was therefore designed to investigate the effects of HQD at different dosage on endothelial dysfunction induced by Hcy. Tempol and apocynin were used to investigate whether antioxidant mechanisms were involved. Endothelium-dependent relaxation of rat aortas was investigated by isometric tension recordings...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Janaina A Simplicio, Gabriel T do Vale, Natália A Gonzaga, Letícia N Leite, Ulisses V Hipólito, Camila A Pereira, Rita C Tostes, Carlos R Tirapelli
Chronic ethanol consumption is a risk factor for cardiovascular diseases. We studied whether NAD(P)H oxidase-derived reactive oxygen species (ROS) play a role in ethanol-induced hypertension, vascular dysfunction, and protein expression in resistance arteries. Male Wistar rats were treated with ethanol (20 % v/v) for 6 weeks. Ethanol treatment increased blood pressure and decreased acetylcholine-induced relaxation in the rat mesenteric arterial bed (MAB). These responses were attenuated by apocynin (30 mg/kg/day; p...
October 8, 2016: Journal of Physiology and Biochemistry
Anuj Kumar Sharma, Vikas Singh, Ruchi Gera, Mahaveer Prasad Purohit, Debabrata Ghosh
Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death...
October 6, 2016: Molecular Neurobiology
Silvia Cellone Trevelin, Célio Xavier Dos Santos, Raphael Gomes Ferreira, Larissa de Sá Lima, Rangel Leal Silva, Cristoforo Scavone, Rui Curi, José Carlos Alves-Filho, Thiago Mattar Cunha, Pérsio Roxo-Júnior, Maria-Célia Cervi, Francisco Rafael Martins Laurindo, John Stephen Hothersall, Andrew M Cobb, Min Zhang, Aleksandar Ivetic, Ajay M Shah, Lucia Rossetti Lopes, Fernando Queiroz Cunha
The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB...
October 4, 2016: Scientific Reports
Yao-Tsung Yeh, Yen-Nien Hsu, Sheng-Yun Huang, Jian-Sheng Lin, Zi-Feng Chen, Nan-Haw Chow, Shu-Hui Su, Huey-Wen Shyu, Ching-Chiang Lin, Wu-Tein Huang, Hua Yeh, Yu-Chia Chih, Yu-Hsuan Huang, Shu-Jem Su
Benzyl isothiocyanate (BITC) is a cruciferous vegetable-derived compound with anticancer properties in human cancer cells. However, its anticancer potential and underlying mechanisms remain absent in human oral cancer cells. Results indicate that BITC inhibits growth, promotes G2/M phase arrest and triggers apoptosis of OC2 cells with a minimal toxicity to normal cells. BITC-induced cell death was completely prevented by pretreatment with thiol-containing redox compounds including N-acetyl-l-cysteine (NAC), glutathione (GSH), dithiothreitol, and 2-mercaptoethanol, but not free radical scavengers mito-TEMPO, catalase, apocynin, l-NAME and mannitol...
September 28, 2016: Food and Chemical Toxicology
Yihan Zhang, Dongdong Yuan, Weifeng Yao, Qianqian Zhu, Yue Liu, Fei Huang, Jiayu Feng, Xi Chen, Yong Huang, Xinjin Chi, Ziqing Hei
Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) were determined...
2016: Oxidative Medicine and Cellular Longevity
Vikas Bhardwaj, Andela Horvat, Olga Korolkova, Kay M Washington, Wael El-Rifai, Sergey I Dikalov, Alexander I Zaika
Esophageal adenocarcinoma (EA) is one of the fastest rising tumors in the US. The major risk factor for EA is gastroesophageal reflux disease (GERD). During GERD, esophageal cells are exposed to refluxate which contains gastric acid frequently mixed with duodenal bile. This may lead to mucosal injury and Barrett's metaplasia (BE) that are important factors contributing to development of EA. In this study, we investigated DNA damage in BE cells exposed to acidic bile salts and explored for potential protective strategies...
September 21, 2016: Carcinogenesis
Xue Zhu, Ke Wang, Kai Zhang, Fanfan Zhou, Ling Zhu
Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells...
October 15, 2016: Experimental Cell Research
Sheu-Ran Choi, Soon-Gu Kwon, Hoon-Seong Choi, Ho-Jae Han, Alvin James Beitz, Jang-Hern Lee
We recently demonstrated that activation of spinal sigma-1 receptors (Sig-1Rs) induces pain hypersensitivity via the activation of neuronal nitric oxide synthase (nNOS) and NADPH oxidase 2 (Nox2). However, the potential direct interaction between nNOS-derived nitric oxide (NO) and Nox2-derived reactive oxygen species (ROS) is poorly understood, particularly with respect to the potentiation of NMDA receptor activity in the spinal cord associated with the development of central sensitization. Thus, the main purpose of this study was to investigate whether Sig-1R-induced and nNOS-derived NO modulates spinal Nox2 activation leading to an increase in ROS production and ultimately to the potentiation of NMDA receptor activity and pain hypersensitivity...
September 7, 2016: Biological & Pharmaceutical Bulletin
Barbara J Morgan, Melissa L Bates, Rodrigo Del Rio, Zunyi Wang, John M Dopp
Chronic exposure to intermittent hypoxia (CIH) elicits plasticity of the carotid sinus and phrenic nerves via reactive oxygen species (ROS). To determine whether CIH-induced alterations in ventilation, metabolism, and heart rate are also dependent on ROS, we measured responses to acute hypoxia in conscious rats after 14 and 21 d of either CIH or normoxia (NORM), with or without concomitant administration of allopurinol (xanthine oxidase inhibitor), combined allopurinol plus losartan (angiotensin II type 1 receptor antagonist), or apocynin (NADPH oxidase inhibitor)...
September 2, 2016: Respiratory Physiology & Neurobiology
Pichaya Jumnongprakhon, Piyarat Govitrapong, Chainarong Tocharus, Jiraporn Tocharus
Melatonin is a hormone that mostly produced from the pineal gland, and it performs as a strong neuroprotectant to both neuron and glial cells against methamphetamine (METH)-induced neurotoxicity. Recently, it has been found that METH also damages the blood brain barrier (BBB) structure and function. However, the protective mechanism of melatonin on the BBB impairment caused by METH has not been investigated. In this study, the primary rat brain microvascular endothelium cells (BMVECs) isolated from neonatal rats was used to investigate the protective effect of melatonin on METH-induced BBB impairment and the underlying mechanism...
November 1, 2016: Brain Research
Yoon Jeong Nam, Arum Kim, Dong Suep Sohn, Chung Soo Lee
Microbial product lipopolysaccharide has been shown to be involved in the pathogenesis of inflammatory skin diseases. Apocynin has demonstrated to have an anti-inflammatory effect. However, the effect of apocynin on the Toll-like receptor-4-dependent activation of Akt, mammalian target of rapamycin (mTOR), and nuclear factor (NF)-κB pathway, which is involved in productions of inflammatory mediators in keratinocytes, has not been studied. Using human keratinocytes, we investigated the effect of apocynin on the inflammatory mediator production in relation to the Toll-like receptor-4-mediated-Akt/mTOR and NF-κB pathways, which regulates the transcription genes involved in immune and inflammatory responses...
September 2, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
C M Rosa, R Gimenes, D H S Campos, G N Guirado, C Gimenes, A A H Fernandes, A C Cicogna, R M Queiroz, I Falcão-Pires, D Miranda-Silva, P Rodrigues, F R Laurindo, D C Fernandes, C R Correa, M P Okoshi, K Okoshi
PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM)...
2016: Cardiovascular Diabetology
Wenhong Deng, Ablikim Abliz, Sheng Xu, Rongze Sun, Wenyi Guo, Qiao Shi, Jia Yu, Weixing Wang
Recent studies demonstrated that apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor, significantly decreased acute pancreatitis‑associated inflammatory and oxidative stress parameters. In addition, apocynin was able to reduce ischemic reperfusion injury‑associated damage; however, the exact effects of apocynin on acute pancreatitis‑associated intestinal mucosal injury have yet to be fully clarified. The present study aimed to investigate the protective effects of apocynin on intestinal mucosal injury in a rat model of severe acute pancreatitis (SAP)...
October 2016: Molecular Medicine Reports
Agostino Virdis, Marco Gesi, Stefano Taddei
Reactive oxygen species (ROS) are generated by cell metabolism of oxygen and represent signaling molecules playing an active role in vascular biology. In pathological conditions, including hypertension, a ROS excess, together with reduced endogenous antioxidant defenses, occurs, determining a state of oxidative stress. NAD(P)H oxidase (Nox) is a major ROS source within the vasculature. A large body of literature has demonstrated that hypertension-associated vascular functional and structural changes are attributable to Nox-driven intravascular ROS generation...
August 25, 2016: Vascular Pharmacology
Murat Atabey Ozer, Nihat Polat, Serkan Ozen, Tevfik Ogurel, Hakan Parlakpinar, Nigar Vardi
The aim of the current study was to evaluate the effect of apocynin (APO) on the development of proliferative vitreoretinopathy (PVR). New Zealand-type male rabbits were randomly grouped into three as follows: (1) Sham group rabbits which were applied intraperitoneal (i.p.) vehicle without PVR; (2) PVR group rabbits where PVR was created and an i.p. vehicle was administered for 21 successive days; (3) PVR + APO group rabbits where PVR was created and i.p. APO was administered for 21 successive days. Fundus examination was conducted with an indirect ophthalmoscope before starting the experiments and at each visit afterwards...
August 5, 2016: International Ophthalmology
Minu Sharma, Amit Sud, Tanzeer Kaur, Chanderdeep Tandon, S K Singla
Diminished mitochondrial activities were deemed to play an imperative role in surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is particularly valuable to delineate the damaging effects of oxidative stress on mitochondrial proteins. The present study was designed to apply large-scale proteomics to describe systematically how mitochondrial proteins/pathways govern the renal damage and calcium oxalate crystal adhesion in hyperoxaluria. Furthermore, the potential beneficial effects of combinatorial therapy with N-acetylcysteine (NAC) and apocynin were studied to establish its credibility in the modulation of hyperoxaluria-induced alterations in mitochondrial proteins...
September 2016: Free Radical Research
Young-Jae Hwang, Sung Joon Lee, Jin-Young Park, Wanjoo Chun, Seung-Joo Nam, Jin Myung Park, Sung Chul Park, Dae Hee Choi, Chang Don Kang
Apocynin, an inhibitor of NADPH oxidase, exhibits anti-inflammatory properties in ulcerative colitis. However, the underlying mechanism by which apocynin exerts this effect has not been clearly demonstrated. The objective of this study was to elucidate the anti-inflammatory mechanism of apocynin in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. Apocynin inhibited LPS-induced extracellular secretion of the pro-inflammatory mediators, nitric oxide (NO) and PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2...
September 2016: Drug Development Research
Wenbin Ye, Zhaoming Zhong, Siyuan Zhu, Shuai Zheng, Jun Xiao, Shaolian Song, Hui Yu, Qian Wu, Zhen Lin, Jianting Chen
Advanced oxidation protein products (AOPPs) have been shown to participate in the progression of rheumatoid arthritis (RA). However, the effect of AOPPs accumulation on catabolic effect in human chondrocyte and the underlying mechanism(s) remain unclear. The present study demonstrated that AOPPs inhibited cell viability and glycosaminoglycan (GAG) production in human chondrocyte. Exposure of chondrocyte to AOPPs significantly increased the production of catabolic factors, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMPs)-3 and MMP-13...
October 2016: International Immunopharmacology
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